The findings, published in Cell Metabolism, suggest that the protein, called PD-L2, could serve as a target for treatments designed to remove harmful aging cells or as a blood marker that helps researchers track them.

“Our findings suggest that PD-L2 may help aging cells stay in the body when they would normally be removed by the immune system,” said Selim Chaib, PhD, research assistant professor of Medicine at Cedars-Sinai and first and co-corresponding author of the study.

These harmful aging cells, called senescent cells, become damaged and stop dividing but do not die. The cells remain in tissues and release substances that promote inflammation and interfere with the function of nearby cells. Their buildup has been linked to age-related health problems.

Investigators found that in laboratory mice, removing or blocking PD-L2 reduced the number of aging cells and levels of the inflammatory substances they produce. The mice were better able to process sugar and could grip objects with greater strength.

Investigators also found that human aging cells produced more PD-L2 than younger cells, and levels of the protein increased in some human tissues with age.

“If we can find a way to block this protein, we may be able to help the immune system get rid of these cells and potentially improve health problems linked with aging,” said James Kirkland, MD, PhD, director of the Center for Advanced Gerotherapeutics and senior author of the study.

Future research will explore whether blocking PD-L2 can safely produce health benefits in human patients and help researchers better understand its role in age-related diseases.

Additional Cedars-Sinai authors include Larissa Langhi Prata, Masayoshi Suda, Andres Sola, Jia Nie, Hyungsoo Kim, Tamar Pirtskhalava, Nino Giorgadze, Nicolas Musi, Ze’ev Ronai, and Tamara Tchkonia.

Other authors include Thomas Mitchell, Zacharias Anastasiadis, Hawley Kunz, Stella Victorelli, Ricardo Lozano Flores, Moritz Weigl, Shimpei Kawamoto, Ken Uemura, Binsheng Wang, Christina Inman, Ailing Xue, Kurt Johnson, Jair Espindola-Netto, Sonja Suvakov, Jennet Hatamova, Erik Parker, Davyn Benitto Hartono, Vagisha Kulshreshtha, Jose Alberto Lopez-Dominguez, Aaron Deisinger, Allyson Palmer, Yi Zhu, Megan Weivoda, Anne Gingery, Robert Hromas, Vesna Garovic, João Passos, David Allison, Eiji Hara, Michael Jensen, Stefan Tullius, Manuel Serrano, Ming Xu, Ian Lanza, and Yuji Ikeno.

Funding: Work in the J.L.K. laboratory was supported by the US National Institutes of Health (NIH; grants R37AG013925, R33AG061456, and P01AG062413), the Connor Fund, Robert J. and Theresa W. Ryan, the Hevolution Foundation, and the Noaber Foundation. Y.I. was supported by the San Antonio Nathan Shock Center Pathology Core (NIH Grant P30AG13319), San Antonio Claude D. 445 Pepper Center (NIH P30 AG044271), and NIH grants R01AG070034 and R56AG057785. M.D.J.’s studies were supported by NIH grants DK-45343 and DK-40484. H.E.K. was supported by an NIH musculoskeletal research training grant (T32AR56950) and NIH grant K01DK134765. S.K. was supported by the Japan Science and Technology Agency (JST) JPMJFR2308 and Japan Society for the Promotion of Science (JSPS) JP23K06481. L.G.P.L.P was supported by NIH grant 1K01AG090692. The clinical trial (NCT03350906) was supported by grants UL1TR002377 from the National Center for Advancing Translational Sciences (NCATS) and NIH R01AG054454. Y.Z. was supported by the Hevolution Foundation. J.F.P. was supported by NIH grants R01AG068048, R01AG82708, and UG3CA268103 and the Glenn Foundation for Medical Research. S.V.G. is supported by a Robert and Arlene Kogod Center on Aging Career Development Award and a c-SiG Pilot and Feasibility Award. A.G. was supported by NIH grant R01AR076347. M.X. is supported by a Hevolution/AFAR New Investigator Award in Biology and Geroscience Research. This work was supported in part by NIH P30AG050886.

Disclosures: S.C. holds patents or pending patents on PD-L2 at Mayo Clinic and Spanish National Cancer Research Center, some of which had been licensed to Rejuveron Senescence Therapeutics. M.S. is a shareholder of Senolytic Therapeutics, Life Biosciences, Rejuveron Senescence Therapeutics, and Altos Labs. T.T., Y.Z., A.K.P., T.P., N.G., and J.L.K. have a financial interest related to this research, including patents and pending patents covering senolytic drugs and their uses that are held by Mayo Clinic.

Cedars-Sinai Health Sciences University is advancing groundbreaking research and educating future leaders in medicine, biomedical sciences and allied health sciences. Learn more about the university.

Systemic sclerosis, also called scleroderma, is a chronic, life-threatening condition that scars the skin, lungs, heart and other organs. Because there is no cure or known cause for the disease, which affects about 100,000 people in the U.S., treatments focus on relieving symptoms.

“That’s why we are so excited about our findings,” said Eduardo Marbán, MD, PhD, executive director of the Smidt Heart Institute at Cedars-Sinai and corresponding author of the study. “The basic immune system pathway driving systemic sclerosis is blocked by this new drug, making it a potential future therapy.”

Investigators tested the experimental drug, called TY1, on immune cells collected from patients with systemic sclerosis. They found that the drug reduced inflammation and DNA damage in those cells. When they administered TY1 to laboratory mice with a condition that mimics systemic sclerosis, investigators found that heart function and physical activity improved, and scar formation in organs was reduced.

TY1, which was developed at Cedars-Sinai, is a synthetic version of a type of noncoding ribonucleic acid (RNA), a molecule that regulates cellular processes. After using TY1 to reduce tissue damage in laboratory experiments addressing heart attacks, as reported last year, investigators sought to determine if TY1 might have a similar effect on autoimmune disorders.

“We chose to test TY1 in systemic sclerosis because the science of how the drug works makes sense and also because it is such a devastating disease,” said Ahmed Ibrahim, PhD, MPH, associate professor of Cardiology at Cedars-Sinai and a co-investigator of the study.

Investigators are currently preparing an investigational new drug application to the U.S. Food and Drug Administration, the first step toward obtaining approval for studying TY1 in people with systemic sclerosis.

"This innovative study illustrates how doing careful research on one disease can lead to key discoveries on another — in this case, from conditions that can stiffen the heart to scleroderma, a rare disease that hardens the skin and internal organs in patients who have waited decades for better treatment options,” said Susan Cheng, MD, chair of the Department of Cardiology in the Smidt Heart Institute.

Additional Cedars-Sinai authors include Salwa Soussi, Alessandra Ciullo, Kara Tsi, Weixin Liu, Liang Li, Mario Fournier, Thassio Mesquita, Alberto Marchevsky, Nunzio Bottini and Francesco Boin.

Xaviar Jones, MD, is the first author of the paper and is currently completing his residency training at Yale University.

Funding: This work is the result of National Institutes of Health funding, in whole or in part, and is subject to the NIH Public Access Policy. Through acceptance of this federal funding, the NIH has been given a right to make the work publicly available in PubMed Central. Supported funding for this study include grants NIH (R01HL164588 to EM, and T32HL116273 to EM, which supported XMJ), and the California Institute for Regenerative Medicine (TRAN1-15317 to AGI).

Disclosures: EM owns founder’s equity in Capricor. AI owns stock in Capricor. Capricor has no relationship with this project, nor any licensing rights to the discoveries reported here. All other authors declare no competing interests.

Cedars-Sinai Health Sciences University is advancing groundbreaking research and educating future leaders in medicine, biomedical sciences and allied health sciences. Learn more about the university.

A new study led by Cedars-Sinai Health Sciences University investigators found that prostate-specific antigen (PSA) levels in the blood, which are used to track the effectiveness of prostate cancer treatment, need to be 10 times lower than most physicians generally target for the best patient outcomes.

The study, published in Cancer, could help doctors better manage treatment of prostate cancer patients, maximizing patients’ chances of survival.

“PSA levels drop dramatically when patients receive hormone therapy,” said Stephen Freedland, MD, professor of Urology and director of the Center for Integrated Research in Lifestyle and Cancer at Cedars-Sinai, and first author of the study. “Our study found that the optimal PSA level was less than 0.2 nanograms per milliliter of blood. However, fewer than half of patients given hormone therapy alone reached that optimal level for overall survival.”

Investigators reviewed Veterans Health Administration data on 4,090 prostate cancer patients. They found that even if PSA dropped 90%, if it did not get below 0.2 nanograms per milliliter of blood, outcomes were not good.

Importantly, the study found that if doctors added drugs called androgen receptor pathway inhibitors to their hormone therapy, patients were much more likely to reach PSA levels below 0.2 nanograms per milliliter of blood.

“Many physicians don’t offer patients additional treatment because hormone therapy alone lowers their PSA levels below 2 nanograms per milliliter, which we previously showed was many physicians’ target level,” Freedland said. “We hope these data will change that practice.”

Additional authors include Wei Gao, PhD; Maëlys Touya, PharmD, MSc; Hongbo Yang, PhD; David Russell, MD, FACS; Jingyi Chen, MS; Grace Chen, MS; and Jasmina I. Ivanova, MA.

Funding: Sponsored by Pfizer Inc. and Astellas Pharma Inc.

Disclosures: Stephen J. Freedland reports consulting or advisory roles with Astellas Pharma Inc., AstraZeneca, Bayer, Candel, Eli Lilly, Johnson & Johnson Innovative Medicine (formerly Janssen), Merck, Novartis, Pfizer Inc., Sanofi, Sumitomo Pharma America, Inc. (formerly Myovant Sciences), and Tolmar.

New Tool Measures Thyroid Cancer Patients’ Anxiety

A new tool created by Cedars-Sinai Health Sciences University investigators is the first to measure anxiety in patients with thyroid cancer. Described in Thyroid, the Thyroid Cancer Modified Anxiety Scale (TC-MAX) could help doctors clarify patients’ expectations, better match their treatment to their needs, and improve patient outcomes.

“A patient’s distress greatly influences which thyroid cancer treatment the patient prefers and what their doctor recommends,” said Allen Ho, MD, professor of Surgery, co-director of the Thyroid Cancer Program at Cedars-Sinai Cancer and senior author of the study. “We found that our tool effectively assesses patient concerns to help doctors better determine the best course of treatment. This is especially important when the treatment options have similar likely outcomes but patient preferences vary widely.”

The tool includes 18 questions that measure a patient’s general cancer-related anxiety, their anxiety around ultrasound testing, which is used to monitor thyroid cancer progression, and their fear about whether their cancer will progress or come back. Investigators created TC-MAX in collaboration with Thyroid Cancer Survivors’ Association, the world’s largest thyroid cancer patient consortium. They relied on medical literature, physician expertise and the perspectives of more than 1,000 thyroid cancer patients.

The study showed that the extent of each patient’s anxiety mirrored the extent of surgery they chose, Ho said. When active surveillance, partial thyroid removal and total thyroid removal were all options, patients with the highest TC-MAX anxiety scores chose to have their entire thyroid removed, while those with lower average TC-MAX scores generally selected partial thyroid removal. Patients with the lowest scores chose active surveillance.

Ho said that the tool is now ready for use in clinical trials and patient care.

Additional Cedars-Sinai authors include Amanda J. Bastien MD, Sungjin Kim MS, Cynthia Zalt, Iris Cong PhD, Jewel Ng, Caroline Marshall, Christopher V. Almario MD MSHPM, Omer Liran MD, Brennan M.R. Spiegel MD, MSHS, Jon Mallen-St. Clair MD, PhD, Evan Walgama MD, Kevin S. Scher MD, Julie K. Jang MD, Yufei Chen MD, Samuel Zhang MD, Linnea Peterson MD, Wendy L. Sacks MD, and Zachary S. Zumsteg MD.

Other authors include Gary Bloom and Michelle M. Chen MD.

Funding: AAOHNS CORE Grant; Cedars-Sinai Jim and Eleanor Randall Department of Surgery Research Award.

Reducing Unnecessary Fluid Testing Could Lower Cancer Care Costs

Doctors might be able to safely reduce healthcare costs by skipping unnecessary laboratory tests for patients with advanced gynecologic cancers, according to a Cedars-Sinai Health Sciences University study. The paper, published in JAMA Network Open, examined testing on fluid drained from the abdomen or around the lungs.

Patients with advanced gynecologic cancer often experience fluid buildup in these areas. Draining the fluid helps relieve pain, pressure and other symptoms, but the investigators found that laboratory testing of the fluid is frequently unnecessary.

Cedars-Sinai gynecologic oncology fellow Yingao Zhang, MD, and obstetrics and gynecology resident Olivia Foy, MD, are co-first authors of the study.

“We undertook this study to determine how often unnecessary tests may be safely skipped, and to estimate how much this would help reduce healthcare costs,” Zhang said.

Investigators reviewed 976 fluid-draining procedures performed on gynecologic cancer patients at one hospital over 10 years. Laboratory testing was ordered in 40% of cases, a common practice done to rule out infection, check for the presence of cancer cells, and determine the cause of fluid buildup.

Nearly 80% of those orders included at least one test the researchers determined was likely unnecessary—either because a cancer diagnosis had already been confirmed or a patient had no symptoms that would prompt further fluid testing. The estimated cost of these tests was roughly $1million over 10 years.

The investigators found that unnecessary tests were more likely to be ordered in the emergency department or for hospitalized patients than in outpatient clinics. They also found that non-oncology care providers were more likely to order unneeded fluid tests than oncologists.

“Avoiding automatic lab testing on fluid from patients with known cancer diagnoses represents a low-risk opportunity to reduce healthcare costs,” Foy said.

The investigators identified clinician education as a way to reduce unnecessary testing and related costs, and suggested that similar analyses in other cancer types and other institutions could uncover additional cost-reducing opportunities.

Additional Cedars-Sinai authors include Grace Pipes, MD; and Margaret I. Liang, MD, MSHPM.

Funding: The Cedars-Sinai Honest Enterprise Research Broker (HERB) Committee, which assisted with cohort building, is supported by the NIH National Center for Advancing Translational Science (NCATS) UCLA CTSI Grant Number UL1TR001881.

Disclosures: Dr. Liang reported grants from Merck, grants from Foundation for Women’s Cancer, and personal fees from Association of Cancer Care Centers outside the submitted work.

How Your Brain Stays Focused on a Goal

Cedars-Sinai Health Sciences University investigators have discovered how the brain maintains focus when a person is working toward a goal. The study, published in Nature Human Behaviour, sheds light on how a person’s brain actively maintains task goals in working memory while that person responds to changes in their environment.

“Our findings show that the brain maintains memories of task goals by keeping certain neurons persistently active over minutes,” said Ueli Rutishauser, PhD, professor of Neurosurgery, at Cedars-Sinai and senior author of the study. “The two different brain regions we studied maintained such memories in two different formats, thereby giving people the flexibility to adapt while continuing to pursue the same goal.”

The study concentrated on two brain regions: the medial frontal cortex, which supports planning, decision-making and long-term goal achievement, and the hippocampus, which plays an important role in learning and memory.

Investigators recorded the activity of individual brain cells while study participants completed tasks designed to test how the brain remembers goals over many minutes without reminders.

By analyzing activity patterns in different brain regions, investigators found that task goals are stably and persistently represented by brain cells in the medial frontal cortex many minutes after instructions were given to the participants. In contrast, the hippocampus continuously updated task goal information as circumstances changed on the timescale of seconds. This allows a person to adapt quickly to change without losing sight of a desired long-term outcome.

Additional Cedars-Sinai authors include Hristos Courellis, Michael Kyzar, Juri Minxha and Adam Mamelak.

Other authors include Araceli R. Cardenas, Taufik Valiante and Ralph Adolphs.

Funding: This work was supported by the BRAIN Initiative through the NIH Office of the Director (U01NS117839 to U.R.), the Simons Foundation Collaboration on the Global Brain (to U.R. and R.A.), and by a merit scholarship from the Josephine De Karman Fellowship Trust (to H.S.C.).

Small Bowel Microbiome Offers Clues to Women’s Health        

A new study by investigators at Cedars-Sinai Health Sciences University has identified differences in the makeup and organization of the small bowel microbiome between women and men. The findings, published in iScience, could offer new insights into why some conditions are more prevalent in women.

The small bowel microbiome comprises a community of microorganisms that coexist in this part of the digestive tract and play vital roles in immune function, metabolism and hormonal regulation.

“One intriguing finding was a bacterial community containing Granulicatella, which we found only in women,” said Ruchi Mathur, MD, director of Clinical Research and Clinical Operations for the Medically Associated Science and Technology (MAST) Program at Cedars-Sinai and corresponding author of the study. “Bacteria in this community appear at increased levels in women with polyendocrine metabolic ovarian syndrome, formerly known as polycystic ovary syndrome.”

Investigators also found sex differences related to how small bowel microbes produce fructans, complex carbohydrates known for triggering digestive symptoms in irritable bowel syndrome (IBS), a condition far more common in women than men.

“Our findings show that biological sex is a critical variable in the small bowel microbiome,” said Mathur, also a professor of Medicine. “We must consider it as we move toward more personalized approaches to understanding and treating disease.”

Other Cedars-Sinai authors include Mohamad Rashid, Gabriela Leite, Gillian M. Barlow, Ava Hosseini, Daniel Brimberry, Dilara Flor, Gonzalo Parodi, Maritza Sanchez, Ignacio Rivera, Angel Trujillo, Maria Jesus Villanueva-Millan, Walter Morales, Stacy Weitsman and Mark Pimentel.

Funding: This study was supported by the Monica Lester Charitable Trust and the Elias, Genevieve and Georgianna Atol Charitable Trust in support of Ruchi Mathur’s research, and the National Philanthropic Trust in support of Mark Pimentel’s research.

Boosting the Accuracy of Disease Risk Prediction From Genetic Data

Investigators at Cedars-Sinai Health Sciences University have developed a new computational framework for improving how genetic data is used to estimate the inherited risk that an individual will develop conditions like Alzheimer's disease, Type 2 diabetes, high blood pressure and breast cancer.

The framework, called Adaptive Boosting of Pre-trained Polygenic Risk Scores (AB-PRS) and described in Nature Communications, builds on existing polygenic risk scores, tools that estimate disease risk based on many genetic variants across the genome, and identifies additional genetic signals that may not be fully captured by current scoring methods.

"As more people undergo genetic testing, it's becoming increasingly important to make the best use of that information," said Ruowang Li, PhD, co-corresponding author of the study and assistant professor of Computational Biomedicine at Cedars-Sinai. "Our findings aim to improve the accuracy of genetic risk prediction, allowing us to better predict disease risk and guide more personalized care."

Polygenic risk scores are increasingly used in research and clinical settings to estimate genetic susceptibility to common diseases, but their accuracy varies across diseases, datasets and populations. Investigators trained AB-PRS to identify genetic signals that existing risk scores may miss. They tested the approach using genetic data from the UK Biobank and validated the findings in three independent biobanks. The method consistently matched or outperformed existing polygenic risk scores across multiple diseases. The researchers say additional validation, particularly in more diverse populations, will be needed before the approach can be widely used in clinical care.

Additional Cedars-Sinai authors include Raelynn Chen, Olivia Wu, Okan Bilge Ozdemir, Zaldy Tan.

Other authors include Jie Hu, Maxwell Salvatore, Yiwen Lu, Shawn Murphy, Elizabeth Karlson, Atlas Khan, Krzysztof Kiryluk, Iftikhar Kullo, Johanna Smith, Eimear Kenny, Yuan Luo, William G. La Cava, Marylyn D. Ritchie and Yong Chen.

Funding: J.H. and Y.C.’s efforts were supported in part by National Institutes of Health

(U01TR003709, RF1AG077820, R01AG073435, R01DK128237). R.L. is supported

by the National Institutes of Health grants R01 AG094962, P30 AG094848 and U01 AG066833 and in part by Cedars-Sinai Department of Neurology/Jona Goldrich Center for Alzheimer’s & Memory Disorders. R.C. and O.B.O. are supported by the Department of Computational Biomedicine, Cedars-Sinai.

Cedars-Sinai Health Sciences University is advancing groundbreaking research and educating future leaders in medicine, biomedical sciences and allied health sciences. Learn more about the university.

Atrial fibrillation, or AFib, is a condition in which the heart’s upper chambers beat irregularly, often causing a rapid heartbeat. Some people with AFib also experience chest discomfort, shortness of breath or heart palpitations. Others may notice only mild fatigue during activity. And still others may feel no symptoms at all. AFib also increases the risk of stroke.

“That’s why it’s especially important to carefully manage AFib in the summer, when people may spend more time in the sun, lose fluids through sweating, and drink more alcohol on vacation, at barbecues and at other outdoor social gatherings,” said Archana Ramireddy, MD, a clinical electrophysiologist in the Smidt Heart Institute. “Older adults are especially affected by the heat, even if it may not seem obvious at first.”

In recognition of AFib Awareness Month in September—when Southern California often experiences some of its hottest weather—the Cedars-Sinai Newsroom spoke with Ramireddy about steps people with AFib can take to stay healthy.

What summer factors can trigger an AFib episode?

Hot weather can put added stress on the heart, but heat itself isn’t necessarily the primary concern. Dehydration is of special concern because people lose fluids through sweating. Older adults may be particularly susceptible to heat-related dehydration because the body’s ability to conserve fluids and regulate temperature can decline with age. Alcohol is another concern because it is a well-recognized trigger for AFib, and people tend to drink more during the summer while vacationing, spending time outdoors and attending social gatherings.

Should people with AFib drink plain water to stay hydrated, or do they need electrolytes?

Plain water is usually the best choice. Electrolyte drinks may be helpful in some circumstances, although individual needs vary based on heat exposure, activity level, how much a person has been sweating, and underlying health conditions.

What are the signs of dehydration?

Signs of dehydration can include dark urine, dizziness, dry mouth, fatigue, confusion and a rapid heartbeat. If symptoms are prolonged or severe, or if a person also is experiencing chest discomfort or shortness of breath, they should seek medical attention.

Is coffee off-limits for people with AFib?

One cup of coffee a day generally isn’t a concern. Even two cups may be acceptable, although for some patients I recommend switching extra servings to decaf or half-caf. It’s most important that people pay attention to their own bodies. If caffeine consistently triggers symptoms, cutting back is recommended. I’m far more concerned about the consumption of multiple energy drinks, because high doses of caffeine and other ingredients in these drinks can increase the risk of arrhythmias.

Is it safe for people with AFib to exercise in the summer?

I encourage regular exercise for my patients with AFib. If physical activity consistently triggers episodes, the underlying AFib should be evaluated and treated rather than simply avoiding exercise. That said, it’s best to avoid strenuous exercise during the hottest part of the day and to stay well-hydrated if outside in the heat. To combat overheating, seek air conditioning, drink plenty of water, take a cool shower or use cool towels.

What if a person thinks they may have AFib?

If a person has heart palpitations and isn’t sure what is causing them, capturing an episode can be key for diagnosis and treatment. This is where wearable devices, such as smartwatches, can play a role. If a device can record an ECG, or electrocardiogram, during an episode, a physician can review the tracing to determine whether it is consistent with AFib. Wearable devices have helped us identify more patients sooner, allowing us to begin treatment sooner. Preventing stroke is a major goal of AFib treatment. People who have been diagnosed with AFib should work with their healthcare team to determine whether further evaluation by a cardiac electrophysiologist is appropriate.

Read more from Cedars-Sinai Stories and Insights: Atrial Fibrillation—Know the Warning Signs

L-glutamine, an amino acid that occurs naturally in the body and plays an important role in digestion, has been studied as a potential way to ease side effects in other cancers. But this was the first trial to evaluate it as an anti-cancer therapy in human patients, said Jun Gong, MD, associate professor of Medicine, medical director of Colorectal Cancer at Cedars-Sinai Cancer and first author of the study.

“Current treatment for stage 4 pancreatic cancer is a cocktail of chemotherapy, with overall survival ranging from eight to 13 months,” Gong said. “We found that by adding L-glutamine to this treatment, we increased overall survival to as much as 22 months—and these positive results merit larger clinical trials of this combination.”

In this Phase I clinical trial, investigators studied 16 patients with advanced pancreatic cancer. All patients were treated with a standard chemotherapy combination of gemcitabine and nab-paclitaxel, along with clinical-grade L-glutamine supplements.

“We began the trial in the hope of improving gut health in these patients,” said Neil Bhowmick, PhD, Mark Goodson Chair in Oncology Research, professor of Medicine and Biomedical Sciences, research scientist at Cedars-Sinai Cancer, and senior author of the study. “Patients with pancreatic cancer do not absorb nutrients well, and often develop a condition called cachexia—a loss of weight and muscle that can be fatal. Glutamine is known to help the gut heal.”

Half of the patients in the study maintained their weight, and investigators found a correlation between the way the bacteria in the gut responded to the glutamine and patient outcomes, Gong said.

“At the time of our paper’s publication, the life expectancy of these patients taking glutamine and chemotherapy was more than double the average life expectancy associated with the historical standard of care,” Gong said. “The study did not compare the two options head-to-head, but our result is striking enough for us to advance to a larger randomized trial where patients are given glutamine or not.”

In the lab, investigators also found that cancer cells exposed to high-dose glutamine were particularly vulnerable to chemotherapy, a result in line with the reduction in tumor size seen in patients.

“It is really satisfying to see science from the bench translated so well into patient outcomes,” Bhowmick said.

The supplements used in the study are approved by the Food and Drug Administration for treatment of sickle cell disease, meaning they are federally regulated, Bhowmick and Gong said.

“The survival rate for advanced pancreatic cancer is poor,” said Robert Figlin, MD, interim director of Cedars-Sinai Cancer. “This trial points to a potential new option for optimizing first-line chemotherapy for patients while also opening up a number of new avenues for our physician-scientists to study.”

Additional Cedars-Sinai authors include Hayato Muranaka, So Yung Choi, Mourad Tighiouart, Aleksandr Stotland, Jennifer Van Eyk, Omer H.M. Elmadbouh, Mouad Edderkaoui, Sunao Tanaka, Hideki Furuya, Arsen Osipov, Jeremy Lorber, Sandrine Billet, Stephen J. Pandol, and Andrew Hendifar.

Other authors include Shrikant Bhute, Ezinne R. Aja, Jonathan P. Jacobs, Alexzandra Morris, Johanna ten Hoeve-Scott, and Thomas Graeber.

Funding: This project was funded by the 2019 Tower Cancer Research Foundation Experimental Therapeutics Endowed Fund/Cedars-Sinai Cancer 2019 Developmental Funds for Investigator-Initiated Trials (IITs; J.G.). This project was also supported in part by the NIH National Center for Advancing Translational Sciences (NCATS) UCLA CTSI (UL1 TR001881-01; M.T.) and NCI grants P01CA233452 (M.T., S.J.P., N.A.B.) and U01 grant CA232859-01 (M.T.).

Competing Interest Statement: H.M., N.A.B., J.G. and A.H. have a pending patent related to the work.

Cedars-Sinai Health Sciences University is advancing groundbreaking research and educating future leaders in medicine, biomedical sciences and allied health sciences. Learn more about the university.

During FY 2026, which ended June 30, more than 9,400 donors supported the academic medical center’s operations, programs and initiatives. Three out of every four of these donors received care at Cedars-Sinai prior to contributing.

“The extraordinary commitment of our donors is a wonderful validation of the dedication and expertise of Cedars-Sinai employees as well as the remarkable generosity of the people we are privileged to serve,” said Peter L. Slavin, MD, president and CEO of Cedars-Sinai and the David and Meredith Kaplan Presidential Chair.

Emma Geller is an example of a patient whose family showed gratitude with a donation. The 13-year-old is cancer-free after being treated for non-Hodgkin’s lymphoma at Cedars-Sinai Guerin Children’s. Despite financial strain caused by major damage to their home in the January 2025 Palisades Fire, the Gellers remain committed to their annual support of pediatric hematology/oncology research and pediatric nursing at Cedars-Sinai.

“Our daughter received such tremendous care from amazing doctors, and we wanted to know how we could give back,” said Jordan Geller, Emma’s father. “If there was a way to make other people’s lives a little better as they were going through something like this, we wanted to do it.”

Some of the most meaningful philanthropic investments in Cedars-Sinai are unrestricted gifts to The Fund for Cedars-Sinai.

One example of unrestricted support this past year was a $10 million gift from the Ashkenazy family, providing flexible resources that can be directed where they will have the greatest impact. This support enables Cedars-Sinai to respond to emerging needs, invest in strategic priorities and pursue promising opportunities, helping advance our mission both now and in the years ahead.

“Unrestricted gifts are the fuel powering vital community health initiatives and the highest level of patient care,” said Heather Renshaw Vučetin, vice president of Development for Cedars-Sinai. “Gifts of every size improve our community’s health, which is priceless.”

Other recent major gifts included but were not limited to:

• The Cedars-Sinai Cayton BRCA Center: A $30 million gift from the Cayton Goldrich Family Foundation to create a center for research, diagnosis and comprehensive treatment of illnesses linked to mutations in the BRCA1 and BRCA2 genes.
• The Cedars-Sinai Holoman Health Equity Center: A $13 million gift from Eric and Terri Holoman to establish a center that will shape the future of equitable healthcare at Cedars-Sinai.
• A generous bequest from the estate of Joanna Carson, demonstrating the enduring impact of planned giving. By including the organization in her estate plans, Carson created a legacy that will strengthen our mission for future generations.

“Philanthropic support is a powerful catalyst for healing,” said Arthur J. Ochoa, JD, senior vice president and chief advancement officer for Cedars-Sinai. “Whether expressed through volunteering or making a financial gift, the simple act of giving is fundamental to Cedars-Sinai’s vision to make a meaningful and lasting difference in the Los Angeles community and beyond.”

Read more from Cedars-Sinai Stories and Insights: Strengthening Children’s Health

The multi-institutional study offers one of the clearest pictures of what happens during the earliest stages of disease. The findings could help researchers develop new ways to detect and prevent heart disease before plaque builds up inside arteries.

“We analyzed proteins and gene activity in coronary artery tissue from young adults who died of trauma and had no known coronary artery disease, and we found that more than half already had preclinical atherosclerosis,” said study first author Sarah Parker, PhD, an associate professor of Cardiology and Biomedical Sciences and co-director of the Proteomics and Metabolomics Core at Cedars-Sinai Health Sciences University. “This suggests that changes in cellular metabolism and communication begin before the inflammation long considered a hallmark of the disease.”

Published in the European Heart Journal, the study findings point to previously unrecognized molecular pathways—and a potential “master regulator” called MLXIPL—that could become targets for therapies aimed at preventing plaque from developing.

The Cedars-Sinai Newsroom spoke with Parker about the findings and how proteomics—the study of proteins—is helping researchers rethink the earliest stages of heart disease.

Why are proteins so important in understanding heart disease?

Proteins are the molecules that make cells function. They tell us how the body’s cells are responding to risk factors like cholesterol, blood pressure or smoking. Two people can have identical cholesterol levels, yet only one develops plaque. Proteins may help explain why. They provide a much more direct picture of what's happening inside the artery wall and may reveal why some people are more vulnerable to heart disease than others.

What did this most recent study reveal about the earliest stages of atherosclerosis?

Previous studies had shown that the earliest artery lesions can appear in the first decade of life. What we haven’t understood is what causes those early changes to progress into dangerous plaques that lead to heart attacks. In studying coronary artery tissue before people ever developed symptoms, we were able to capture some of the earliest molecular changes that appear to set the disease in motion. One of the biggest surprises was that we saw changes in cellular metabolism and communication before we saw the classic inflammatory signals traditionally associated with atherosclerosis.

To be clear, inflammation remains a defining feature of advanced atherosclerosis. What our study suggests is that important molecular changes begin much earlier. If we want to prevent plaque from forming, we need to understand those earliest changes—not just what happens after inflammation has already taken hold.

Explain MLXIPL, the potential ‘master regulator’ you identified.

We performed a master regulator analysis to identify the genes that may be coordinating these early events. Some of the regulators we found were exactly what we expected. But one stood out. MLXIPL is a transcription factor gene involved in cellular metabolism. Previous genetic studies have linked it to coronary artery disease through its role in the liver. Our findings suggest it may also play an important role directly within the artery wall. When we altered MLXIPL activity in lab-grown human artery tissue, we saw the protein changes we predicted. That makes it an exciting candidate for future therapies that interrupt disease before plaque develops.

How could these findings change atherosclerosis prevention?

Today, we estimate cardiovascular risk using factors such as high cholesterol, diabetes, smoking, age and family history. By the time plaque is visible on imaging, disease often is well underway. We hope to identify protein biomarkers in the blood that reveal what’s happening inside the artery wall much earlier. One day, a simple blood test could identify people who would benefit from preventive treatment before symptoms develop.

That said, our findings do not change current prevention recommendations. Managing cholesterol, blood pressure, diabetes, smoking, exercise and diet remain essential.

This study relied on a decades-long collaboration. Why was that essential?

This is a collaboration more than 20 years in the making. The project was spearheaded by proteomics pioneer Jennifer Van Eyk. (Van Eyk, PhD, is director of the Advanced Clinical Biosystems Research Institute in the Smidt Heart Institute at Cedars-Sinai and co-director of the Proteomics and Metabolomics Core.)

Our collaborators included investigators from many other institutions across the country. What began as a small group has grown into an ecosystem of investigators, trainees and collaborators. This kind of large-scale molecular study simply isn’t possible without that level of long-term partnership and shared expertise.

Cedars-Sinai Health Sciences University is advancing groundbreaking research and educating future leaders in medicine, biomedical sciences and allied health sciences. Learn more about the university.

Brain cells that release dopamine—a messenger chemical that drives motor control— package it into tiny membrane-bound sacs called synaptic vesicles. And these vesicles differ from vesicles used by brain cells that release other messenger chemicals, a study led by Cedars-Sinai Health Sciences University investigators shows.

The study, published in Science Advances, could lead to better understanding of Parkinson’s disease, a movement disorder that causes dopamine-releasing brain cells to progressively die. The death of these cells leads to the movement problems that characterize the disease.

“Our research sheds light on the different ways brain cells release chemical messengers, which the cells use to communicate with each other,” said Katlin Silm, PhD, assistant professor of Biomedical Sciences and Neurology and senior author of the study. “We identified key differences between brain cells that release dopamine and those that release other brain chemicals.”

Synaptic vesicles help brain cells to communicate by fusing with the cell membrane and releasing their contents into the space between cells. In the brains of laboratory mice, investigators found that dopamine-containing synaptic vesicles carry a distinct set of proteins compared to those containing other messenger chemicals.

“Our findings show that a vesicle’s composition is critical to determining how brain messenger chemicals are released,” said Silm, also a research scientist in the Board of Governors Regenerative Medicine Institute. “The differences we identified help explain the unique properties of dopamine release and lay the groundwork to explore how this affects the long-term stability of dopamine-producing brain cells.”

Additional Cedars-Sinai authors include Hrach Asmerian, Alexia J. Diaz, Jacob Alberts, Barathan Gnanabharathi, Anna M. Sanetra, and Noah Carr.

Other authors include Hongfei Xu, Juan A. Oses-Prieto, Poulomi Das, Alma L. Burlingame, and Robert H. Edwards.

Funding: This work was supported by The Larry L. Hillblom Foundation grant 2022-A-004-SUP (KS), Brain and Behavior Research Foundation grant 29845 (KS), National Institutes of Health grant R01NS138465 (KS), National Institutes of Health grant R01NS103938 (RHE), National Institutes of Health grant R01NS129803 (RHE). Mass spectrometry was performed at the Mass Spectrometry Resource at UCSF, which is supported by the Dr. Miriam and Sheldon G. Adelson Medical Research Foundation (JAO-P & ALB).

New Method Could Boost Blood Tests’ Colon Cancer Monitoring Value

Blood tests could become a more powerful tool for monitoring colon cancer progression and treatment response, based on a study led by Cedars-Sinai Health Sciences University investigators. Their findings, published in Experimental Hematology & Oncology, used single-cell profiling to analyze circulating tumor cells and noncancerous cells in patients’ blood.

“Our method looks beyond the tumor to also understand the patient’s response to the cancer,” said Jun Gong, MD, medical director of Colorectal Cancer at Cedars-Sinai and an author of the study. “It could help guide more personalized treatment decisions based on tumor behavior and patient condition.”

Investigators analyzed blood samples from patients with advanced colorectal cancer, looking at 10 different cellular characteristics and using single-cell analysis to refine their findings.

The method reveals important changes, such as tumor cells taking action to evade the immune system or normal cells showing inflammation. These changes would be missed with existing tests, Gong said.

If these findings are validated in larger studies, Gong said, this method would complement existing tools for cancer monitoring, including imaging and standard laboratory tests.

Additional Cedars-Sinai authors include Francesca Aguirre, MD; Lisa Zhou, BS; Aaron Denmark, BS; Rocio Alvarez, MsC; and Daniel M. Kim, MD.

Other authors include Gabriela Felix, PhD; and Megan P. Hitchins, PhD.

Funding: This study was funded in part by NCI grant R01CA252042 (MH), Cedars-Sinai Cancer Developmental Fund (MH) and the ASCO Conquer Cancer Career Development Award (JG).

Disclosures: J.G. reports receiving consulting fees and honoraria from the following companies: EMD Serono, Exelixis, Natera, Eisai, Janssen, Pfizer, Bayer, Taiho, Agenus, Seagen, and Caper Labs. G.F., J.G. and M.H. have a provisional patent application (Application No.: 64/039,184) related to the work described in this manuscript.

Hydrogen Sulfide Gas Linked to More Severe IBS Damage

Investigators at Cedars-Sinai Health Sciences University have identified how excess hydrogen sulfide gas produced by certain gut microbes alters gene activity in the small intestine. Their findings, published in mSystems, offer new insight into conditions associated with irritable bowel syndrome (IBS), one of the most common gastrointestinal disorders.

Small intestinal bacterial overgrowth (SIBO), intestinal methanogen overgrowth (IMO) and intestinal sulfide overproduction (ISO) are conditions in which gas-producing microbes over-multiply in the small intestine. The disorders are often connected to IBS. 

"Our results show that ISO, IMO and SIBO are biologically distinct conditions that will require different treatment approaches," said Mark Pimentel, MD, executive director of the Medically Associated Science and Technology (MAST) Program at Cedars-Sinai and corresponding author of the study. "The genes altered in these conditions are linked to a variety of symptoms and understanding these mechanisms will help us develop better therapies for patients."

Investigators analyzed small bowel tissues samples from patients and laboratory animals. They found the most extensive changes in gene activity in samples from patients with ISO, and more limited changes in SIBO and IMO samples.

The genetic changes affected immune activity, fluid absorption, movement of nutrients through the gut, antioxidant defenses and cellular energy production. These findings may help explain why hydrogen sulfide overproduction has been associated with diarrhea, abdominal pain and other severe gastrointestinal symptoms in patients with diarrhea-predominant IBS.

Pimentel said larger studies integrating breath testing and microbiome profiling are needed to further validate these findings and identify how they might inform new therapies.

Other Cedars-Sinai authors include Juliana de Freitas Germano, Gabriela Leite, Maria Jesus Villanueva-Millan, Daniel Brimberry, Mohamad Rashid, Ava Hosseini, Dilara Flora, Said Bogatyrev, Walter Morales, Stacy Weitsman, Maritza Sanchez, Ignacio Rivera, Cristina Moreno Fajardo, Victoria Murray, Gonzalo Parodi, Margie Parra, Gillian M. Barlow, Ali Rezaie and Ruchi Mathur.

Other authors include Zhe Lyu.

Funding: This study was primarily supported by the Medically Associated Science and Technology (MAST) Program at Cedars-Sinai Medical Center, Los Angeles, CA, and funded in part through private donations to the MAST Program.

Disclosures: Drs. Pimentel, Mathur and Rezaie report equity in APQ Health and have received licensing or consulting fees related to diagnostic breath-testing technologies from Gemelli Biotech and Brio-Medical. The remaining authors declare no competing interests.

Cedars-Sinai Health Sciences University is advancing groundbreaking research and educating future leaders in medicine, biomedical sciences and allied health sciences. Learn more about the university.

The designation from the condition’s oldest patient organization is awarded to programs with the infrastructure and experience needed to provide high-quality care to people with pulmonary hypertension, a type of high blood pressure that occurs in arteries of the lungs.

Pulmonary hypertension can make it difficult for blood to circulate through the lungs, forcing the heart to work harder. In severe cases, the condition can lead to heart failure. People with pulmonary hypertension often need care from several specialists.

The Cedars-Sinai Pulmonary Hypertension Clinic includes six physicians and one nurse practitioner. The pulmonary hypertension program combines cardiology and pulmonology, which allows patients to access multidisciplinary care from experts in the disease. Providers care for more than 250 patients each year and address multiple aspects of the disease, including diagnosis, medication management, symptom control and disease progression.

“At Cedars-Sinai, pulmonary hypertension specialists collaborate with colleagues in rheumatology, congenital heart disease, critical care medicine, lung transplantation and other specialties to create treatment plans tailored to patients,” said Yuri Matusov, MD, assistant professor of Medicine at Cedars-Sinai. “We are proud to care for an extraordinarily diverse patient population, some of whom come from very far away for their care.”

The association noted several outstanding aspects of the Cedars-Sinai Pulmonary Hypertension Clinic including:

• A team that collaborates and provides timely evaluation and management of people who are hospitalized and continues to provide consistent care when they leave the hospital.
• Monthly conferences with specialists in the Southern California region that allow for the review of complex pulmonary hypertension cases, knowledge-sharing and regional care coordination.
• For people with advanced disease, access to top-notch heart, lung and thoracic transplant programs.
• A research program led by doctors investigating potential treatments.

“We are honored for our clinic to have received this designation, the highest recognition available to pulmonary hypertension programs in the United States,” said Dael Geft, MD, assistant professor of Cardiology in the Smidt Heart Institute at Cedars-Sinai. “Ultimately, the greatest reward is helping our patients live longer, healthier and more fulfilling lives.”

Read more on the Cedars-Sinai Newsroom: Unique Cell-Based Approach for Pulmonary Arterial Hypertension Shown to Be Safe

The protein restores the blood stem cell niche—the specialized environment that supports blood-forming stem cells—allowing the bone marrow to resume producing the blood cells the body needs.

Their preclinical study, published in Blood, could yield future treatments that help cancer patients recover faster after chemotherapy and radiation.

“The mechanisms that govern how the blood stem cell niche recovers after injury are not well understood,” said John Chute, MD, director of the Division of Hematology and Cellular Therapy at Cedars-Sinai and senior author of the study. “We identified a mechanism that stimulates niche recovery, which opens an exciting avenue to help patients replenish their entire blood system after chemotherapy or radiation.”

Chute compared the niche to the soil in a garden in which blood stem cells—which generate all of the body’s blood cells—blossom or grow. The niche is made up of several types of cells that tend to the blood stem cells, spurring them to divide and multiply so that they can replace blood cells that are damaged or lost.

“Chemotherapy and radiation therapy cause severe DNA damage to the niche cells,” Chute said. “The blood stem cells can’t regenerate because of this damage to their ‘soil,’ and this depletes the patient’s blood count for weeks.”

For patients, this means debilitating fatigue and increased risk of infection, bleeding and prolonged hospitalization.

Investigators found that a protein called R-spondin 2, which amplifies the signaling in cells that line blood vessels in the bone marrow, speeds up the recovery of the niche. 

When investigators treated laboratory mice that had been exposed to total body irradiation with R-spondin 2, the blood stem cell niche—specifically the cells lining the blood vessels in the niche—recovered more quickly than in untreated mice.

A key and surprising finding was that R-spondin 2 acted on the vascular niche cells, rather than the blood stem cells themselves.

Chute said that these findings may open the door to future research focused on the discovery and augmentation of mechanisms for niche repair. Targeting such mechanisms could accelerate the recovery of patients receiving chemotherapy or undergoing stem cell transplantation.

“Our outcomes for patients undergoing blood and marrow transplant are exceptional,” said Robert Figlin, MD, interim director of Cedars-Sinai Cancer. “This type of translational research can yield further improvements for those patients and all patients undergoing chemotherapy or radiotherapy.”

Additional Cedars-Sinai authors include Vanessa N. Montinelli, Samantha Grohe, Xue Ying Song, Jacqueline Turnlund, Hannah Hackbart, Joshua Sasine, Morgan Brady, Masahiro Muraoka, Rucha Kadam, Flavia D. Cavicchioli, Sage Kang, Ashley Dawson, Mimoli Uehara, Courtny Dizon, Theresa Krack, Peibin Yue, and Yuwei He.

The paper’s other author is Kurt D. Hankenson, University of Michigan.

Funding: This work was funded, in part, by NIAID awards U01 AI159622 (PI: John Chute), R21 AI193964 and NHLBI award R01 HL086998 (PI: John Chute).

Cedars-Sinai Health Sciences University is advancing groundbreaking research and educating future leaders in medicine, biomedical sciences and allied health sciences. Learn more about the university.

An average woman has about a 13% chance of developing breast cancer during her lifetime, according to the National Cancer Institute. A BRCA1 or BRCA2 gene mutation raises breast cancer risk to 30%-70%, and BRCA testing is recommended for women with personal or family history of certain cancers, a known BRCA mutation in the family, or Ashkenazi Jewish ancestry.

“While most women who undergo genetic testing do not test positive for a cancer-risk-increasing BRCA mutation, they have generally been referred for testing because of strong personal or family cancer history,” said Fahima Dossa, MD, PhD, surgical oncologist at Cedars-Sinai Cancer and lead author of the study. “Future cancer risk for these women has not been well studied, and our findings are the first to calculate that risk so that we can better guide all women who undergo BRCA testing.”

Looking at the health records of almost 16,000 women who underwent BRCA testing in Ontario, Canada, from 2007 to 2016, investigators found that women who tested negative for a BRCA gene mutation still had a 25% lifetime risk of developing breast cancer.

And lifetime risk for those with a variant of unknown significance, which means little is known about that particular variant, was 30%, according to the findings.

Each patient’s individual risk for breast cancer was substantially affected by their family history. Among women who tested positive for a BRCA mutation, breast cancer risk varied from roughly 56% to 86%, depending on the number of immediate family members who had breast or ovarian cancer, the study found.

“Based on these findings, a physician might recommend more frequent mammograms or breast MRI to a BRCA-positive patient in their 50s or 60s with no family history of breast cancer, but suggest preventive mastectomy as an option for a young BRCA patient with several cases of breast cancer in the family,” Dossa said.

Dossa said that the only women in the study with the same breast cancer risk as the general population were those who had family history of cancer and a known BRCA mutation in the family, and were tested for that specific mutation but did not have the mutation.

“This study is a reminder to patients about the importance of having discussions with their doctors about genetic test results,” Dossa said. “We finally have some data to help inform those conversations.”

In July, Cedars-Sinai opened the Cedars-Sinai Cayton BRCA Center to provide coordinated screening, guidance and treatment to patients with BRCA mutations.

“Our leading-edge research supports our efforts to care for and improve outcomes for these patients,” said Robert Figlin, MD, interim director of Cedars-Sinai Cancer. “Connecting science with cancer care is at the heart of what we do.”

Other study authors include Kelly Metcalfe, RN, PhD; Zharmaine Ante, MSc; Ning Liu, PhD; Jordan Lerner-Ellis, PhD; Andrea Eisen, MD; and Nancy N. Baxter, MD, PhD.

Funding: This study was supported by ICES, which is funded by an annual grant from the Ontario Ministry of Health (MOH) and the Ministry of Long-Term Care (MLTC). This study also received funding from the Canadian Cancer Society (grant #315358). This work was also supported by the Canadian Institutes of Health Research (CIHR) grant funding no #148470.

Cedars-Sinai Health Sciences University is advancing groundbreaking research and educating future leaders in medicine, biomedical sciences and allied health sciences. Learn more about the university.

Gilliam, 32, suffered sudden cardiac arrest, an electrical malfunction of the heart that causes it to abruptly stop beating. The odds were stacked against him: Sudden cardiac arrest kills about 90% of those who experience it outside of a hospital. Survival depended on a chain of people acting within minutes.

A fellow dancer immediately started CPR. Other dancers ran out of the dance studio in search of an automated external defibrillator (AED) and found one at a nearby dentist’s office. A speech pathologist who had just completed CPR recertification and happened to be nearby used the AED to revive Gilliam’s heartbeat.

Paramedics then rushed Gilliam to the Cedars-Sinai Emergency Department, where he had another cardiac arrest. Surgeons placed Gilliam on extracorporeal membrane oxygenation (ECMO), a form of advanced life support that temporarily took over the work of his heart, giving it time to recover—or, if necessary, bridging him to a transplant.

Cedars-Sinai experts say Gilliam’s case illustrates the importance of bystander CPR and quick medical response.

“The key to G’bari surviving sudden cardiac arrest was the fast-acting individuals who provided CPR, facilitated the use of an AED, and the Cedars-Sinai Emergency Department and cardiothoracic surgery teams who began ECMO within the hospital,” said Evan Kransdorf, MD, PhD, assistant professor of Cardiology in the Smidt Heart Institute and one member of Gilliam’s team of physicians and surgeons.

During cardiac arrest, blood stops circulating, explained Pedro Catarino, MD, a cardiothoracic surgeon in the Smidt Heart Institute at Cedars-Sinai.

“The cells of the body, particularly the brain, will die within a few minutes without circulation,” Catarino said. “Gilliam’s heart was in and out of a rhythm that doesn’t sustain circulation, so the surgery team put him on emergency life support.”

Gilliam’s heart had ceased working, so he was listed in the organ donation system. After 12 days on life support, Gilliam received the news every transplant candidate hopes for: A donor heart had become available.

“Heart transplantation offers a new chance at life for patients like Gilliam,” Catarino said. “Gilliam is an athlete and can look forward to going back to his career with a heart that has a long lifespan.”

A pathology report showed Gilliam had a severe form of hypertrophic cardiomyopathy, an inherited condition that causes the heart muscle to thicken so that the heart cannot contract and pump blood properly. The condition likely caused Gilliam’s sudden cardiac arrest, his medical experts say.

“Many people with hypertrophic cardiomyopathy don’t have symptoms, and athletes who are used to pushing themselves to be out of breath might not realize they have it,” Kransdorf said.

Geneticists in the Smidt Heart Institute tested samples of Gilliam’s heart and found that he had a genetic variant associated with hypertrophic cardiomyopathy. Experts encourage anyone with a family history to be screened for the condition, which affects about 1 in 500 people. Gilliam’s close family members are undergoing genetic testing.

Gilliam, whose credits include performing with Bad Bunny and on Jimmy Kimmel Live!, is now in physical therapy and preparing to return to dance.

“With dancing, it feels like I'm able to be my most authentic self and be the most vulnerable version of myself. It makes me feel alive,” he said.

Prior to his medical emergency, Gilliam’s schedule consisted of dance classes and gym training five days a week. He hopes to return to intense days and to continue teaching dance to elementary school students and choreographing dancers on TV and film sets. His mother and girlfriend are supporting him, as are many friends, family members and fellow dancers.

“What I learned from this experience is everyone should be trained in CPR because you never know what's going to happen,” Gilliam said. “Even more so, be a person of service. If you have the opportunity to help someone, do it.”

Read more from Cedars-Sinai Stories and Insights—Sudden Cardiac Arrest: Genetic Cause More Common in Younger People

A new study led by Karlstaedt and published in Circulation reports that a specific enzyme plays an important role in keeping the heart beating. The discovery could help scientists create drugs that mimic the enzyme’s role and help people with heart failure, a condition in which the heart becomes too weak to pump blood properly.  

Karlstaedt, assistant professor of Cardiology in the Smidt Heart Institute at Cedars-Sinai, has spent more than a decade studying heart metabolism—the chemical process that powers the heart. She spoke with the Cedars-Sinai Newsroom about her dedication to uncovering treatments for the millions diagnosed with heart failure every year.

How is the heart’s metabolism different from the metabolism of other parts of the body?

There are thousands of tiny molecules called metabolites—including amino acids, glucose and fatty acids—that act as an energy source to help cells function properly. The heart is the only organ that can use almost any metabolite.

The heart is also unique because it never stops beating. It's not like other muscles, which can rest. Fueling heart cells requires fine-tuned, organized chemical reactions. The system functions perfectly until something disrupts it, and metabolism is at its center. 

What was one of the major discoveries that led to your current work? 

My colleagues and I published a study in 2016 in which we discovered that the heart uses unusual fuel-processing routes to adapt to metabolites released by cancer cells. It’s like in a city where you have streets and traffic moves along those streets. If a construction site suddenly blocks a street, traffic finds another way around. The heart does the same thing.

We also found that in response to cancer-related metabolic stress, the heart suddenly started using an unusual enzyme called ATP-dependent citrate lyase, or ACL. This enzyme drives the process that creates fatty acids, something we didn’t think happened in heart cells. But when we blocked ACL, the heart could not pump well. That told us this enzyme might be much more important for the heart than previously thought.

Could you describe your recent discovery?

We found that when ACL slows down, heart function drops. To make this discovery, we studied heart tissue samples from people with healthy hearts and people with failing hearts. We also observed ACL in the hearts of laboratory mice. When ACL activity decreased, meaning it no longer efficiently produced fatty acids, the heart tried to adapt by taking up more sugar and rewiring parts of its metabolism. But those changes did not fully protect the heart. Instead, the heart had less available energy and did not pump as well.

To dig deeper, we used CardioNet, our computational model of heart metabolism. The model pinpointed another enzyme, IDH1, that compensates for the loss of ACL. When we reduced IDH1 in our model, the heart could pump better. We're now studying whether future heart failure therapies could target IDH1.

What do you hope to accomplish as this work progresses?

Heart failure can look similar from one patient to another, but the underlying metabolic changes may be different. We hope to use our computational model to predict which fuel pathways are disrupted in people with heart failure and which treatments can get the heart working better. We are not there yet, but this study is an important step toward understanding heart failure as a disease of both mechanics and metabolism.

Cedars-Sinai Health Sciences University is advancing groundbreaking research and educating future leaders in medicine, biomedical sciences and allied health sciences. Learn more about the university.

“The majority of people who have a sudden cardiac arrest outside of a hospital will die, so the best protection is being aware of risk,” said Kyndaron Reinier, PhD, MPH, associate director of Epidemiology in the Center for Cardiac Arrest Prevention in the Smidt Heart Institute at Cedars-Sinai and an author of both studies. 

Sudden cardiac arrest happens when a problem with the heart’s electrical system causes the heart to stop beating. It is different from a heart attack, which is caused by a lack of blood flow to the heart. More than 350,000 people experience sudden cardiac arrest outside of a hospital in the U.S. each year, and only about 10% survive. 

Experts know that people with low left ventricular ejection fraction, when the heart’s main pumping chamber is weak and pumps less than it should, are at higher risk for sudden cardiac arrest. But this marker has become less effective and other indicators are needed to capture more people at risk.

“More than two-thirds of people who have cardiac arrest don’t have low left ventricular ejection fraction, so using this marker alone misses too many people,” Reinier said. 

A study published in the journal Circulation: Arrhythmia and Electrophysiology reports that warning symptoms combined with clinical history could predict imminent sudden cardiac arrest. A second study, published in the Journal of the American Heart Association (JAHA), reports that having more than one cardiac event over time could signal rising risk. 

Reading Warning Symptoms

In the Circulation: Arrhythmia and Electrophysiology study, investigators used machine learning to identify combinations of symptoms and medical history that best predicted sudden cardiac arrest in the near future. 

The study included people enrolled in two separate, longstanding studies in Oregon and Ventura County, California, that were founded by Sumeet Chugh, MD, director of the Center for Cardiac Arrest Prevention in the Smidt Heart Institute. The investigators compared 364 people who called 911 when experiencing symptoms such as chest pain and survived sudden cardiac arrest, with 313 people who called 911 for similar symptoms but did not experience sudden cardiac arrest. 

The analysis found that people with sudden cardiac arrest were more likely to have a combination of shortness of breath and diagnosed coronary artery disease or heart failure than people who did not experience sudden cardiac arrest. Seizure-like symptoms without chest pain or shortness of breath were also more common in people who experienced sudden cardiac arrest.

The investigators also found that chest pain combined with coronary artery disease predicted imminent arrest in women, while chest pain combined with heart failure predicted it in men. 

Warning symptoms most often occurred at least 15 minutes prior to the sudden cardiac arrest, a time frame that would make it possible to call 911. In earlier research, the investigators found that 81% of people delayed their 911 call, reducing their chances of successful revival by ambulance paramedics. 

These findings could be used to create risk-predicting algorithms for use by urgent care and emergency medicine providers, the investigators said. “While more research is needed, such risk prediction algorithms have the potential to avoid 911 call delays following warning symptoms of sudden cardiac arrest,” said Chugh, vice dean and chief AI health research officer at Cedars-Sinai.

Tracking Risk Over Time

The JAHA study was carried out in the Observational Study of Cardiac Arrest Risk (O.S.C.A.R.) cohort at Cedars-Sinai, established by Chugh, that has been tracking the health of approximately 400,000 residents of Los Angeles County from 2017 onward. Of these, the investigators followed more than 6,700 people hospitalized at Cedars-Sinai for heart failure and more than 2,900 people hospitalized in the health system for acute coronary syndrome, when an artery blockage reduces blood flow to the heart. 

Investigators found that patients in both groups who experienced a recurrent cardiovascular event faced a higher risk of sudden cardiac arrest. 

Patients who had a second coronary artery blockage were more than three times as likely to experience sudden cardiac arrest as those without a recurrence. Patients who were hospitalized a second time for heart failure were nearly twice as likely to experience sudden cardiac arrest. Risk climbed with each additional heart failure hospitalization. The investigators compared the findings to what was found in participants of the Framingham Heart Study, which enrolled participants about 50 years earlier. The results were similar, however the heart failure result in that study did not reach statistical significance.

Reinier said that physicians should consider sudden cardiac arrest as being more likely when a patient is hospitalized for a heart issue a second time.

“This may mean running additional tests,” Reinier said. “It may mean educating the patient about what cardiac arrest is and the importance of having a family member who knows to call 911 and start CPR immediately if their loved one collapses.”

Moving Beyond Dead Ends

Chugh, senior author of both studies, said the combined findings point toward a more flexible approach to prediction.

“Near-term and long-term predictions are parallel approaches that can help us move past roadblocks we face in preventing death from this lethal heart event,” Chugh said.

Additional research, including studies in different populations, are needed to confirm whether the factors the investigators studied could be used in prediction tools, study authors said. 

Cedars-Sinai investigators continue to study predictors of sudden cardiac arrest, and their work includes using AI to study patterns in heart tests called electrocardiograms and looking for genetic causes. 

Additional Cedars-Sinai authors in the Circulation: Arrhythmia and Electrophysiologystudy include Harpriya Chugh, BS; Vishnu Kadiyala, MD; Arayik Sargsyan, MPH; Audrey Uy-Evanado, MD; Kotoka Nakamura, PhD; Elizabeth Heckard, MS; Marco Mathias, BS.

Other authors include Tristan Grogan, MS; David Elashoff, PhD; Angelo Salvucci, MD; and Jonathan Jui, MD, MPH.

Funding: Dr. Chugh was funded by the National Heart Lung and Blood Institute, National Institutes of Health.

Additional Cedars-Sinai authors in the Journal of the American Heart Association study include Marita Knudsen Pope, MD, PhD; Harpriya Chugh, BS, MSHS; Thien Tan Tri Tai Truyen, MD; Marco Mathias, BS; and Audrey Uy-Evanado, MD.

Other authors include Honghuang Lin, PhD; Dan Atar, MD, Nichole Bosson, MD, MPH, and Emelia J. Benjamin, MD, ScM

Funding: The Framingham Heart Study is funded by the National Heart, Lung, and Blood Institute, National Institutes of Health. Dr. Benjamin is partially funded by The National Heart, Lung, and Blood Institute, National Institutes of Health.

Cedars-Sinai Health Sciences University is advancing groundbreaking research and educating future leaders in medicine, biomedical sciences and allied health sciences. Learn more about the university.

The preclinical study was published in Cell Reports Medicine. 

“Our study is the first to show how metabolites produced by select bacteria can induce changes in the body’s immune response when the body is fighting cancer,” said Ze’ev Ronai, PhD, director of the Translational Research Institute at Cedars-Sinai, professor of Surgery and senior author of the study. “Previous research established that gut bacteria affect the immune system and can help fight cancer. Our new findings are an important step forward because they give us a specific metabolite that can be used for future therapies.” 

The investigators focused on B. rodentium in the guts of mice and a related bacteria species, B. uniformis, in the guts of humans. When these bacteria break down the amino acid tryptophan, they produce different forms of metabolites called indoles. 

In laboratory mice, investigators found that treatment with B. rodentium restricted the growth of melanoma and colon, breast and pancreatic cancers, and that treatment with indole on its own restricted the growth of melanoma.

“Indole was more effective against these tumors than other metabolites produced by tryptophan breakdown, which are used in immunotherapies,” said Ximena Diaz Olea, a research scientist in the Ronai Lab and first author of the study. 

The investigators also looked at data from human patients who were responding well to immunotherapy for melanoma. In these patients, investigators found increased levels of the enzymes used to produce indole, suggesting higher levels of indoles were contributing to the patients’ good outcomes. 

“We are now evaluating whether increasing the levels of indoles in the gut would be sufficient to inhibit cancer,” Ronai said. “We hope to turn these findings into a therapy that will benefit patients.”

Investigators say this might be possible by giving patients capsules containing B. uniformis, then following up with nutrients to increase the bacteria’s reproduction and indole levels in the gut.

While this study focused on B. uniformis and B. rodentium, as many as 20 different bacteria species produce the enzyme that creates indole, opening further avenues for exploration, Ronai said. 

“These findings provide the foundation for modes of treatment that could complement or replace existing ones,” said Robert Figlin, MD, interim director of Cedars-Sinai Cancer. “This type of translational science paves the way toward new options for patients.” 

If investigators are successful at translating their findings into an anticancer therapy, Ronai said that it would likely be useful against many cancer types, as the immune cells bolstered by indole are effective against many cancers.

Additional Cedars-Sinai authors include Ximena Diaz Olea, Aagam Shah, Hyungsoo Kim, Ashok Kumar Sharma, Anthony Martin, Mark B. Faries, Omid Hamid, Suzanne Devkota, and Simon Knott.

Other authors include Kristin Beede, Gabriel Pereira, David Scott, Christopher Petucci, Eric Martens, Dmitri Rodionov, Miguel P. Martinez, Tongwu Zhang, Andrei Osterman, Emile E. Voest, Nadim J. Ajami, Jennifer Wargo, and Amanda E. Ramer-Tait.

Funding: This work was supported by the Cedars-Sinai shared resources in genomics, vivarium and microbiome studies; NCI grant R35CA197465 (to ZAR); the Hervey Family / San Diego Foundation (to ZAR); grant R21CA249822 (to ART and HK); and the Buffett Cancer Center funds (to ART) via NCI grant CA036727.

Cedars-Sinai Health Sciences University is advancing groundbreaking research and educating future leaders in medicine, biomedical sciences and allied health sciences. Learn more about the university.

Cedars-Sinai Study Links Hypertension to Socioeconomic Level

People living in under-resourced neighborhoods are more likely to develop high blood pressure—also known as hypertension—than those in wealthier areas, according to new research from Cedars-Sinai Health Sciences University. The study was published in the American Journal of Hypertension.

“The increased risk for people in the least healthy neighborhoods was similar to being a full decade older than their counterparts in the healthiest neighborhoods,” said Joseph Ebinger, MD, MS, associate professor of Cardiology and director of the Coronary Intensive Care Unit in the Smidt Heart Institute at Cedars-Sinai and senior author of the study. “Although such disparities in hypertension prevalence are known to occur, our study is notable because it demonstrates the persistence of these differences over time.”

Investigators tracked the blood pressure of more than 94,000 Cedars-Sinai patients between 2018 and 2023. They found that, over time, patients in neighborhoods in the lowest 25% of rankings on a scale that assesses education, job opportunities and other social conditions were 7% more likely to develop high blood pressure than patients in the top 75% of neighborhoods.

“Many people do not know they have hypertension and are not being treated for it,” Ebinger said. "Our findings suggest clinicians may consider targeting interventions in the context of socioeconomic data to help prevent at-risk patients from developing the condition, which increases their risk for heart disease, kidney disease and stroke."

Additional Cedars-Sinai authors include Jonathan N. Le, MD; Tzu Yu Huang, MPH; Patrick G. Botting, MSHS; Ellie Albertson, MPH, PhD; Natalie A. Bello, MD, MPH; Christina Harris, MD; Alan Kwan, MD; and Susan Cheng, MD, MPH. 

Other authors include Brian Claggett, PhD.

Funding: This study was supported by grant funding from the NIH/NHLBI (K23HL 153888-03) and by the Smidt Discovery Fund of the Smidt Heart Institute.

Study Links Angina Severity to Composition of Heart Plaque 

About half of women who experience angina, chest pain presumed to be from obstructed blood flow to the heart, don’t have significant coronary artery blockage. And yet, these women have elevated risk for heart attacks and strokes. New research from Cedars-Sinai Health Sciences University, published in Communications Medicine, helps explain why.

Investigators found that buildup in the coronary arteries of women with severe angina was more likely to consist of soft plaque. Soft plaque, also known as noncalcified plaque, is more prone to rupture and trigger dangerous blood clots than its more stable counterpart, known as calcified or hard plaque. 

The findings were based on artificial intelligence analysis of more than 100 CT coronary angiograms (noninvasive heart scans) performed on women with angina and coronary artery disease.

“Our findings expand our understanding of why angina occurs in women without significant artery blockages,” said Damini Dey, PhD, professor of Biomedical Sciences at Cedars-Sinai and corresponding author of the study. “The findings also suggest the need to consider treating these women with medications to prevent the buildup of plaques and reduce the risk of heart attacks and other cardiac events.”

Other Cedars-Sinai authors include Rafal Wolny, Guadalupe Flores Tomasino, Kajetan Grodecki, Joel Lenell, Caroline Park, Rebekah Park, Jacek Kwiecinski, Daniel S. Berman, Piotr J. Slomka, Janet Wei, Martha Gulati and C. Noel Bairey Merz.

Other authors include Osama Dasa, Vinicius Calsavara, Matthew J. Budoff, Eileen Handberg, Carl J. Pepine, Leslee J. Shaw and Balaji Tamarappoo.

Acknowledgements: This study was primarily supported by grants from the NHLBI R01HL151266 and 1R01HL148787. It was also supported by CDMRP-DoD W81XWH-17-2-0030 and McJunkin Family Foundation through funds distributed by the University of Florida, Department of Medicine, Clinical Research Consortium CDRN-1501-26692, the Edythe L. Broad and the Constance Austin Women’s Heart Research Fellowships, Cedars-Sinai Medical Center, Los Angeles, CA, the Barbra Streisand Women’s Cardiovascular Research and Education Program, Cedars-Sinai Medical Center, Los Angeles, the Linda Joy Pollin Women’s Heart Health Program, the Erika Glazer Women’s Heart Health Project, Cedars-Sinai Medical Center, Los Angeles, CA; and the VA Women’s Health Practice-Based Research Network VA HSR&D SDR 10-012. R.W. is supported by a Polish National Science Centre (grant number 2021/43/D/NZ5/02434) and Medical Research Agency (grant number KPOD.07.07-IW.07-0150/24).

Competing interests: Drs. Berman, Slomka, and Dey have received software royalties from Cedars-Sinai Medical Center and report equity in APQ Health.

How the Brain Influences Aging Throughout the Body

Cedars-Sinai Health Sciences University investigators are helping clarify the brain’s role in how the body ages. Their study, published in Nature Communications, identified a group of brain cells that become overactive with age and may impair the body’s ability to maintain consistent temperature, stay properly hydrated and efficiently convert food into energy. 

“These age-related problems make the body more vulnerable to illness and often rob people of their independence,” said Celine Riera, PhD, associate professor of Biomedical Sciences and Neurology, research scientist in the Board of Governors Regenerative Medicine Institute at Cedars-Sinai, and senior author of the study. “We found that a group of brain cells that produce a hormone called vasopressin become overactive with age, contributing to these problems.”

These brain cells are in the hypothalamus, at the base of the brain. In healthy amounts, the vasopressin they produce helps blood vessels constrict. It also helps the kidneys control the amount of water and salt in the body, which helps control blood pressure and urine output. 

When investigators artificially activated these brain cells in young laboratory mice, the cells produced more vasopressin and the mice developed changes similar to those seen in aging mice. Conversely, when investigators reduced the activity of these brain cells in aging mice, the mice were better able to maintain body temperature, hydration and metabolism, Riera said.

The findings provide scientists with new context for understanding how the brain contributes to systemic aging. Future studies may explore whether therapies targeting these brain cells can reduce age-related health problems and improve quality of life in aging people, Riera said.

Additional Cedars-Sinai authors include Nancy Morones, Predrag Jovanovic, Anna Sanetra, Kaitlyn Jang, Nareg Keshishian, Zhihan Clay Cui, Edward Novinbakht, Joshua J. Breunig, Anders Berg, Tamar Pirtskhalava, Selim Chaib, S Ananth Karumanchi, Tamar Tchkonia, Katlin Silm, and James L. Kirkland.

Funding: This work was supported by the Larry L Hillblom Foundation startup grant (C.E.R.), the Cedars-Sinai Pilot Award from the Center on Aging and Diabetes (C.E.R.), the CIRM Scholar fund EDUC-12751 (N.M.), the National Institute of Aging grant RF1AG091203 (C.E.R.) and R37AG013925 (J.L.K., T.T.).

Possible Biomarker Linked to Aggressive Thyroid Cancer

Cedars-Sinai Health Sciences University investigators have found a possible way to identify which patients are at greatest risk of thyroid cancer recurrence and might benefit from more aggressive treatment. Their findings were published in Science Advances.

“The incidence of thyroid cancer has tripled over the past three decades and it is now the most common cancer in adolescents and young adults,” said Anthony T. Nguyen, MD, PhD, assistant professor of Radiation Oncology and Biomedical Sciences and first author of the study. “The biomarker we identified, if further validated, could help us identify patients likely to have more aggressive disease so that we can intensify their treatment.” 

In five patients with locally advanced thyroid cancer, investigators used single-cell RNA sequencing to analyze gene expression patterns in individual cells of the tumor microenvironment, comparing primary thyroid tumors and matched lymph nodes to which cancer had spread. Their findings were confirmed in a separate group of 21 patients with thyroid cancer.

Among multiple differences between primary tumor and lymph node, investigators found that an increase in IL7 receptor protein expression on the surface of immune cells in the lymph nodes was linked to improved patient outcomes.

“Our study is one of the first to use single-cell RNA sequencing to identify a lymph node-specific biomarker for aggressive thyroid cancer,” said Allen Ho, MD, professor of Surgery and co-corresponding author of the study. “Low levels of IL7 receptor in the lymph node can potentially be used to identify patients with more aggressive disease who are candidates for treatment intensification.”

The other corresponding author is Stephen Shiao, MD, PhD, professor of Radiation Oncology and Biomedical Sciences and co-leader of the Cancer Therapeutics Program.

“This study is an example of the promise of single-cell RNA sequencing to assess the status of tumors for more targeted treatment,” said Robert Figlin, MD, interim director of Cedars-Sinai Cancer. 

Additional Cedars-Sinai authors include Jolene Viramontes, Isaiah Vazquez, Catriona McWilliam, Vaishnavi Devarakonda, Regina Henson, Wendy L. Sacks, Jon Mallen-St Clair, Yufei Chen, Evan Walgama, Kevin S. Scher, Justin Moyers, Julie K. Jang, Zachary S. Zumsteg, and Wonwoo Shon.

Howard M. Sandler is also an author of the study.

Funding: This work was supported by: National Institutes of Health grant K08CA191139 (SLS), Conquer Cancer Young Investigator Award (ATN), American Society for Radiation Oncology Junior Faculty Award (SLS), Cedars-Sinai Precision Health Grant (ASH).

New Expert Consensus Aims to Improve Diagnostics in Emergency Care

Cedars-Sinai Health Sciences University investigators convened a panel of medical experts to develop new definitions to improve diagnostic quality and safety in emergency departments. The definitions—diagnostic excellence and missed diagnostic opportunity—address a longstanding gap in the field, as they recognize the role uncertainty plays in emergency care. Their findings are published in Annals of Emergency Medicine. 

“Our new definitions can be used to guide investigations about the diagnostic process in emergency departments to identify opportunities for improvement,” said study first author Carl Berdahl, MD, MS, associate professor of Medicine and Emergency Medicine at Cedars-Sinai. “Future work should explore the integration of these definitions into diagnostic research and quality and safety programs, and evaluate the impact on patients’ health outcomes.”

A 2022 report from the Agency for Healthcare Research and Quality suggested about 1 in 18 patients visiting emergency departments each year receive a misdiagnosis that causes preventable harm or worsens their outcome. This report sparked controversy about what the emergency department’s role should be in assigning diagnoses.

The panel of 10 experts from emergency medicine and related specialties reviewed scientific evidence to arrive at the new definitions. It defined “diagnostic excellence” as using evidence-based practices to arrive at an accurate and timely explanation of a patient’s condition based on the information available at the time; communicating that diagnosis to patients and families; and providing equitable, patient-centered care. It defined a “missed diagnostic opportunity” as a measurable departure from evidence-based practice that may contribute to a delayed or inaccurate diagnosis, or a failure in communicating diagnostic information to patients and families.

Additional Cedars-Sinai authors include Sam S. Torbati, MD; Maxim P. Ptacek, BS; Nabeel Qureshi, PhD; and Teryl K. Nuckols, MD, MSHS.

Additional authors include Gordon D. Schiff, MD; Arjun K. Venkatesh, MD, MBA; Edward G. Seferian, MD, MS; and Johan Carrascoza-Bolanos, BS.

Members of the Multidisciplinary ED Diagnostic Excellence Panel include Adebisi Alli, DO, MS; Marie L. Crandall, MD, MPH; Anuj K. Dalal, MD; Kelly T. Gleason, PhD, BSN; Sachin Gupta, PhD, MBA; Aaryn K. Hammond, MD; Victoria Nash, MS; Michelle D. Lall, MD, MHS, Robert Sherwin, MD; Scott D. Steenburg, MD, MS.

Funding: This work was supported by the Emergency Medicine Foundation’s Diagnostic Excellence in Emergency Medicine Grant. Dr. Berdahl was also supported by K08HS029534 and the National Academy of Medicine Scholars in Diagnostic Excellence Program.

Preclinical Study: Novel CAR T-Cell Therapy Controls Bladder Cancer

Investigators at Cedars-Sinai Health Sciences University have discovered that delivering a specialized CAR T-cell therapy directly into the bladder could control bladder cancer and reduce the need for bladder-removal surgery. The preclinical study, published in the Journal of Experimental Medicine, identifies a strategy that, after further testing in humans, could improve management of organ-confined tumors.

“Current bladder cancer therapies are limited by drug shortages, severe side effects and high recurrence rates, often forcing patients to undergo life-changing bladder-removal surgery,” said Parwiz Abrahimi, MD, PhD, urologic oncologist in the Department of Urology at Cedars-Sinai and first author of the study. “This new strategy has the potential to dramatically reduce the necessity for bladder removal, preserving the patient’s quality of life while maintaining control of their cancer.”

In laboratory mice, investigators found this localized approach safely confined the treatment to the bladder and prevented the engineered cells from escaping into the bloodstream. The findings support the practice of delivering cellular therapies directly via a catheter to treat organ-confined bladder cancers.

Additional authors include Jonathan F. Khan, Alyssa Duren-Lubanski, Winson Cai, Yacine Marouf, Nan Chen, Daniel Hirschhorn, Renata Mammone, Ileana C. Miranda, Jacob E. Tallman, Alejandra Vela-Moreno, Mohamad Hamieh, Bishoy M. Faltas, Thomas M. Carroll, Micaela L. Everitt, Hari K.K. Subramanian, Hikmat A. Al-Ahmadie, Olivier Elemento, Benjamin D. Hopkins, Douglas S. Scherr, Renier J. Brentjens, Jedd D. Wolchok and Taha Merghoub.

Cedars-Sinai Scientists Identify New Driver of Inflammation 

Investigators at Cedars-Sinai Health Sciences University have identified a previously unrecognized driver of harmful inflammation. The findings, published in Nature Communications, center around TRIM21, a protein also linked to autoimmune disease.

“Our findings suggest TRIM21 may be one reason some autoimmune and autoinflammatory diseases share similar features,” said Jessica Carriere, PhD, an assistant professor of Pathology and Laboratory Medicine at Cedars-Sinai and co-corresponding author of the study. “By targeting TRIM21, we may eventually be able to develop new treatments for a range of inflammatory diseases.”

Researchers discovered that TRIM21 helps build the inflammasome, an alarm-like structure inside immune cells that triggers inflammation. While this alarm helps protect the body from infection, it also can become overactive and trigger excessive inflammation that damages healthy tissue and contributes to disease. 

The study, which looked at laboratory mice and human patient samples, showed that TRIM21 not only helps activate this inflammatory response but also enables inflammatory signals to spread from dying immune cells to nearby cells, potentially creating a chain reaction that drives inflammation throughout the body.

Additional Cedars-Sinai authors include Sana Ismaeel, Elisabeth Jäger, Vinicius Dantas Martins, Kaiden A. Sims, Huyen Nguyen, Justin Ruiz, Hemisha Khatri, Savita Devi, Andrea Dorfleutner and Christian Stehlik. 

Additional authors include Chawon Yun, Sonal Khare, Lan H. Chu, Lucia de Almeida, Janset Onyuru, Jae Jin Chae, Daniel L. Kastner, Lori Broderick and Hal M. Hoffman.

Funding: This work was supported by the National Institutes of Health (AI099009 to C.S., AI134030, AI140702, DK143393, CA301129 and AI165797 to C.S. and A.D.), the American Heart Association (834502 and 26CDA1588880 to J.C., 25POST1374216 to S.I., 26POST1558214 to V.D.M., 15PRE25700116 to L.H.C. and 18CDA34110296 to L.d.A.), and the American Cancer Society (PF-23-1149877-01-IBCD to E.J.).

Cedars-Sinai Health Sciences University is advancing groundbreaking research and educating future leaders in medicine, biomedical sciences and allied health sciences. Learn more about the university.

Shehata is a cardiac electrophysiologist, a doctor who specializes in diagnosing and treating problems with the heart’s electrical system. He has experience with a broad spectrum of heart rhythm disorders and also cares for people with heart failure and survivors of cardiac arrest.

“Over the past two decades, Dr. Shehata has emerged as a nationally recognized cardiac electrophysiologist and academic leader,” said Susan Cheng, MD, MMSc, MPH, chair of the Department of Cardiology in the Smidt Heart Institute. “His leadership will mean continued progress in this important field.”

As a researcher, Shehata has led groundbreaking clinical trials for new types of pacemakers and other technologies for treating heart rhythm disorders. He also studies ways that AI can be used to personalize care.

Shehata’s most recent research includes a trial of a new treatment for atrial fibrillation, which occurs when the upper chambers of the heart beat out of sync with the lower chambers of the heart. The treatment, pulsed field ablation, targets heart cells involved in an abnormal heart rhythm. The U.S. Food and Drug Administration approved several pulsed field ablation systems, including one studied by Shehata and other researchers, in 2024.

Shehata and colleagues have also studied leadless pacemakers, miniature devices that attach to the heart muscle and that, unlike traditional pacemakers, don’t require a battery and wires.

As division director, Shehata will oversee a program that provides research-backed care and trains new heart rhythm specialists. The program offers a two-year fellowship to medical school graduates seeking advanced knowledge and skills in electrophysiology.

“Through his leadership of the Interventional Electrophysiology Laboratory and the Clinical Cardiac Electrophysiology Fellowship Program, Dr. Shehata has expanded access to advanced therapies and enhanced the training of future electrophysiologists,” said Eduardo Marbán, MD, PhD, executive director of the Smidt Heart Institute and the Mark S. Siegel Family Foundation Distinguished Professor.

Shehata earned his medical degree from the University of California, San Diego, School of Medicine. He completed internal medicine residency training at UCLA and his cardiology fellowship training at Cedars-Sinai, where he was chief fellow. He also completed advanced fellowship training in cardiac electrophysiology at Cedars-Sinai. He served as faculty at UCLA before being recruited to join the cardiology faculty at Cedars-Sinai, where he is a professor of Cardiology.

U.S. News & World Report rates the Smidt Heart Institute a top 10 cardiovascular center in the U.S. and #1 in California.

Read more from Cedars-Sinai Stories and Insights: New AFib Treatment Helps Dad Regain His Heart Rhythm

The model addresses a longstanding challenge in hospital care. Low blood sugar, also called hypoglycemia, is a common and potentially life-threatening complication among hospitalized patients, including those receiving diabetes treatment, those who are fasting before procedures or those in critical care. However, there are no widely used tools for predicting which hospitalized patients may develop hypoglycemia.

“Today, most hospital care for hypoglycemia is reactive, and we respond after a patient’s blood sugar drops,” said Roma Gianchandani, MD, senior author of the study and vice chair of Quality and Innovation in the Department of Medicine and program director for Diabetes.  

The AI model developed by Cedars-Sinai investigators analyzes patterns in medications, lab results, meals and other data from patients’ electronic health records. It collects the information in four-hour intervals over a five-day period and uses it to predict whether a patient will develop hypoglycemia within the next 24 hours.

Researchers developed and tested the model using data from more than 143,000 adult hospital admissions across three Cedars-Sinai Health System hospitals between 2014 and 2025. Investigators also tested the tool using prospective hospital data to confirm their initial findings.

“The AI model is designed to alert patient care teams before a patient experiences low blood sugar and identify the key factors driving that risk,” said Amanda Momenzadeh, PharmD, lead author of the study and a project scientist in the Meyer Research Lab at Cedars-Sinai. “By offering actionable insights to care teams, it also aims to support hospital diabetes management programs.”

Researchers estimate the tool could help prevent about three to four cases of low blood sugar at a large hospital each day. Extrapolating across all hospital beds worldwide, the impact could be substantial.

“What’s exciting is that this isn’t just a theoretical model, but instead, it is built and validated to work prospectively in real time using data hospitals already collect,” said senior author of the study Jesse Meyer, PhD, assistant professor in the Department of Computational Biomedicine at Cedars-Sinai. “By identifying patients at risk earlier, we have an opportunity to reduce preventable complications and improve patient safety.”

If widely adopted, the model could lead to more proactive, data-driven care for hospitalized patients with diabetes and other conditions that affect blood sugar.

Additional Cedars-Sinai authors: Caleb Cranney, Dennis Chen, and Elizabeth Nguyen.

Funding: NIGMS R35GM142502, NIH National Center for Advancing Translational Science (NCATS), and UCLA CTSI Grant Number UL1TR001881

Disclosure: Jesse Meyer, Amanda Momenzadeh, and Caleb Cranney are listed as inventors on a patent application related to this AI tool.

Cedars-Sinai Health Sciences University is advancing groundbreaking research and educating future leaders in medicine, biomedical sciences and allied health sciences. Learn more about the university.

Breast tumors are currently classified into basic subtypes such as HER2-positive and triple-negative. Based on a tumor’s subtype, doctors can prescribe chemotherapy, immunotherapy or other treatments to shrink the tumor before a patient undergoes surgery to remove it. This can allow some patients to have a lumpectomy rather than a full mastectomy.

Presurgical treatment, also called neoadjuvant treatment, can also help kill cancer cells that have spread beyond the breast, which can help prevent cancer from returning.

“The issue is that a single breast tumor can include many cancer subtypes, but current tests classify the whole tumor as one,” said Eytan Ruppin, MD, PhD, deputy director of the Translational Research Institute at Cedars-Sinai and co-corresponding author of the study. “With BRIDGE, we use gene activity to measure the various subtypes within a tumor and better pair patients with the most effective presurgical treatment.”

Together with the composition of the tumor, BRIDGE provides a score that tells clinicians how likely a patient is to respond to a given presurgical treatment. The tool analyzes the same tumor biopsy samples physicians routinely take when a patient is diagnosed.

“We addressed the most common presurgical treatments given in the major breast cancer subtypes,” said Thomas Cantore, PhD, a postdoctoral scientist in the Ruppin lab and co-corresponding author of the study. “Applying BRIDGE to data from hundreds of patient samples whose cancer type and treatment response were known, we found that it accurately predicts which patient may or may not respond to which therapy.”

Building on the work of others on Ruppin’s team, the investigators next took BRIDGE a step further.

“Our second step was to apply AI tools to BRIDGE to create BRIDGE-Slide,” said Nishanth Ulhas Nair, PhD, a research scientist in the the Jim and Eleanor Randall Department of Surgery and co-corresponding author of the study. “Rather than requiring costly genomic sequencing of the tumor, BRIDGE-Slide can infer the makeup of a tumor from an image of the biopsy slide. This saves time, and thousands of dollars, and could help democratize precision oncology, making personalized breast cancer treatment accessible to all.”

The next step for investigators is to further test BRIDGE and BRIDGE-Slide in clinical trials, Cantore and Nair said.

“These biopsy slides are a gold mine of information,” Cantore said, “and we are focused on leveraging them.”

Additional Cedars-Sinai authors include S.R. Dhruba, E. Campagnolo, J. Levy, K. Yao, I. Liao, and Y. Yuan.

Other authors include D-T. Hoang, L.R. Pal, A. Stemmer, T-G. Chang, E. Shulman, J.S. Lee, S.M. Stemmer, S-J. Sammut, S. Lipkowitz, P.S. Rajagopal, M. Filipits, and C. Caldas.

Funding: This research was supported in part by the Intramural Research Program of the National Institutes of Health (NIH), National Cancer Institute (NCI). The contributions of the NIH author(s) are considered Works of the United States Government. The findings and conclusions presented in this paper are those of the author(s) and do not necessarily reflect the views of the NIH or the U.S. Department of Health and Human Services. This research is partially supported by a grant of the Korea-US Collaborative Research Fund (KUCRF), funded by Ministry of Science and ICT and Ministry of Health & Welfare, Republic of Korea (grant number: RS-2024-00468417). This work used the computational resources of the NIH HPC Biowulf cluster (http://hpc.nih.gov). The results shown here are in part based upon data generated by the TCGA Research Network: https://www.cancer.gov/tcga.

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His labored breathing and exhaustion prompted him to see his physician, who ordered a battery of tests. Aster’s diagnosis: A rare cancer called a neuroendocrine tumor was causing a condition called carcinoid heart disease, and causing his heart to fail.

With treatment at the Cedars-Sinai Neuroendocrine Tumor Multidisciplinary Clinic, Aster is now back on the trail, his bike, his board and the court.

“I went from wondering how long I have to live to understanding that this can be managed,” Aster said. “I feel better than I have felt in years.”

Aster’s symptoms came on slowly over several months: crushing fatigue, bloating, loss of appetite and swelling in his legs and feet. Blood tests ordered by his primary doctor were normal, but a CT scan showed tumors in his liver, which were eventually diagnosed as stage 4 neuroendocrine cancer.

“We received the diagnosis the day we dropped the youngest of our four kids off at college,” Orr said. “We had other plans, so we just had to reset.”

Unable to sleep the night they got the news, Orr—who Aster said was his caregiver and support throughout this difficult time and credits with helping save his life—spent hours online. She clicked her way to the Neuroendocrine Tumor Research Foundation. The organization, a resource for research funding, patient education and support, directed the couple to  the Neuroendocrine Cancer Foundation, which referred them to Cedars-Sinai and its multidisciplinary clinic.

“We were concerned about Ken’s neuroendocrine tumors, which had spread to his liver and were making it difficult for his stomach to work normally,” said Andrew Hendifar, MD, who leads the clinic and is a professor of Medicine at Cedars-Sinai. “But we knew from experience that his heart failure would have to be treated first. We didn’t have a minute to lose.”

Neuroendocrine tumors begin in neuroendocrine cells, which connect the nervous system with the hormone-producing endocrine system. They can occur anywhere in the body.

Aster’s began in his small bowel and produced a hormone called serotonin, which thickened two of his heart valves and caused them to leak. The condition is called carcinoid heart disease.

Prashanth Venkatesh, MD, assistant professor of Cardiology in the Smidt Heart Institute at Cedars-Sinai, is the cardiologist on the neuroendocrine team.

“The pulmonary valve, which sends blood from the heart to the lungs, is notoriously difficult to evaluate with standard imaging techniques because of its location in the chest and the relative rarity of pulmonary valve disease in adults,” Venkatesh said. “Significant pulmonary valve involvement in carcinoid heart disease is hence very easily missed.”

Venkatesh, a congenital heart specialist, often employs more extensive imaging techniques for patients born with structural heart defects. Aster’s results showed there was a leak in his pulmonary valve as well as a leak in his tricuspid valve. Both valves needed to be replaced.

“When there is a leaky valve, which we call regurgitation, some of the blood in the heart goes in the wrong direction,” said Raj Makkar, MD, vice president of Cardiovascular Innovation and Intervention at Cedars-Sinai and the Karsh Distinguished Chair in Interventional Cardiology in the Smidt Heart Institute. “With leaky pulmonary and tricuspid valves, the blood that is supposed to go into the lungs can leak back toward the upper chamber of the heart.”

Aster’s pulmonary valve was replaced via a minimally invasive procedure in which a catheter was threaded up through an artery in the groin to maneuver the valve into its proper place. Four weeks later, Makkar replaced Aster’s tricuspid valve using a similar procedure. 

“Patients with carcinoid heart disease are going through a lot because of the neuroendocrine tumor, and traditional valve replacement surgery puts them at higher risk for complications,” Makkar said. “We pioneered testing of transcatheter tricuspid valve replacement around five years ago, and this was the option we chose for Mr. Aster.”

To address the neuroendocrine tumors on Aster’s liver, Alexandra Gangi, MD, director of the Division of Surgical Oncology and co-director of the Neuroendocrine Tumor Multidisciplinary Clinc, chose another minimally invasive approach: tumor embolization.

“We accessed the tumors with a catheter, through the artery in the groin,” Gangi said. “This allows us to block off the blood flow to the specific arteries that feed the tumors. This starves the tumors, and results in shrinking and tumor control.”

So far, Aster has avoided surgery and chemotherapy because of the nature of neuroendocrine tumors and the expertise of his care team in sequencing his therapies based on his sypmtoms.

“I think the difference between metastatic neuroendocrine tumors and most other types of gastrointestinal cancers is that we’re playing the long game,” Gangi said. “We often do the least invasive thing and save more aggressive options for when we really need them. These tumors tend to recur, but prognosis is generally good and patients can live a long time with them.”

Additional treatment or surgical procedures might be on the horizon, but today, Aster is doing well.

“We feel very fortunate that we were able to identify this as early as we did and intervene in the way that we did,” Hendifar said. “A few years ago, even six months ago, Ken wouldn't have been a candidate for minimally invasive valve replacements. He would have required open-heart surgery, and I'm not sure if the outcome would have been as good.”

Aster describes his current health as “great.”

“I just started cycling again in January, 13 months after the second valve replacement,” Aster said. “Now I'm doing a 25-mile ride in the hills two or three times a week with no problem. My heart feels as normal as can be.”

Cedars-Sinai Health Sciences University is advancing groundbreaking research and educating future leaders in medicine, biomedical sciences and allied health sciences. Learn more about the university.

The 52-year-old has always enjoyed a high-energy lifestyle, managing the intensity of producing films and television shows (Ladder 49, Flight Plan, Top Gear, Wheeler Dealers) by eating healthy, running and biking along the Los Angeles River. After his daughter was born in 2020, Nieminen assumed his constant exhaustion was the typical kind that comes with sleepless nights caring for a newborn. Still, he and his wife, Kaisa, found it odd that picking up his daughter left him depleted.

“My battery was constantly drained,” Nieminen said. “Being physically active all my life, it was quite alarming. Deteriorating this quickly when I’m just over 50 seemed sort of dramatic.”

Nieminen also noticed his heart seemed to beat too fast at times and occasionally it would skip a beat, so in 2023 he made an appointment with Cedars-Sinai cardiologist Ronit Zadikany, MD. Zadikany diagnosed him with atrial fibrillation, an irregular heart rhythm that occurs when the upper and lower chambers of the heart beat out of sync. The condition tends to worsen with time and can cause the heart to beat too slowly, too quickly or irregularly, impeding blood flow. Common symptoms include fatigue, heart palpitations, dizziness and reduced stamina. Left untreated, atrial fibrillation can cause a slew of cardiovascular complications—including stroke.

Nieminen’s cardiologist referred him to Christine M. Albert, MD, MPH, an expert in atrial fibrillation and chair of the Department of Cardiology in the Smidt Heart Institute. Albert recommended cardioversion, a procedure commonly used to reset the heart to a normal rhythm. The results made Nieminen feel like himself again, but only for a day. A second cardioversion combined with a medication known to work for many people also had temporary effects.

Albert was determined to find Nieminen a treatment that would have long-term results. She suggested he might benefit from catheter ablation, a procedure that destroys cells and creates a small scar within the heart, breaking up or insulating the electrical signals causing the heart to beat out of sync. She connected him with Michael Shehata, MD, a cardiac electrophysiologist in the Smidt Heart Institute.

Shehata was leading a clinical trial investigating a new catheter ablation called pulsed field ablation. Rather than create scars, pulsed field ablation targets heart cells involved in an abnormal heart rhythm.

Nieminen underwent the procedure in January 2024.

“When other options fail, this procedure can be life-changing for patients,” Shehata said.

Pulsed field ablation is done by threading a catheter through a vein in a patient’s leg until it reaches the top chambers of the heart. Once in place, a cardiologist sends a high-voltage electrical impulse through the catheter. The energy penetrates cell walls and destroys specific heart cells, preventing abnormal signals from causing an irregular heartbeat. The procedure takes 30 to 60 minutes.

“The energy is delivered specifically to heart cells without injuring nerve cells, smooth muscle cells, or other, healthy cells,” said Shehata, who is also director of the Interventional Electrophysiology Laboratory at the Smidt Heart Institute. “For some patients with atrial fibrillation, this procedure may be safer than conventional ablation procedures that destroy small areas of heart tissue.”

Following U.S. Food and Drug Administration approval of several pulsed field ablation systems, the procedure is now available for use outside of a clinical trial.

Advances in treatment couldn’t come at a better time. Atrial fibrillation is the most common type of irregular heartbeat and deaths related to the condition have been increasing for more than two decades, according to the U.S. Centers for Disease Control and Prevention.

Today, Nieminen is back to long runs and cycling through his neighborhood. He also works with local organizations to advocate for safe walking and biking paths in Los Angeles. Most importantly, he can now lift his daughter into the air like the high-energy dad he is.

A device that was implanted to record Nieminen’s heart rhythm shows proof of his progress: He has been free from atrial fibrillation since getting pulsed field ablation.

“Don’t hesitate to share with your doctors when something feels off because you feel like you’re being a hypochondriac or you think it’s too insignificant to bring up,” he said. “As you get older, it’s especially important to listen to your body, eat right and stay active, and that doesn’t necessarily mean doing a 10K. Everything your mom would tell you growing up: Stay active, eat healthy, get sleep and get checkups with your doctor. Mom knew what she was talking about.”

Read more on Cedars-Sinai Stories and Insights: Back Into Rhythm | Adjusting to an AFib Diagnosis

Injections of platelet-rich plasma made from a patient’s own blood are increasingly used to treat knee osteoarthritis—but their use is not widely accepted and the treatment does not work for everyone. Investigators from Cedars-Sinai Health Sciences University have taken the first steps toward predicting which patients will benefit.

With further study, their findings, published in the Orthopaedic Journal of Sports Medicine, could improve patient outcomes and guide development of next-generation treatments for the debilitating condition.

During the procedure, a patient’s blood is processed in a machine that separates plasma and platelets—a blood component essential for clotting. The concentrated platelet-rich plasma (PRP) is then injected into the affected knee to promote repair.

About 60% of patients in the study experienced reduced pain and better knee function after treatment, said Dmitriy Sheyn, PhD, associate professor of Orthopaedics and Surgery and corresponding author of the study.

“We found that patients whose pain and inflammation improved after treatment tended to have lower concentrations of specific cellular and protein biomarkers in their PRP, while patients who had poorer responses to treatment had higher concentrations,” said Sheyn, also a research scientist in the Board of Governors Regenerative Medicine Institute. “This suggests that the biological makeup of platelet-rich plasma varies between individuals and might influence how well the treatment works.”

The study represents the first attempt to understand how PRP works, said Bert Mandelbaum, MD, professor of Orthopaedics and senior author of the study.

“While this study is small and did not include a ‘placebo’ group that did not receive PRP, it is a first step toward identifying the active ingredients in the therapy so that we can design a complementary arthritis treatment based around them,” Mandelbaum said. “We are excited to continue this work.”  

Additional Cedars-Sinai authors include Lea Zila; Juliane D. Glaeser; Julia Sheyn; Giselle Kaneda; Jacob T. Wechsler; Parnika Karthik; Victoria Yu; Jasmine Galloway; Sarah Parker; Aleksandr Stotland; Catherine Bresee; Khosrowdad Salehi; Pablo Avalos, MD; Clive Svendsen, PhD; and Wafa Tawackoli, PhD.

The other author is Begonya Comin-Anduix.

Funding: This study was internally funded by Regenerative Orthobiologics Center and Precision Health Initiative.

Study Finds Hospital Addiction Consultation Service May Improve Outcomes at Low Cost

Helping hospitalized patients begin treatment for opioid use disorder may improve outcomes at a reasonable financial cost, according to a study co-led by investigators at Cedars-Sinai Health Sciences University.

The analysis, published in JAMA Network Open, suggests that the hospital-based addiction consultation service known as START (Substance Use Treatment and Recovery Team) is cost-effective and clinically effective, based on findings from a prior randomized trial.

Investigators used a computer-based model to analyze the clinical trial data and evaluate healthcare costs and patient outcomes over one year. Compared with patients who received standard or usual care, those who received START were more likely to begin treatment for opioid use disorder and connect with follow-up care after discharge. Compared with usual care, START use cost an additional $162 per patient and approximately $15,750 per additional year lived in good health—well below commonly accepted thresholds for cost-effectiveness.

“Hospitalization is a critical opportunity to begin treatment for opioid use disorder, yet most patients are discharged without it,” said Teryl Nuckols, MD, MSHS, director of the Division of Internal Medicine at Cedars-Sinai and the study’s senior author. “While new care models can be costly to implement, our findings suggest START delivers meaningful health benefits for a relatively modest additional investment—providing strong value for patients and health systems alike.”

The authors said additional research is needed to better understand how hospitals can overcome barriers to implementing START and similar addiction consultation services. This information can inform hospital leaders and healthcare policymakers who are making decisions about the role of addiction consultation services in the care of hospitalized patients with opioid use disorder.

Additional Cedars-Sinai authors include Itai Danovitch, MD.

Additional authors include Adeyemi Okunogbe, MBChB, PhD; Alexandra Peltz, MHS; and Allison J. Ober, PhD.

Funding/Support: This study was supported by grant U01TR002756-01A1 from the National Center for Advancing Translational Sciences and the National Institute on Drug Abuse.

Conflict of Interest Disclosures: Dr. Danovitch reported having equity from Bexson Biomedical and Workit Health outside the submitted work. Dr. Nuckols reported receiving grant 5 U01 FD005938-04 from U.S. Food and Drug Administration outside the submitted work. No other disclosures were reported.

Cedars-Sinai Health Sciences University is advancing groundbreaking research and educating future leaders in medicine, biomedical sciences and allied health sciences. Learn more about the university.

Andrew Hendifar, MD, professor of Medicine and medical director of the Cancer Clinical Trials Office and the Gastrointestinal Oncology Disease Research Group at Cedars-Sinai, was a principal investigator on the trial and a co-author of the study, which was sponsored by Revolution Medicines, makers of the new drug. He sat down with the Cedars-Sinai Newsroom to talk about the study results.

How does this new drug work?

The medication, called daraxonrasib, is the first drug that targets cancer-causing mutations in pancreas cells.

The drug targets a mutation in the KRAS gene, part of the RAS genetic family. KRAS mutations are present in 92% of pancreatic cancers. KRAS genes normally act as an “on-off” switch for cell growth. Mutated KRAS genes are stuck in the “on” position and send out a signal that causes cells to divide and grow uncontrollably, allowing cancer to form.

Daraxonrasib blocks the KRAS signal by fitting into a keyhole-type spot on the gene. That spot has a complex shape and is difficult to reach within the cell. The drug gets around this problem by using a “passenger protein” as a Trojan horse. When the cell allows this protein in, daraxonrasib tags along.

Why are these clinical trial results so groundbreaking?

There are no targeted treatments approved for pancreas cancer, and we haven’t had any significant progress for a long time. We've only come up with different chemotherapy combinations, and those are only moderately effective. This new treatment is staggeringly better than chemotherapy. Usually, when we think of an improvement in pancreatic cancer survival, we think of 25% improvement. This medication actually doubled survival in patients with advanced disease. We have patients who participated in the trial who are still alive, which is unheard of because the five-year survival rate for pancreatic cancer patients is only 13%-14%. If the drug is approved by the FDA, it will most likely become the new standard of care for advanced pancreatic cancer and could replace chemotherapy as a first-line treatment.

What comes next?

We are now testing the drug in patients with earlier-stage pancreatic cancer, prescribing it while their tumors are still operable and before their cancer spreads.

Could daraxonrasib be effective against other cancer types?

RAS mutations are one of the most common cancer-causing genetic mutations, and the drug is now being studied in several cancer types. I think it's going to work especially well in tumors that are primarily RAS driven, including colon cancer and lung cancer. It might also work in other cancer types in combination with drugs targeting other genetic mutations, but further research is needed.

How will this discovery change cancer science?

This is a win for the field. Until now we have been focused on immune therapies that might make tumors more vulnerable to the body’s immune system, and on finding new chemotherapy combinations that kill cancer cells.

This new treatment has given us a new focus, and I think it will spur a lot of scientific discovery over the next few years. There have only been a handful of KRAS researchers and their relevance to therapy was always questioned. That is about to change.

The most important next step for the field is to better understand the biology of cancer. We know that many pancreatic tumors will eventually become resistant to daraxonrasib, and we need to understand how this happens. We also need to identify additional genetic pathways and treatments that can target them. That’s how we will turn pancreas cancer from a deadly, deadly cancer into something we can manage—and one day, even cure.

Cedars-Sinai Health Sciences University is advancing groundbreaking research and educating future leaders in medicine, biomedical sciences and allied health sciences. Learn more about the university.

Smidt Heart Institute cardiologist Janet Wei, MD, is one of the authors of a maternal health report from the National Academies of Sciences, Engineering, and Medicine, a nonprofit organization that reviews published research and provides advice to the U.S. government. Wei, associate professor of Cardiology and Biomedical Sciences, sat down with the Cedars-Sinai Newsroom to explain how pregnancy affects women’s hearts.   

How does pregnancy increase cardiovascular risk?

Pregnancy acts as a stress test for the heart and can uncover, or even worsen, problems like high blood pressure and diabetes. During pregnancy, the heart must work harder to support a growing fetus, and cardiac stress often continues after delivery.

Cardiovascular disease is the leading cause of pregnancy-related death in the U.S., yet most of these deaths are preventable. The National Academies of Sciences, Engineering, and Medicine report on maternal health highlights that although 57% of cardiovascular-related deaths occur between seven days and one year postpartum, preventive care is often focused on the prenatal and immediate postpartum period.

What are two takeaways from the report?

The committee reviewed published medical research and gathered input from a wide range of stakeholders, including clinicians, professional societies, advocacy organizations and patients.

Several takeaways became clear. The report recommends, for example, that clinicians treat pregnant women with chronic hypertension so that their blood pressure is reduced to less than 140/90 millimeters of mercury.  This is because consistently elevated blood pressure during pregnancy can cause pregnancy complications and increase a woman’s risk for developing cardiovascular disease.

The new guidelines also recommended that clinicians caring for patients with postpartum hypertension or other hypertensive disorders give their patients home blood pressure monitors and use a program that allows the patients to report their readings. This way, clinicians can adjust treatment and set clear thresholds for action. 

Cedars-Sinai is already doing this through a postpartum blood pressure monitoring program that sends patients home with a blood pressure cuff and allows them to transmit readings to their care teams. (Kimberly Gregory, MD, MPH, director of the Division of Maternal-Fetal Medicine at Cedars-Sinai, served as an adviser to the National Academies committee that created the maternal health report.)

How often should women visit a doctor in the year after giving birth?

How frequently a woman should see her doctor during the postpartum period depends on her cardiovascular risk. 

Not every woman can easily see a doctor or health specialist—especially in rural areas or when cost is a concern. Therefore, the National Academies report recommends the Health Resources and Services Administration use its telehealth, rural health and maternal health programs to reduce geographic, financial and system barriers to preventive cardiovascular services.

What can pregnant women do to protect heart health?

The National Academies created a resource for women that includes the following advice:

Share your history. Tell your healthcare team your family history of heart disease, especially early heart attacks or strokes, and your pregnancy history, including any past complications.

Keep postpartum follow-up appointments on your calendar. It’s important not to miss these appointments because risk for complications continues through the first year after delivery.

Take warning signs seriously—trust your instincts. If something feels wrong during pregnancy or after birth, seek care right away and tell providers that you’re pregnant or that you gave birth recently.

Read more from Cedars-Sinai Stories and Insights: High Blood Pressure—What Women Need to Know

Younger people who experience sudden cardiac arrest are more likely to have a genetic cause than older people who experience it, according to new research from the

“If you have a family member who suffered sudden cardiac arrest, it is important to undergo genetic testing to determine if you harbor a genetic variant that increases your risk of sudden cardiac arrest or other heart conditions,” said Evan Kransdorf, MD, PhD, assistant professor of Cardiology in the Smidt Heart Institute and first author of the study. “For people who carry a variant linked to sudden cardiac arrest, a cardiologist can prescribe medications or lifestyle changes that can decrease the chances of experiencing this dangerous event.”

Sudden cardiac arrest, an electrical malfunction that causes the heart to beat very rapidly, is fatal in 90% of cases, according to the American Heart Association. The Cedars-Sinai Health Sciences University investigators found that 10% of people 29 and younger who have sudden cardiac arrest carry genetic variants linked with the condition.

The team analyzed blood samples from more than 3,000 people who experienced sudden cardiac arrest in Portland, Oregon, and Ventura County, California. The samples came from the ongoing Oregon Sudden Unexpected Death Study and the Ventura Prediction of Sudden Death in Multi-Ethnic Communities study—both created by Sumeet Chugh, MD, director of the Center for Cardiac Arrest Prevention in the Smidt Heart Institute, to improve understanding of the condition.

Investigators performed whole genome sequencing, which maps a person’s entire genetic code. They identified 15 genes in which damaging genetic variants can occur and disrupt the gene’s function and increase risk of sudden cardiac arrest. They found the prevalence of damaging genetic variants decreased with age:

• 10% of people age 29 and younger harbored a damaging genetic variant.
• 7% of people age 30-49 harbored a damaging genetic variant.
• 4% of people age 50-69 harbored a damaging genetic variant.
• 3% of people age 70 and older harbored a damaging genetic variant.

In older people, sudden cardiac arrest is more likely to be caused by a narrowed or blocked heart blood vessel rather than a heart condition caused by a damaging genetic variant, according to the investigators.

The investigators said more research will help uncover other genes linked to sudden cardiac arrest.

“This study is more representative of the U.S. population than other studies because it includes data from two communities rather than data from people already being seen at a medical center,” said Chugh, who is also vice dean and chief artificial intelligence health research officer at Cedars-Sinai and senior author of the study.

Additional Cedars-Sinai authors include Marco Mathias, BS; Kotoka Nakamura, PhD; Harpriya Chugh, BE, MSHS; David Nguyen, BS; Paul D. Pharoah, MD, PhD; and Kyndaron Reinier, MPH, PhD.

Other authors include Jonathan Tyrer, PhD; Zeynep Akdemir, PhD; Eric Boerwinkle, PhD; and Bing Yu, PhD. 

Funding: The study was funded by The National Institute of Health, NHLBI Grants R01HL145675 and R01HL147358; NIH DHHS Contracts HHSN268201700001I, HHSN268201700002I, HHSN268201700003I, HHSN268201700004I, HHSN268201700005I.

Read more from Cedars-Sinai Stories and Insights: Heart Attack, Cardiac Arrest, Heart Failure—What’s the Difference?

Alcohol‐associated liver disease, which is caused by chronic alcohol use, can lead to inflammation and scarring of the liver. In severe cases it can lead to liver failure, with some patients requiring a liver transplant. The condition accounts for nearly half of the liver-disease-related deaths in the U.S., according to the National Institutes of Health.

“We do not have effective therapies for alcohol‐associated liver disease,” said Shelly Lu, MD, the Women's Guild Chair in Gastroenterology and director of the Karsh Division of Gastroenterology and Hepatology. “Abstaining from alcohol can arrest this condition but this is often difficult to achieve. To save lives, we need to target drivers of alcohol-associated liver disease that promote inflammation and scarring. ”

Lu is co-corresponding author of a study, published in Hepatology, which connected a protein called FOXM1 with scarring and inflammation in alcohol‐associated liver disease. Another recent Cedars-Sinai study, published in Science Advances, showed that alcohol caused an enzyme known as SRC to alter the liver’s immune responses.

In Lu’s study, investigators examined alcohol-exposed human liver tissue samples and cells, and those of laboratory mice. They found that the FOXM1 protein controlled a network of genes and proteins that worked together to cause liver scarring and inflammation. FOXM1 is known to be involved in multiple liver diseases, including cancer. When the investigators suppressed the action of FOXM1, liver scarring was reversed.

“We found that FOXM1 is a key regulator of alcohol-associated liver disease progression and represents a promising target for therapeutic intervention,” Lu said.

The Science Advances study demonstrated how alcohol exposure—through the action of the enzyme SRC and the protein called UBC9—triggered inflammation and immune changes in the liver. When investigators used gene editing or enzymes to block SRC activity,  inflammation was reduced.

“The strong effect of enzymes suggests the possibility of therapeutic targets against alcohol‐associated liver disease,” said Maria Lauda Tomasi, PhD, associate professor of Medicine and Biomedical Sciences at Cedars-Sinai and the study’s co-corresponding author.

The findings also highlight UBC9 as a key regulator of the immune response, which could have implications beyond the liver for cancer and other inflammatory diseases, Tomasi said.

“These rigorous studies contribute greatly to our understanding of alcohol‐associated liver disease,” said David E. Cohen, MD, PhD, chair of the Department of Medicine. “The findings could open new pathways for the development of urgently needed treatments.”

Other Cedars-Sinai authors of the Hepatology study include Bing Yang, Liqing Lu, Jiaohong Wang, Lucía Barbier-Torres, Jing Zhang, Jyoti Chhimwal, Sonal Sinha, Brent Beadel, Guo Zhang, Takashi Tsuchiya, Maria Lauda Tomasi and Heping Yang. The other author was Ting Liu.

Funding: This work was supported by NIH grant R01AA026759 (Shelly C. Lu, Heping Yang, and Maria Lauda Tomasi).

Other Cedars-Sinai authors of the Science Advances study include Swati Chandla, Youngyi Lim, Andrea Floris, Michael Mazarei, Xi Yang, Takashi Tsuchiya, Manisha Dagar, Alfonso Darmawan, Monica Justo, Ramachandran Murali, Alexandra Gangi, Nirmala Mavila and Komal Ramani. The other author was Ivan Tomasi.

Funding: This work was supported by the National Institutes of Health, grant 

Cedars-Sinai Health Sciences University is advancing groundbreaking research and educating future leaders in medicine, biomedical sciences and allied health sciences. Learn more about the university.

The study, published in the Journal of Clinical Endocrinology & Metabolism, found that patients with hypothyroidism had more than double the risk of developing SIBO compared to those with normal thyroid function. The risk was even higher in patients with autoimmune thyroid disease, where the body’s immune system attacks the thyroid gland, but appeared lower in those receiving hormone treatment for the condition.

The findings offer insight into how specific changes in gut bacteria could contribute to disease beyond the gastrointestinal system.

“Studies like this remind us how interconnected the body’s systems are and the important role the microbiome plays in overall health,” said endocrinologist Ruchi Mathur, MD, director of Clinical Research and Clinical Operations for the Medically Associated Science and Technology (MAST) program and the study’s corresponding author.

Mathur sat down with the Cedars-Sinai Newsroom to share key takeaways from the investigation.

What did the study reveal about gut bacteria activity in patients with thyroid disease?

We found that patients with hypothyroidism had different patterns of bacteria in the small intestine compared with those without thyroid disease. In patients with both hypothyroidism and SIBO, we found Klebsiella bacteria dominated rather than the bacterial groups we more commonly see in SIBO. This suggests hypothyroidism may not only increase the risk of SIBO but may also influence the types of bacteria involved.

Could this mean a more severe form of SIBO?

Possibly, more research is needed to confirm this. Previous Cedars-Sinai research has shown that Klebsiella can disrupt the balance and interaction of bacteria in the small intestine more than some other bacterial groups.

How does thyroid hormone treatment affect SIBO risk?

One of the more interesting findings of our study was that patients receiving levothyroxine to treat their thyroid condition appeared to have a lower risk of developing SIBO compared with untreated patients. It is possible that thyroid hormone replacement affects gut motility, which may help reduce bacterial overgrowth in the small intestine. More research is needed, but the finding suggests thyroid treatment may influence digestive health in ways we are only beginning to understand.

Why is it important to study the small intestine directly?

Many microbiome studies rely on stool samples, but the bacteria found in stool can differ significantly from those living in the small intestine. The small intestine plays a central role in digestion, metabolism and hormone function, so studying it directly gives us a much more accurate picture of what may be happening in diseases such as hypothyroidism and SIBO. It also may help researchers identify future therapeutic targets.

What can physicians and patients learn from these new insights?

It is important to recognize the relationship between hypothyroidism and SIBO and address symptoms accordingly. If a patient with hypothyroidism is complaining of gastrointestinal symptoms such as bloating or altered bowel habits, their care team should consider evaluating them for SIBO. Likewise, if a patient presents with bloating, constipation or unexplained gastrointestinal symptoms, thyroid testing may also be appropriate.

Cedars-Sinai Health Sciences University is advancing groundbreaking research and educating future leaders in medicine, biomedical sciences and allied health sciences. Learn more about the university.

The new tool, called Path2Space, predicts gene expression across the tumor area based on digital images of biopsy slides, which contain thin slices of tumor tissue that can be examined under a microscope.

Because tumors do not have the same composition and gene expression throughout, Path2Space predicts what is known as “spatial” gene expression, estimating it at many different points within the tumor. The process takes only minutes and costs significantly less than conventional spatial gene expression profiling, which typically takes several weeks and costs thousands of dollars.

“This tool makes two major contributions,” said Eytan Ruppin, MD, PhD, deputy director of the Translational Research Institute at Cedars-Sinai and senior author of the study. “It will enable us and others to study larger datasets and understand the spatial structure of tumors. But what really motivates me is that, if we can successfully validate the tool in clinical trials, it could improve cancer care for patients.”  

Investigators “trained” Path2Space using data from a large group of patients with breast cancer, where the biopsy slides and spatial sequencing were both available. They then tested the tool on three additional patient datasets to validate its performance.

“For each sample, we looked at the actual, measured gene expression and compared it with our tool’s prediction,” said Eldad Shulman, PhD, co-first author of the study and a research fellow at the National Cancer Institute, who will soon join Ruppin's lab as a research scientist. “For each sample, we predicted the spatial expression of almost 5,000 genes, and the predictions matched the measured expression well across all three patient groups.”

Path2Space is also designed to help scientists discover new biomarkers that could guide treatment decisions and identify patients at higher risk of poor outcomes.  

“The tool looks at characteristics within the tumor, such as whether a gene is expressed in some areas of the tumor and not others,” said Emma Campagnolo, co-first author of the study and a research fellow in Ruppin’s lab. “We found specific spatial patterns of gene activity in tumors that predict how patients respond to treatment.”

Identifying spatial biomarkers is challenging, Shulman said, because the high cost of spatial profiling by traditional methods means very little of this data is available.

“Before we developed Path2Space, the largest cohort we could find to study the spatial organization of the tumor environment was about 30 patients,” Shulman said. “With this tool, we can study slides from thousands of patients. Path2Space is tapping into the potential of spatial biology in a way that has not been possible until now.”

Path2Space could be applied to other cancer types once it is trained on the correct data, and the lab is finalizing a study applying it to head and neck cancer, Campagnolo said. The team is also working to make the tool more precise. It currently looks at groups of 10 to 20 cells together, and the goal is to eventually be able to assess individual cells.  

“With the help of clinical collaborators, we next want to bring Path2Space into clinical trials,” Ruppin said. “It represents an exciting development in a growing field and has to be tested carefully. But we are hopeful that it could make an impactful contribution to science and to patient care.”

Robert Figlin, MD, interim director of Cedars-Sinai Cancer, noted that translational research is a hallmark of the institution.

“The development of tools that apply leading-edge science to patient care is the best way to serve our patients—and to improve cancer care on a global scale,” Figlin said.

Additional Cedars-Sinai authors include Yuan Yuan, Karine Sargsyan, and Simon R.V. Knott.

Other authors include Roshan Lodha, Youngmin Chung, Amos Stemmer, Thomas Cantore, Beibei Ru, Tian-Gen Chang, Sumona Biswas, Saugato Rahman Dhruba, Sumeet Patiyal, Sushant Patkar, Andrew Wang, Ranjan K. Barman, Chuhan Wang, Rohit Paul, Sarath Chandra Kalisetty, Tom Hu, MacLean P. Nasrallah, Ellis Patrick, Jean Yang, Amy Plotkin, Padma Sheila Rajagopal, Stephen-John Sammut, Stanley Lipkowitz, Peng Jiang, Carlos Caldas, Kenneth Aldape, Joo Sang Lee, and Danh-Tai Hoang.

Funding: This research was supported by the Intramural Research Program of the NIH, NCI, and the Center for Cancer Research. The contributions of the NIH authors were made as part of their official duties, as NIH federal employees are in compliance with agency policy requirements and are considered works of the U.S. government. This research was also partially supported by a grant of the Korea-United States Collaborative Research Fund, funded by the Ministry of Science and ICT and the Ministry of Health and Welfare, Republic of Korea (grant number: RS-2024-00468417; Y.C. and J.S.L.), and by an Institute of Information & Communications Technology Planning & Evaluation (IITP) grant funded by the Korea government (MSIT) (RS-2019-II190421, AI Graduate School Support Program, Sungkyunkwan University; Y.C. and J.S.L.). This work has utilized the computational resources of the NIH HPC Biowulf cluster.

Competing interests: E.D.S., E.M.C. and E.R. are listed as inventors on a provisional patent (application no. 63/703,060, United States, 2024) filed based on the methodology outlined in this study. E.R is (non-paid) member of the scientific advisory boards of Pangea Biomed (divested), GSK Oncology and the ProCan project. E.R is a founder of MedAware Ltd. The other authors declare no competing interests.

Cedars-Sinai Health Sciences University is advancing groundbreaking research and educating future leaders in medicine, biomedical sciences and allied health sciences. Learn more about the university.

Some Breast Cancer Survivors Need Closer Heart Disease Monitoring

The racial makeup and socioeconomic status of early-stage breast cancer patients could offer clues about their risk for heart disease, the leading cause of death among breast cancer survivors. Results of a study led by a Cedars-Sinai breast oncologist and published in npj Breast Cancer identified several groups of patients who could benefit from closer monitoring after a breast cancer diagnosis.

“Our study found that—regardless of other medical conditions or the type of cancer treatment received—Black breast cancer survivors and patients living in areas with the lowest per capita income had a higher risk of heart failure over time compared with white patients or those living in areas with the highest per capita income,” said Karissa Britten, MD, breast medical oncologist, member of Cedars-Sinai Cancer and corresponding author of the study.

Looking at data from more than 200,000 breast cancer patients in a National Cancer Institute database, investigators also found that patients of Black, Hispanic, and American Indian/Alaskan Native descent had more advanced and more aggressive tumors, compared with white or Asian American/Pacific Islander patients. Patients from lower-income areas or with lower levels of education also were more likely to have these higher-risk tumors.

“Our Cardio-Oncology Research Program was established to study cardiovascular disease in patients with cancer,” said Robert Figlin, MD, interim director of Cedars-Sinai Cancer. “Our goal is to better understand the risks involved and to develop novel therapies to address them.”

Britten said that no evidence-based guidelines currently exist for heart monitoring of high-risk patients after a diagnosis of early-stage breast cancer, but the study findings point to an opportunity for targeted monitoring and early intervention that could save lives.

Additional authors include Marla Lipsyc-Sharf, Eric H. Yang, Susan McCloskey, Mina S. Sedrak, Mediget Teshome, Julia LaBarbera, Aditya Bardia, and Nicholas McAndrew.

Funding: The collection of cancer incidence data used in this study was supported by the California Department of Public Health pursuant to California Health and Safety Code Section 103885; Centers for Disease Control and Prevention’s (CDC) National Program of Cancer Registries, under cooperative agreement 1NU58DP007156; the National Cancer Institute’s Surveillance, Epidemiology and End Results Program under contract HHSN261201800032I awarded to the University of California, San Francisco, contract HHSN261201800015I awarded to the University of Southern California, and contract HHSN261201800009I awarded to the Public Health Institute.

Use of Hepatitis C-Positive Donors Reduces Pancreas Transplant Wait Times

Researchers at Cedars-Sinai Health Sciences University have discovered that utilizing organs from donors who are hepatitis C virus-positive (HCV+) can greatly shorten wait times for those awaiting pancreas transplants. According to their study published in the American Journal of Transplantation, patients receiving HCV+ organs experienced an average reduction of 117 days in wait time, all while maintaining comparable safety and organ function to those receiving organs from HCV-negative donors.

The study also found that transplant centers can safely handle infections passed from donors to recipients by using direct-acting antiviral therapies that cure hepatitis C, a viral infection that can cause severe liver damage. This method decreases organ wastage and increases the availability of organs for patients, who often face complications while waiting for transplantation.

“By maximizing the potential of available organs, we can transplant more patients and, ultimately, extend more lives,” said Todd Brennan, MD, professor of Surgery at Cedars-Sinai Comprehensive Transplant Center and corresponding author of the study. "Our goal is for this research to help guide national guidelines on donor utilization and expand access to transplantation.”

Additional Cedars-Sinai authors include Tiffany Lim, Yujie Cui, Kambiz Kosari, Georgios Voidonikolas, Tsuyoshi Todo, Justin A. Steggerda, Steven A. Wisel, and Irene K. Kim

Other authors include Gabriel E. Nissen and Olyvia S. Wang.

Novel In-Hospital Screening Method Detects Cognitive Issues

Over 40% of older people admitted to U.S. hospitals have dementia, yet only half of them have been diagnosed with memory and cognitive difficulty. Cedars-Sinai Health Sciences University investigators have developed a comprehensive screening method that identifies previously undiagnosed cognitive impairment and dementia in hospitalized patients. Their findings were published in the Journal of the American Geriatrics Society.

Cognitive impairment, which is more common in older adults, involves challenges with a person’s ability to think, learn, remember and make decisions. In people with dementia, these problems are severe enough to interfere with daily life. Both conditions frequently go undetected, which can adversely affect patient care in hospital settings.

“Early recognition of cognitive issues is critical to improving hospital care, optimizing outcomes, and proactive discharge planning for cognitively impaired patients, who are at increased risk for falling, behavioral issues and hospital readmission,” said Zaldy S. Tan, MD, MPH, medical director of the Jona Goldrich Center for Alzheimer’s and Memory Disorders at Cedars-Sinai and corresponding author of the study. “And yet, cognitive screening of patients remains rare in U.S. hospitals because they lack effective strategies for implementing it.”

The new screening method includes brief cognitive assessments administered by nursing staff to patients over the age 65 who are admitted to the hospital, coupled with an algorithmic tool in the electronic health record that flags patients with cognitive impairment and dementia. When this system was implemented across more than 11,000 hospital admissions, it resulted in the cognitive screening of more than 80% of eligible older adults. It detected previously unrecognized cognitive impairment in 9% of those patients and undiagnosed dementia in 4.3%. Black and older (over 85 years) patients were more likely to be identified to have undiagnosed dementia compared with younger and white patients.

“Our screening approach demonstrated the potential to equitably capture cognitive impairment at the point of hospital admission, allowing for interventions to optimize the care for all vulnerable patients,” Tan said.

Additional Cedars-Sinai authors include Nabeel Qureshi, Nancy L. Sicotte, Drew Hirsch, Cameron Escovedo, Erica Spivack, Mary C. Nasmyth, Mitzi Gonzales, Sarah A. Kremen, Teryl K. Nuckols, Janae McFadden and Pamela R. Roberts.

Other authors include John Mafi.

Funding: The study was supported through internal institutional funding. Data collection was supported by NIH National Center for Advancing Translational Science (NCATS) UCLA CTSI Grant Number UL1TR001881.

Proteins Found in Cancer Extracellular Vesicles Could Guide Drug Development

Cancer cells release tiny biological packages called extracellular vesicles (EVs) that help tumors grow and spread. A team led by Cedars-Sinai Health Sciences University investigators has now connected certain proteins carried in these EVs with poor patient outcomes in multiple cancer types.

Their findings were published in the Journal of Extracellular Vesicles.

“By identifying these proteins, we aim to uncover new targets for drugs that could be used to treat many types of cancer,” said Sungyong You, PhD, professor of Urology and Computational Biomedicine and corresponding author of the study.

Investigators analyzed data from more than 2,200 patients with 12 different cancer types. They linked 26 specific proteins present in EVs from these patients to poor survival. The standout across multiple tumor types was a protein called PTK7. The analysis also showed that blocking PTK7 effectively stops cancer cell growth, highlighting it as a promising target for therapies.

“These findings provide a powerful new blueprint for using EV data to guide cancer drug testing and applications,” said Robert Figlin, MD, interim director of Cedars-Sinai Cancer. “The proteins identified can guide the development of novel therapies and the repurposing of existing drugs for new cancer treatments.”

Additional Cedars-Sinai authors include Jina Kim and Hyoyoung Kim.

Other authors include Su Yeon Yeon, Kyerim Choi, Hojung Kim and Daehee Hwang.

Funding: This research was funded by National Institutes of Health R01CA277530 (H.R.T., Y.Z., V.G.A., J.D.Y., S.Y.), R01CA255727 (Y.Z., H.R.T., S.Y.), R01CA253651 (H.R.T., V.G.A., S.Y.), R01CA253651-04S1 (Y.Z., H.R.T., S.Y.), R01CA246304 (H.R.T., V.G.A., S.Y.), P01CA278732 (S.Y.), and The Samuel Oschin Comprehensive Cancer Institute (SOCCI) at Cedars-Sinai Medical Center through 2024 Program Project Grant (PPG) Team Science Award (S.Y.).

Cedars-Sinai Health Sciences University is advancing groundbreaking research and educating future leaders in medicine, biomedical sciences and allied health sciences. Learn more about the university.

The early-stage international study, published in the journal Nature Medicine, focused on removing a harmful protein from a mother’s blood.

Preeclampsia is marked by high blood pressure that can quickly become life-threatening. In its most severe early form—before 34 weeks of pregnancy—physicians frequently must deliver babies prematurely to protect the mother, even though early delivery can pose significant risks for the infant. The method tested by investigators was found to safely extend pregnancy, giving babies more time to develop before birth.

“Even a few extra days in the womb can make a meaningful difference in outcomes for premature infants,” said co-corresponding study author Ananth Karumanchi, MD, professor of Medicine, director of the Renovascular Research Center and the Medallion Chair in Vascular Biology at Cedars-Sinai. “We found a way to potentially buy that time safely. Our approach could shift how we manage very early preeclampsia.”

The approach focuses on a protein called sFlt-1, which is produced by the placenta and known to damage blood vessels and drive preeclampsia symptoms. Investigators engineered a specialized immune protein that binds to sFlt-1 and incorporated it into a blood-filtering device. Using a process called extracorporeal apheresis—similar to kidney dialysis—they were able to filter the mother’s blood and remove excess sFlt-1 without affecting other essential blood components.

The treatment was evaluated in 16 women. Their blood pressure improved, their babies continued to grow normally during treatment, and they remained pregnant for an average of 10 additional days—more than double the time seen in untreated patients.

“Right now, the only way to cure preeclampsia and protect the life and health of the mother is to deliver the baby,” said Sarah Kilpatrick, MD, PhD, an expert in maternal-fetal medicine and chair of the Department of Obstetrics and Gynecology at Cedars-Sinai. “That puts very premature infants at high risk. This approach could give clinicians more flexibility in managing these high-risk cases.”

Researchers say the treatment is notable also because it removes a harmful factor rather than introducing new drugs, potentially reducing the risk of side effects. However, they note that despite the small study’s positive results, the treatment is experimental and needs to be tested in larger clinical trials.

“Our goal was to directly target one of the root causes of preeclampsia,” said the study’s co-corresponding author Ravi Thadhani, MD, MPH, executive vice president of Clinical Affairs, chief medical officer for Cedars-Sinai Medical Center and Cedars-Sinai Health System. “By lowering sFLt-1, we were able to stabilize patients and extend pregnancy—a meaningful and exciting step forward.”

Additional Cedars-Sinai authors include Agnes Lo.

Other authors include Thomas F. Hiemstra, Manu Vatish, Holger Stepan, Ana Sofia Cerdeira, Jeremy Brockelsby, Tim James, Massimiliano Lia, Alissa Cornelis, Elena Krause, Martin R. Spath, Berthold Grüttner, Polina Todorova, Henning Hagmann, Kristen R. Yeung, Bei Xu, Scott Heffernan, Suzanne Pears, Richard Waugh, John Thompson, Jim Iliopoulos, Neroli Sunderland, Murray Killingsworth, Angela Makris, Annemarie Hennessy, Adelene Y. Tan, Paul Kussie, Yuchiao Chang, Linda Hanssens, Stefan Miltenyi and Thomas Benzing.

Funding: This work was supported by Miltenyi Biomedicine and Aggamin Pharmaceuticals.

Competing Interests: R.T. and S.A.K. are co-inventors on multiple biomarker patents related to preeclampsia that have been out-licensed to several companies (Thermo Fisher Scientific, Beckman Coulter, Siemens and Roche) and report financial interest in Aggamin Pharmaceuticals and serving as a consultant to Comanche Biopharma. R.T. and S.A.K. are named as co-inventors on a provisional patent held by Cedars-Sinai Medical Center on a novel lateral-flow diagnostic assay for use in preeclampsia and related conditions. A.H. is an advisor to Comanche Biopharma. A.Y.T. and P.K. are employees of Aggamin.

Pharmaceuticals. L.H. is an employee of, and S.M. is the founder of, Miltenyi Biomedicine. All other authors disclose no conflicts. These financial interests have been disclosed in accordance with journal policies.

Cedars-Sinai Health Sciences University is advancing groundbreaking research and educating future leaders in medicine, biomedical sciences and allied health sciences. Learn more about the university.

But is agentic AI smart enough to replace actual scientists?

The Cedars-Sinai Newsroom sat down for a conversation with Jason Moore, PhD, chair of the Department of Computational Biomedicine at Cedars-Sinai, to tackle the pluses and minuses of agentic AI. Moore is corresponding author of a new paper, published in Nature Biotechnology, that examines where agentic AI is today and where it is headed.

What is agentic AI? Why is it called ‘in silico team science’?

Conducting biomedical research requires a team of specialists with expertise in different aspects of the medical issue being studied, from physiology to data collection and analysis, study design and writing. 

Agentic AI replicates this approach in a computer (in silico) by coordinating the activities of a “team” of AI solutions dedicated to completing specific tasks.

How does agentic AI help biomedical scientists?

As a researcher, I have a lot more ideas than I can actually pursue in my laboratory. Agentic AI is opening the door for me to explore more scientific questions than I otherwise could. It has allowed researchers in my lab to complete complex software-engineering and computer-programming projects in days rather than months, and we're seeing mind-boggling levels of productivity and efficiency.

These benefits are coming along at a particularly useful time. As the healthcare industry faces rising costs and reduced reimbursements, agentic AI can help labs be more efficient and survive with smaller teams.

Does this mean agentic AI will replace human scientists?

There's a lot of discussion about this in the AI community. I don't yet have confidence that AI can fully replace anybody in my research lab—and maybe it never will.

Humans do many things that AI may not be good at, such as managing people, displaying emotional empathy, and coming up with new hypotheses and creative solutions to problems. Those things are important if you want a research lab that functions well.

Trust is also a barrier. We know how to trust a human collaborator, but with potentially dozens of AI agents doing very complex things very rapidly, how do you know what they're doing? How can you be sure that what they've done is accurate?

From a broader perspective, how do we design ethical guardrails that ensure we put the human subjects of our scientific research first? And how do we find an environmentally sound way to provide the enormous amount of energy to fuel the computing power that AI requires?

Given these challenges, what do you view as the future of agentic AI?

The genie's out of the bottle. This technology is here, and it’s going to affect absolutely everything we do in our professional and personal lives. It is going to turn things upside down.

The exciting thing for biomedical science is that agentic AI will allow each person to be 10 or 20 or 100 times more efficient. And assigning tasks to AI allows us to focus more on the human skills, the creativity and the emotional side of what we do. It has the potential to accelerate scientific discoveries and the translation of those discoveries into better healthcare practices.

I try not to make specific predictions because all of this is moving so quickly and unpredictably. But I think the one prediction I can make about agentic AI is that everything's going to be different a year—or even six months—from now.

Cedars-Sinai Health Sciences University is advancing groundbreaking research and educating future leaders in medicine, biomedical sciences and allied health sciences. Learn more about the university.

The study, “Real-World Outcomes of Transcatheter Tricuspid Valve Replacement: Analysis From the STS/ACC TVT Registry,” published in the Journal of the American Medical Association.

“These findings show that transcatheter tricuspid valve replacement is translating well from the clinical trial setting into routine practice across the United States,” said Raj Makkar, MD, vice president of Cardiovascular Innovation and Intervention at Cedars-Sinai, the Karsh Distinguished Chair in Interventional Cardiology in the Smidt Heart Institute, and corresponding author of the study. “In a large, older and medically complex patient population, we saw very high procedural success, near-complete elimination of tricuspid regurgitation, and rapid improvement in how patients feel and function.”

Tricuspid regurgitation occurs when the tricuspid valve does not close properly, allowing blood to flow backward in the heart. The condition is common in older adults and can lead to worsening heart failure symptoms, repeated hospitalization and increased risk of death.

Historically, open-heart surgery was often the only treatment option for this condition, but many older patients were not candidates because of age or other medical problems. Today, transcatheter tricuspid valve replacement offers a less invasive alternative in which doctors replace the damaged valve using a catheter, or tube, threaded through a blood vessel.

Researchers analyzed 1,034 attempted TTVR procedures performed between February 2024 and March 2025 at 82 medical centers across the U.S. The average patient age was 77.

The analysis found that more than 98% of patients had the valves successfully implanted. At 30 days post-procedure, more than 97% of patients had their condition improve to mild or minimal tricuspid regurgitation, and patients reported substantial improvement in symptoms, physical and social function, and quality of life.

Study authors note that early real-world outcomes were consistent with results from the TRISCEND II randomized trial of TTVR. Patients in this new study, however, experienced lower incidence of bleeding and heart block requiring electronic pacemaker implantation than patients participating in TRISCEND II. The current study also found that outcomes were generally consistent in patients with and without preexisting cardiac implantable electronic devices such as pacemakers, an important finding because these devices are common in patients with severe tricuspid valve disease.

“For patients with severe tricuspid regurgitation, treatment options have historically been limited, especially when surgery carries high risk,” said Aakriti Gupta, MD, assistant professor of Cardiology and study author. “What is especially encouraging here is that in real-world care, not just in a randomized trial, patients experienced meaningful improvement in symptoms and quality of life within only 30 days.”

Investigators said the results support the growing role of TTVR as a treatment option for patients with severe tricuspid regurgitation and highlight the importance of continued follow-up to understand longer-term outcomes.

Moody Makar, MD, associate professor of Anesthesiology at Cedars-Sinai, is also an author of the study.

Additional authors include Brian P. O’Neill, MD; Christina Lalani, MD; Rahul Sharma, MBBS; Pradeep Yadev, MD; Tiberio M. Frisoli, MD; Vinod Thourani, MD; Mackram F. Eleid, MD; James Lee, MD; Vasilis C. Babaliaros, MD; Christiane Haeffele, MD, MPH; Tanvir J. Bajwa, MD; Peter Flueckiger, MD; Robert J. Cubeddu, MD; Laura J. Davidson, MD; Ratnasari Padang, MBBS, PhD; Pedro Villablanca Spinetto, MD; Suhail Allaqaband, MD; Akhil Narang, MD; Mathew Williams, MD; Patrick Gleason, MD; Gilbert H.L. Tang, MD; Sahil Khera, MD; John P. Vavalle, MD; Isida Byku, MD; Jeremiah P. Depta, MD; Santiago Garcia, MD; Samir Kapadia, MD; Alan Zajarias, MD; Jake M. Chanin, MD; Susheel K. Kodali, MD; Howard C. Herrmann, MD; M. Andrew Morse, MD; George Petrossian, MD; Joseph A. Sivak, MD; Rebecca T. Hahn, MD; Yang Song, PhD; Martin B. Leon, MD; Robert W. Yeh, MD, MSc; Charles J. Davidson, MD.

The study was funded by Edwards Lifesciences.

Cedars-Sinai Health Sciences University is advancing groundbreaking research and educating future leaders in medicine, biomedical sciences and allied health sciences. Learn more about the university.

The findings, published in Communications Medicine, are based on nearly two decades of electronic health records from more than 650,000 U.S. adults with IBS, making it the largest real-world study to examine the long-term safety of IBS treatments.

IBS is a chronic gastrointestinal condition affecting about 10% of the U.S. population. There is no cure, but dietary modifications, behavioral therapy and medications can help manage symptoms.

“Many patients are diagnosed with IBS at a young age and may remain on medications for years,” said Ali Rezaie, MD, medical director of the GI Motility Program at Cedars-Sinai and senior author of the study. “However, most clinical trials of these medications last less than a year, so we know very little about their long-term safety. This study begins to address that gap.”

Researchers assessed patients taking Food and Drug Administration-approved IBS medications, as well as antidepressants, antispasmodics and opioid-based antidiarrheal drugs, such as loperamide and diphenoxylate—widely used and recommended in IBS care. They found that long-term antidepressant use was associated with a 35% higher risk of death, and that loperamide and diphenoxylate use were associated with roughly double the risk of death.

The study does not establish that these medications directly cause death; rather, the observed associations may reflect higher rates of adverse outcomes, such as cardiovascular events, falls and stroke, which were more frequent among exposed patients.

Although antidepressants are not FDA-approved for IBS, they are commonly prescribed for IBS patients to help reduce pain, calm symptoms and make the condition easier to manage. The study found that other recommended treatments, including FDA-approved medications and antispasmodics, were not associated with increased mortality risk.

Researchers emphasized that while the increase in risk is significant and may sound concerning, the overall risk to any individual patient is small.

“IBS patients should not panic, but they do need to understand and weigh the small but meaningful risks when considering long-term treatments,” said Rezaie, the director of Bioinformatics at the Medically Associated Science and Technology (MAST) Program at Cedars-Sinai. “Patients should speak with their healthcare provider about the safest and most effective options for managing their symptoms.”

Rezaie said more research is needed to confirm these findings and identify which patients may be at greatest risk. He also called for future treatment guidelines to better address the long-term safety of medications commonly used to manage IBS.

In the meantime, he emphasized a more personalized approach to IBS patient care.

“Treatment for IBS patients should focus on identifying the underlying causes and using the safest, evidence-based options available rather than relying on a single class of medications for long-term management,” Rezaie said.

Additional Cedars-Sinai authors include Sepideh Mehravar, MD, Yee Hui Yeo, MD, and Mark Pimentel, MD.

Other authors include Parnian Naji, MD, Wee Han Ng, Nils Burger, PhD, and Will Takakura, MD.

Conflicts of Interest: Mark Pimentel is also a consultant for and received grant support from Bausch Health. Ali Rezaie reports serving as a consultant for Bausch Health and Ardelyx. In addition, Cedars-Sinai Medical Center has a licensing agreement with Gemelli Biotech. Ali Rezaie and Mark Pimentel have equity in Gemelli Biotech and Good LFE. The remaining authors disclose no conflicts.

Cedars-Sinai Health Sciences University is advancing groundbreaking research and educating future leaders in medicine, biomedical sciences and allied health sciences. Learn more about the university.

A New Algorithm Could Improve Location of Lifesaving Devices

Cedars-Sinai Health Sciences University investigators and colleagues created an algorithm designed to use data on sudden cardiac arrests to determine the best public locations for lifesaving devices called automated external defibrillators. Their findings were published in IJC Heart & Vasculature.

Known as AEDs, the portable devices deliver an electrical shock, with an aim to restart the heart when it stops beating due to sudden cardiac arrest. Sudden cardiac arrest is common and usually fatal when it happens somewhere other than a hospital.

“Research shows that the sooner a bystander can locate and use an AED, the higher the likelihood that the person experiencing sudden cardiac arrest survives,” said Sumeet Chugh, MD, vice dean and chief AI Health Research Officer at Cedars-Sinai, and senior author of the paper.

The investigators reviewed data on incidents of sudden cardiac arrest in Ventura County, California, and Multnomah County, Oregon, that took place between 2012 and 2023. The algorithm they created identified clusters of three or more incidents that occurred within a 100-meter radius of each other, and proposed AED locations within 200 meters of where these clusters occurred. 

Future studies will be needed to determine whether the algorithm is an improvement over current AED location strategies, the investigators said.

“These community-based studies are a huge team effort that involves ongoing collaborations with colleagues in emergency medical services and the fire department,” said Chugh, who is also director of the Center for Cardiac Arrest Prevention in the Smidt Heart Institute. “We hope researchers use this algorithm to study how the placement of AEDs reduces deaths from sudden cardiac arrest.”

Cedars-Sinai investigator Elizabeth Heckard, MS, is first author of the paper. Additional Cedars-Sinai authors include Harpriya Chugh, BE, MSHS, and Kyndaron Reinier, PhD, MPH.

Other authors include Katy Hadduck, Bryan McNally, Ali Sovari, Jonathan Jui, and Angelo Salvucci.

Cedars-Sinai Studies Pharmacist-Led Transitions-of-Care in Older Adults

Older hospitalized patients who struggled with taking their medications correctly were 10% less likely to need to return to the hospital if they had a pharmacist’s help at discharge, according to a new multisite clinical trial based at Cedars-Sinai. But the findings, published in JAMA Network Open, found the extra help didn’t significantly reduce unplanned hospital visits for the rest of those 55 and older.

The trial included more than 6,000 hospitalized older adults on high-risk or multiple medications, randomly assigning some to receive special pharmacist-led review of their medications and follow-up based on any issues identified. Investigators tracked patients’ hospital readmissions and emergency department visits for 30 days after discharge.

“The study suggests that pharmacist-led care could be beneficial for certain patients,” said Joshua Pevnick, MD, MSHS, co-director of the Cedars-Sinai Division of Clinical Informatics, associate professor of Medicine and corresponding author of the study. “With this new data, we encourage hospital care teams to ensure they support patients with low medication adherence and understanding, as they likely would benefit most from the efforts of our strong pharmacy transitions-of-care team.”

Other Cedars-Sinai authors include An T. Nguyen, OTD, OTR/L, BCG; Kallie Amer, PharmD, BCPS; Carl T. Berdahl, MD, MS; Galen Cook Wiens, MS; Hiroshi Gotanda, MD, PhD; James Guan, PharmD, BCPS; Andrew J. Henreid, MS, MPH; Donna W. Leang, PharmD, MSHS, BCPS; Yervant Malkhasian, PharmD; Teryl K. Nuckols, MD, MSHS; Audrienne S. Ortiz, PharmD, BCPS; Emily Phung, PharmD, BCPS; Nabeel Qureshi, PhD, MPH; Rita Shane, PharmD; and Shirley Wu, PharmD, BCPS.

Other authors include Korey Kennelty, PharmD, MS, PhD, BCGP, John Fanikos, RPh, MBA; Julie Fiskio; Michelle S. Keller, PhD, MPH; Eunji M. Ko, PharmD; Lina Matta, PharmD, MPH, BCPS; Dylan Moriarty, PharmD, BCACP, BCGP; Logan Murry, PharmD, PhD; Annie Muske, PharmD; Onyeche Oche, RPh, PhD, MBA-HCA; and Jeffrey L. Schnipper, MD, MPH, MHM on behalf of the PHARM-DC Group.

Funding support for this study was provided by the National Institutes of Health, National Institute on Aging, grant number R01AG058911 (to Joshua Pevnick). Additional funding support was provided by the UCLA Clinical and Translational Science Institute under grant number UL1TR001881 and the American Society of Health-System Pharmacists Research and Education Foundation.

Scientists Target Key Protein Duo Driving Colon, Liver Cancer

Cedars-Sinai Health Sciences University investigators have identified a drug-like compound that prevents two proteins from working together to promote the growth of colorectal and liver cancer. Findings from the preclinical study were published in Cell Death & Disease.

Investigators focused on the proteins GIT1 and MAT2B, which are found at unusually high levels in these cancers. The proteins partner to form a “scaffolding” that drives cancer growth. The team discovered that a compound called C3 targets GIT1 and disrupts this structure. The disruption slows cancer cell growth and triggers cancer cell death, which helps prevent the cancer from spreading.

Colorectal cancer is among the most diagnosed cancers, and its spread to the liver is a common, serious and life-threatening complication.

“We were pleased to find a promising drug candidate that attacks colon and liver cancers simultaneously,” said Shelly Lu, MD, the Women’s Guild Chair in Gastroenterology, director of the Karsh Division of Gastroenterology and Hepatology at Cedars-Sinai, and the study’s corresponding author. “And because GIT1 is overactive in many cancers, this discovery could have broad and powerful applications in cancer treatment.”

The next step is to refine the compound to improve its effectiveness.

In related research, Lu, a member of Cedars-Sinai Cancer, and Cedars-Sinai investigators recently uncovered another way colorectal cancer spreads. They found that cancer cells release two forms of an enzyme called MATα2 that work together to weaken the liver’s natural defenses, which helps cancer spread to the liver and survive there. The findings suggest that blocking this process could offer another promising future treatment approach.

Additional Cedars-Sinai authors include Hui Peng, Jyoti Chhimwal, Wei Fan, Jiaohong Wang, Lucia Barbier-Torres, Sonal Sinha, Avradip Chatterjee, Yi Zhang, Maria Lauda Tomasi and Ramachandran Murali.

Additional authors include Jose M. Mato.

Funding: The work was supported by NIH grant P01CA233452 (SC Lu, ML Tomasi), Plan Nacional of I+D SAF2017-88041-R (JM Mato).

Disclosures: SCL and RM have filed a patent for small molecule inhibitors of GIT1 (Title: COMPOUNDS AND METHODS FOR TREATING CANCERS; Application No. 63/422,672; Filed: Nov. 4, 2022).  

Cedars-Sinai Creates First Working Model of Specialized Gut Cells

Cedars-Sinai Health Sciences University investigators have for the first time created human intestinal organoids that include functional Paneth cells, a specialized cell type that is found in the inner lining of the intestine. This achievement, published in Cellular and Molecular Gastroenterology and Hepatology, facilitates study of the cells’ role in health and disease and opens new opportunities for understanding gastrointestinal disorders.

Organoids are tiny groups of cells, grown in the lab, that mimic some of the structure and functions of actual organs. The organoids are generated from induced pluripotent stem cells, which can be turned into many different cell types.

“The model of Paneth cells that we developed can facilitate research into how genetic variations, microbes and the intestines’ immune system influence them,” said Robert Barrett, PhD, associate professor of Medicine and Biomedical Sciences and corresponding author of the study. “This knowledge is important because changes in Paneth cells are associated with chronic gastrointestinal disorders such as Crohn’s disease that involve abnormal reactions of the immune system.”

No team of investigators had previously been able to grow intestinal organoids that included functional Paneth cells. By changing the environment in which the organoids were grown, investigators this time were successful. In addition, because organoids derived from induced pluripotent stem cells carry the donor’s genetic material, the new model eventually could lead to personalized treatments for gut illnesses such as inflammatory bowel disease, according to the investigators.

Additional Cedars-Sinai authors include Shachi Patel, Monica Silveira Wagner, Olivia Bay, Christian E. Wong Valencia, Eliska Zgarbova, Cynthia I. Rodriguez, Daniel N. Leal, Michifumi Yamashita, Suzanne Devkota, Kathrin S. Michelsen and Stephan R. Targan.

Funding: Supported by the National Institutes of Health R01 DK123511 (SRT) and the F. Widjaja Inflammatory Bowel Disease Institute. MSW and CWV were supported by the California Institute for Regenerative Medicine (CIRM EDUC4-12751). The study sponsors played no role in the study design collection, analysis, or interpretation of data.

Disclosures: Shachi Patel, Monica Silveira Wagner, Stephan R. Targan and Robert J. Barrett are named as inventors on a U.S. Application No. 19/458,165, each titled “Methodologies to Generate Human Paneth Cells and Enterochromaffin Cells and Determine Their Responses.” The remaining authors disclose no conflicts.

Study Identifies Genetic Drivers of Resistant Hypertension

Cedars-Sinai investigators have identified distinct genetic variants associated with resistant hypertension, a type of high blood pressure that remains uncontrolled despite medication. Their findings, published in the journal Hypertension, suggest potential targets for diagnosing and treating this serious condition.

More than 10% of people with high blood pressure have resistant hypertension, which means they face higher risk of cardiovascular illness and death than people with nonresistant high blood pressure do.

Investigators reviewed genetic data on 92,740 people with consistently high blood pressure in Finland and the United Kingdom. The study identified variants in genes involved in hormonal regulation and blood vessel function that are highly associated with resistant hypertension. The findings highlight overproduction of the hormone aldosterone as a likely cause of difficult-to-control blood pressure.

“Understanding the genetic and bodily pathways that predispose individuals to resistant hypertension may help us identify these patients,” said co-corresponding author Joseph Ebinger, MD, associate professor of Cardiology and director of the Coronary Intensive Care Unit and Clinical Analytics in the Smidt Heart Institute at Cedars-Sinai. “This knowledge can help us develop strategies to lower their blood pressure and reduce their risk for heart attacks and other potentially fatal cardiovascular events.”

Additional Cedars-Sinai authors include Sandy Y. Joung, MSHS, MBA, and Susan Cheng, MD, MPH.

Other authors include Anni Kauko, PhD; Felix Vaura, MD; Paul Hage, BS; Johan Sundström, MD; FinnGen; and Teemu Niiranen, MD.

Funding: This work was funded by the Academy of Finland (321351), the Finnish Foundation for Cardiovascular Research, the Paavo Nurmi Foundation, the Sigrid Juselius Foundation, the Mary and Georg Ehrnrooth Foundation, the Hospital District of Southwest Finland, and the National Institutes of Health grants R01-HL134168, R01-HL131532, R01-HL143227, R01-HL142983, K23-HL153888, K23-HL136853, and R01-HL153382.

New Method Rapidly Analyzes Cell Proteins and Metabolites

Researchers at Cedars-Sinai have developed a fast, new technique for analyzing cells, described in the journal Angewandte Chemie. The approach, called single-injection multi-omics analysis by direct infusion (SMAD), can detect more than 1,300 proteins and more than 9,000 molecular features from a single sample in less than five minutes. The method could help researchers study health, disease and drug responses more quickly and at lower cost, while simplifying analyses that usually require more complex workflows.

To show how the method can be used, the researchers applied it in several case studies. These included tracking how immune cells shift into different inflammatory states and screening how human cells respond to drug treatments.

“By making molecular analysis faster, this approach could one day accelerate drug discovery, enable more powerful machine learning models, and help move rapid, large-scale biological testing closer to clinical use,” said Jesse Meyer, PhD, senior author of the study and an assistant professor of Computational Biomedicine at Cedars-Sinai.

Additional Cedars-Sinai authors include Yuming Jiang, Amanda Momenzadeh and Jesús Muñoz-Estrada.

Other authors include Ivan Salladay-Perez, Utkarsh Tripathi and Anthony J. Covarrubias.

Funding: NIH (R35GM142502, R35GM156893, and R21AG074234).

Cedars-Sinai Health Sciences University is advancing groundbreaking research and educating future leaders in medicine, biomedical sciences and allied health sciences. Learn more about the university.

Ulcerative colitis is a type of inflammatory bowel disease (IBD) that causes chronic inflammation and sores in the colon.

“Ulcerative colitis greatly increases a person’s risk of developing colorectal cancer, but we don’t have a noninvasive way to determine how great each patient’s risk might be,” said Hajar Hazime, PhD, a project scientist in the Abreu Lab at Cedars-Sinai and co-first author of the study. “Undergoing frequent surveillance colonoscopies can help, but preparing for that procedure is especially difficult for someone with ulcerative colitis.”

Additionally, colonoscopy results can be inconclusive, forcing the physician and patient to decide whether to remove all or part of the colon to prevent cancer from developing, Hazime said. Investigators hoped to find a more conclusive and less invasive way to screen these patients.

“Our physician-scientists are continually working to improve cancer screening for our patients,” said Robert Figlin, MD, interim director of Cedars-Sinai Cancer. “We treat more than 60 types of cancer, but our ultimate goal is prevention.”

Each person’s gut is populated with trillions of microbes—bacteria, viruses, fungi and other organisms too small to see with the naked eye. These interact with each other and appear to influence several aspects of a person’s health, including IBD.

Hazime said that these microbes use QSMs to communicate and coordinate their behavior, and that a goal of the study was to determine whether QSMs play a role in causing colon cancer in patients with ulcerative colitis.

When the investigators examined blood samples from human patients with ulcerative colitis and conducted experiments using colon organoids and laboratory mice, they found:

• In the blood of ulcerative colitis patients, there were higher levels of QSMs in patients at higher risk for cancer, who had experienced symptoms for 10 years or longer, than in patients at lower cancer risk, with symptoms for five years or less.
• In colon organoids—tiny clusters of cells that mimic some functions of the human colon—exposure to QSMs caused inflammation, which is a risk factor for tumor development. Because organoids do not contain gut microbes, this showed that elevated QSM levels and the activity of microbes they regulate can increase cancer risk.
• In laboratory mice with a condition that mirrors ulcerative colitis, investigators found higher levels of QSMs in the blood of those that developed tumors than in those that did not. Also, mice exposed to extra levels of QSMs developed more tumors, more quickly, than those not exposed.

“These results show us that quorum sensing molecules are not only associated with colon cancer risk in patients with ulcerative colitis, but that they actually contribute to the formation of these tumors,” said Maria T. Abreu, MD, executive director of the F. Widjaja Inflammatory Bowel Disease Institute and co-corresponding author of the study. “That makes these molecules a potential way to screen patients for cancer risk, but also a possible target for reducing risk.”

Investigators will next focus on pinpointing how QSMs contribute to tumor formation, studying the molecules as a biomarker to predict cancer development, and finding ways to target these molecules to disrupt cancer development, Abreu said.

Additional Cedars-Sinai authors include Irina Fernández, Katerina M. Faust, and Maria A. Quintero.

Other authors include Gregory O’Connor, Juan F. Burgueño, Ana M. Santander, Nivis Brito, Yuguang Ban, Sapna K. Deo, and Sylvia Daunert.

Funding: This work was supported by grants from the National Institute of Diabetes and Digestive and Kidney Diseases (R01DK099076) and the Micky & Madeleine Arison Family Foundation Crohn's & Colitis Discovery Laboratory to MTA as well as from the National Institutes of Health (R01GM127706) and the Department of Defense (W81XWH-20-1-0697) to SD and SKD and the Lucille P. Markey Chair in Biochemistry and Molecular Biology to SD.

Disclosures: MTA is a consultant or on the advisory board of the following companies: AbbVie Inc., Alimentiv Inc., Amgen, Bristol Myers Squibb, Eli Lilly and Company, Genetech, Gilead Sciences, Janssen Pharmaceuticals, Pfizer Pharmaceutical, Takeda Pharmaceuticals, and UCB Pharma.

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The findings, stemming from two complementary studies published in Nature, could lead to therapies to protect the brain in neurological conditions like multiple sclerosis (MS).

Investigators focused on a group of brain cells called “CUX2 neurons.” Located on the outer layer of the brain, known as the cortex, CUX2 neurons are linked to brain communication, movement, thinking and memory. They are also linked to many neurological conditions, including MS, autism, epilepsy and Alzheimer’s disease.

In the first study, researchers found that CUX2 neurons are especially sensitive to damage caused by inflammation. In diseases like MS, the body’s immune system attacks the brain, leading to long-term damage. While MS has been thought to primarily affect white matter in the brain, this research shows that it could also damage particularly vulnerable CUX2 neurons in the gray matter.

This damage may help explain why people with MS can experience memory problems and cognitive decline as the disease progresses.

“The CUX2 neurons are like a ‘canary in the coal mine’ for the brain affected by MS,” said David Rowitch, MD, PhD, co-corresponding author of both studies, deputy director for Research at Guerin Children’s, and professor of Paediatrics at the University of Cambridge. “They are early warning signs of trouble. If we can protect these cells, we might be able to contain the damage before disease progresses.”

To better understand the workings of CUX2 neurons, investigators performed genetic sequencing of brain tissue from people with MS, and in laboratory mice that can model MS. Their study concluded that these neurons, when under stress, sustain much more DNA damage than neighboring brain cells do. Over time, this damage can lead to cell death.

In the second study, investigators found that CUX2 neurons use the molecule ATF4 to help repair their DNA. ATF4 and the molecules it regulates act like a switch that turns on genes that protect critical brain cells from DNA damage.

Even with these repair tools, the study found, CUX2 neurons remain at risk, especially during long-term inflammation. This may be one reason the condition of people with progressive MS continues to worsen even when treatments reduce inflammation.

“We were excited to find that these brain cells already have natural ways to repair themselves,” said Stephen Fancy, PhD, DVM, co-corresponding author of the study and professor in the departments of Neurology and Pediatrics at UCSF. “By uncovering how certain brain cells protect and repair themselves, we have taken a significant step toward developing treatments that could one day preserve brain function and quality of life.”

Through the studies, researchers found that there are several ways to switch on protective processes in the body that can help prevent damage. Further research is needed to bring the findings into clinical use, but they represent a step toward new approaches to treating brain diseases—one that focuses on limiting DNA damage, enhancing repair and bolstering the resilience of critical brain cells.

“Findings from these two studies represent an important milestone in our understanding of neurological disease pathways,” said Nancy Sicotte, MD, chair of the Department of Neurology and director of Multiple Sclerosis and Neuroimmunology at Cedars-Sinai. “This work is a testament to the dedication and innovation of our investigators, who continue to push the boundaries of science and drive discovery in pursuit of effective therapies for patients.”

Other authors who contributed to the first study include: Laura Morcom, Wenlong Xia, Zhaoyang Xu, Yashika Awasthi, Celine Geywitz, Matthew Ellis, Tomas Noli, Amel Zulji, Daniel Yamamoto, Gemma Girdler, Li Kai, Keying Zhu, Mingming Wei, Xiao-Yan Tang, Kimberly Hoi, Julio Gonzalez, Greg Duncan, Adrien Vaquie, Diana Gold, Riki Kawaguchi, Erdong Liu, Yu Sun, Denny Yang, Gregory Jordan, I-ling Lu, Staffan Holmqvist, Theresa Bartels, Katherine Ridley, Jennifer Choi, Santos Franco, Eric Huang, Ben Emery, Daniel Geschwind, Lucas Schirmer, Gabriel Balmus and Brian Popko.

Funding for the first study: This work was supported by funding from the European Research Council (Advanced Grant 789054 to D.H.R.; DecOmPress ERC StG, 950584 to L.S.), the Wellcome Trust (to D.H.R.), NIH (P01 NS083513 to D.H.R. and S.P.J.F.; R01NS128021 and R21NS133891 to S.P.J.F.; R01 NS124166 to S.J.F.; R01NS120981 to B.E.; 1R35NS137478 to B.P.), NIHR Cambridge Biomedical Research Centre (NIHR203312 to D.H.R.), Dr. Miriam and Sheldon G. Adelson Medical Research Foundation (to D.H.R., D.G. and B.P.), the US Department of Defence (MS230141 to S.P.J.F.), Alex’s Lemonade Stand Foundation (to S.P.J.F.), Race to Erase MS (to S.P.J.F.), the National MS Society (RFA-2203-39300 to L.S.; RG-2001-35775 to B.E.), the German Research Foundation (InCheck GRK 2727, Priority Program SPP 2395, NeuroFlame FOR 5705 to L.S.), the UK Dementia Research Institute (to G.B.), Therapeutic Innovation Networks (PNRR-III-C9-2022-I8 to G.B.), the Hertie Foundation (medMS MyLab, P1180016 to L.S.), an endowment from the Warren family (to B.E.), and a gift from the Spangler Foundation (to S.P.J.F.).

Other authors who contributed to the second study include: Wenlong Xia, Laura Morcom, Zhaoyang Xu, I-Ling Lu, Qing Wang, Kimberly Hoi, Mingming Wei, Keying Zhu, Gregory Jordan, Xiao-Yan Tang, Julio Gonzalez, Vanesa Mattera, Sophia Panigrahi, Riki Kawaguchi, Ben Emery, Santos Franco, Daniel Geschwind and Brian Popko.

Funding for the second study: This work was supported by funding from the European Research Council Advanced Grant (789054 to D.H.R.), the Wellcome Trust (to D.H.R), NIH (P01 NS083513 to D.H.R., S.P.J.F; and R35 NS137478 to B.P.) and Dr. Miriam and Sheldon G. Adelson Medical Research Foundation (to D.H.R., D. G, B. P.), and the NIHR Cambridge Biomedical Research Centre (NIHR203312). This work was supported by the NIH NINDS (R01 NS128021 and R21 NS133891 to S.P.J.F.), the U.S. Department of Defence (MS230141 to S.P.J.F.), Alex’s Lemonade Stand Foundation (to S.P.J.F.), Race to Erase MS (to S.P.J.F.), and a generous gift from the Spangler Foundation (to S.P.J.F.).

Cedars-Sinai Health Sciences University is advancing groundbreaking research and educating future leaders in medicine, biomedical sciences and allied health sciences. Learn more about the university.

The findings, published in Science Translational Medicine, could one day improve management of heart failure, in which the heart fails to pump enough blood to meet the body’s need for blood and oxygen. Poor use of oxygen by the heart is an early indicator of heart failure, which affects nearly 7 million people in the U.S.

“Our study shows how MRI could be used to quickly and noninvasively determine heart oxygen use in the clinic,” said Hsin-Jung Yang, PhD, director of Cardiac Imaging Research in the Biomedical Research Imaging Institute and corresponding author of the study. “With further research and development, this advance could unlock new frontiers in early diagnosis, personalized therapy and next-generation treatments for heart failure.”

The current gold standard for measuring heart oxygen use, coronary sinus catheterization, requires threading a thin, flexible tube called a catheter from a patient’s neck or groin into the heart's main vein. The procedure, which takes 30 to 60 minutes and involves injection of a contrast dye to guide the catheter, is too invasive for routine heart oxygen monitoring.

MRI uses radio waves, a strong magnet and a computer to create detailed images of areas inside the body. Standard MRI can only produce clear images of the heart, which moves with every beat and every breath, if patients hold their breath at points during the exam. And in order to use these images to measure oxygen, doctors have to take multiple MRI scans—a process that takes several minutes—and draw blood at the same time.

“The system we designed addresses the motion of the heart,” Yang said. “Patients do not need to hold their breath, and it can give precise numbers within three minutes.”

The team proved the accuracy of its MRI method by using it to measure heart oxygen use in patients with and without heart failure, and comparing its readings to readings obtained by heart catheterization.

“Noninvasive testing that detects issues in the heart’s use of oxygen can provide an early warning that heart failure is developing,” Yang said. “Now that we have promising cardiometabolic therapies lined up, earlier detection may allow us to take steps to prevent and treat the condition.”

David Underhill, PhD, chair of the Department of Biomedical Sciences, said the study makes a major contribution toward improving healthcare for heart disease, the No. 1 cause of death.

“Along with its potential for saving lives through early intervention for heart failure, this accessible tool could offer new avenues for cardiac research,” Underhill said. “It could allow us to study patients who have risk for, but no symptoms of, heart failure without exposing them to catheterization, contrast or radiation.”

Additional Cedars-Sinai authors include Li-Ting Huang, Chia-Chi Yang, Archana Malagi, Xinqi Li, Ghazal Yoosefian, Xinheng Zhang, Ziyang Long, Xiaoming Bi, Janet Wei, Alan C. Kwan, C. Noel Bairey Merz and Debiao Li.

Other authors include Guan Wang, Henghui Zhang, Ranran Zhang, Hao Ho, Yuheng Huang, Michael D. Nelson, Anthony Christodoulou and Rohan Dharmakumar.

Funding: This work was supported by grants from National Institutes of Health (R01HL165211 to H.-J.Y. R01HL181091 to H.-J.Y., R01HL156818 to H.-J.Y., R01HL148788 to R.D., R01HL146158 to C.N.B.M., R01HL124649 to C.N.B.M., R01HL153500 to J.W., K23HL125941 to C.N.B.M., U54AG065141 to C.N.B.M., and U54AG094168-01 to C.N.B.M.), The Barbra Streisand Women’s Cardiovascular Research and Education Program to C.N.B.M., The Linda Joy Pollin Women’s Heart Health Program to C.N.B.M.,The Erika Glazer Women’s Heart Health Project to C.N.B.M., The Adelson Family Foundation to C.N.B.M., and US Department of Defense (HT94252510956 to H.-J.Y.).

Competing interests: C.N.B.M. serves as a director and holds stock in iRhythm. D. Li, A. G. Christodoulou, J. L. Shaw, Y. Xie, and C. Nguyen are inventors on US patent no. 10,436,871 (“Low-rank tensor imaging for multidimensional cardiovascular MRI”). H. J. Yang and C. C. Yang are inventors on a provisional US patent, US Prov 63/721,228 (PCT/US2025/055499, “Systems and methods for determining oxygen consumption using magnetic resonance imaging”). The other authors declare that they have no competing interests.

Cedars-Sinai Health Sciences University is advancing groundbreaking research and educating future leaders in medicine, biomedical sciences and allied health sciences. Learn more about the university.

The conference—Soccer Medicine Updates and New Innovations—is scheduled for Friday, May 22, 2026, at Dignity Health Sports Park in Carson, California. It will be co-hosted by the Department of Orthopaedics and Sports Medicine at Cedars-Sinai and Select Medical, in partnership with Dignity Health. Additional participants include the six-time MLS Cup Champion LA Galaxy, along with fellow FIFA Medical Centres of Excellence partners Duke University and the Hospital for Special Surgery (HSS). 

Cedars-Sinai, Duke University, and HSS represent the only three FIFA Medical Centres of Excellence in the United States, with Cedars-Sinai holding the designation since 2007.

“With the World Cup returning to the United States, this conference reflects our responsibility to share best practices that advance athlete safety and performance on a global stage,” said Bert Mandelbaum, MD, medical director of the Cedars-Sinai FIFA Medical Centre of Excellence, interim chief medical officer of U.S. Soccer and co-chair of the conference. “By bringing together leading experts across disciplines, we aim to translate the latest research and innovation into real-world care for athletes at every level of the game.”

The program will include former and current soccer players and is designed for professional and lay audiences. Programming will explore evidence-based approaches to injury prevention, performance optimization and care for athletes of all levels from youth to adaptive and elite players.

“As the largest provider of outpatient physical therapy and sports medicine in the U.S., we are proud to partner with Cedars-Sinai to co-host this important event showcasing best practices in athlete injury prevention and recovery,” said Alan Evans, vice president of clinical programs and education, Outpatient Rehabilitation Division at Select Medical. “When clinicians, athletic trainers and performance specialists collaborate, we raise the standard of care and help athletes stay healthy, compete at their highest level and return to play safely. Together, we are advancing the future of sports medicine and strengthening the world’s athletic community.”

"We are honored to be part of this collaborative effort to advance athlete care and innovation during this exciting time for Los Angeles," said Julie Sprengel, California president of Dignity Health, a member of CommonSpirit Health. "This educational conference at the Dignity Health Sports Park embodies the shared commitment to excellence that Dignity Health has with Cedars-Sinai and Select Medical."

Advancing Innovation and Collaboration in Athlete Care

The FIFA World Cup is one of the largest sporting events in the world, with 48 teams set to compete across the United States, Canada and Mexico in 2026. Preparing athletes for competition at this scale requires coordinated, multidisciplinary care that spans emergency preparedness, injury management and return-to-play decision-making.

The conference will be in person and feature a dynamic format with internationally recognized faculty who specialize in all aspects of soccer. Programming will include interactive sessions, panel discussions and on-demand educational content, with continuing education credits available.

Sessions will focus on medical and performance challenges, including:

• Emergency action planning for sudden cardiac arrest and cardiac considerations for return to play
• Advances in concussion management and evolving safety regulations
• Mental health considerations
• Knee injury evaluation, treatment and evidence-based return-to-play guidelines
• Common soft tissue injuries and strategies that bridge performance and injury prevention
• Innovations in athlete care, including biologics, youth athlete considerations and burnout prevention
• Team-based, interprofessional approaches to athlete care

The conference Scientific Planning Committee is co-chaired by Mandelbaum and Josh Scott, MD, a nationally recognized sports medicine physician and venue medical director for World Cup 2026 in Los Angeles.

For more information about the conference and to register, click here.

Cedars-Sinai Health Sciences University is advancing groundbreaking research and educating future leaders in medicine, biomedical sciences and allied health sciences. Learn more about the university.

The discovery, published in Cell, has important implications for understanding how a wide variety of intestinal disorders may develop.

“Our research opens the door to treatments that focus on restoring key molecular signals in vulnerable regions of the colon,” said Ophir Klein, MD, PhD, executive director of Cedars-Sinai Guerin Children’s, executive vice dean of Children’s Health, and the David and Meredith Kaplan Distinguished Chair in Children’s Health. Klein is the senior author of the study.

Prior research has shown that the four sections of the colon—ascending, transverse, descending and sigmoid—have different functions and risks for disease, but it wasn’t clear why these variations exist.

In this study, the investigators showed that the identity of distinct regions of the colon are regulated by the gut microbiome. They identified nicotinic acid, a molecule produced by certain bacteria in the gut microbiome, as a main driver of these regional differences in the colon’s sections. Nicotinic acid, also known as niacin, part of the vitamin B3 family, helps the body convert food into energy and supports the health of cells.

The researchers compared laboratory mice with and without a microbiome. They found that production of nicotinic acid by bacteria in the upper colon activates a protective mechanism in colon cells. In mice without a microbiome, minimal nicotinic acid was produced, and cells in the upper colon became more vulnerable to damage and disease.

Investigators also studied human colon tissue samples. They found that the different sections of the human colon showed regional characteristics similar to patterns observed in mice. And in samples from human patients with Crohn’s disease— a type of bowel disease in which abnormal immune system activity causes inflammation—this protective mechanism was reduced.

“Our work highlights the importance of studying host microbiome interactions with careful attention to specific colon regions, rather than treating the colon as a uniform organ,” said Jeremie Rispal, PhD, a postdoctoral scholar at the University of California, San Francisco, and the first author of the study. “We learned that the microbiome controls regional differences and tissue protection.”

Further study will be needed to confirm the precise mechanisms behind this protective effect and to determine how these findings might be used in new therapies for intestinal disorders.

Additional Cedars-Sinai authors include Manasa Vegesna, Dedeepya Vaka, and Dario Boffelli .

Other authors include Jasmine R. Garcia, Brisa Palikuqi, Seung Woo Kang, Coralie Trentesaux, Juan Du, Nicola R. Realini, Paige N. Spencer, James M. Gardner, Annika Hausmann, Michael G. Kattah, and Ken S. Lau.

Funding: This work was funded by NIH U01DK103147 from the Intestinal Stem Cell Consortium (to O.D.K. and D.B.), RC2-DK140862 (to O.D.K. and D.B.), R01DK103831 (to K.S.L.), F31DK127687 (to P.N.S.), T32HD007502 (in support of P.N.S.), T32CA119925 (in support of S.K.), the Leona M. and Harry B. Helmsley Charitable Trust G-1903-03793 (to the VUMC Gut Cell Atlas of which K.S.L. is a member), the Stanley Cohen Innovation Fund (to K.S.L.), the Benioff Center for Microbiome Medicine (to J.R.), and the PZ00P3_223765 SNSF Ambizione grant (to A.H.). Organoid work was supported by funding from the Kenneth Rainin Foundation and NIH R01 DK14167. The Kattah Lab has received research support from Eli Lilly. J.R. was supported by the Bakar Aging Research Institute postdoctoral fellowship and the Bettencourt Schueller foundation.

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Throughout her career, Cheng has maintained National Institutes of Health funding for research aimed at uncovering the drivers of cardiovascular aging. She has authored more than 450 scientific studies, many appearing in high-impact journals, including JAMA, Circulation and The New England Journal of Medicine.

Cheng identified differences in how males and females develop elevated blood pressure and demonstrated how people vary in their responses to COVID-19 vaccines over time. Her research has garnered multiple awards and contributed to Cedars-Sinai’s reputation as an international leader in biomedical sciences.

“Dr. Cheng is the perfect leader to build and enrich our already flourishing Department of Cardiology,” said Shlomo Melmed, MB, ChB, dean of the Medical Faculty and executive vice president of Medicine and Health Sciences. “We welcome her to this academic leadership role and look forward to the contributions she will make in strengthening the Smidt Heart Institute.”

Cheng, who succeeds Christine M. Albert, MD, MPH, has served on the editorial boards of major professional journals and on leadership committees for the American Society for Clinical Investigation, the American Heart Association and the American College of Cardiology.

She founded the largest COVID-19 clinical research program on the West Coast at the outset of the pandemic in 2020. More recently, she has led research to investigate the public health effects of the 2025 Los Angeles wildfires.

Cheng has mentored dozens of junior faculty members in cardiology, anesthesiology, neurology, obstetrics and oncology, taking special pride in advising early-career investigators as well as high school and college students.

“I look forward to supporting the Smidt Heart Institute’s talented clinicians and researchers as they work to improve the lives of those affected by cardiovascular disease,” Cheng said.  

Cheng received her bachelor’s degree from Harvard College and her medical degree from McMaster University in Canada, as well as a master of medical science degree from the Massachusetts Institute of Technology and a master of public health degree from Harvard University. She completed her internal medicine training at Johns Hopkins University and cardiology training at Brigham and Women’s Hospital, where she served as associate director of the Cardiovascular Imaging Core Laboratory.

In her new role, Cheng will lead strategic clinical, research and educational growth for the Department of Cardiology. As the new department chair, she will hold the Stephen R. Corday, MD, Distinguished Chair in Cardiology.

“Dr. Cheng has strengthened our institution and made many meaningful contributions through her research laboratory since joining Cedars-Sinai seven years ago,” said Eduardo Marbán, MD, PhD, executive director of the Smidt Heart Institute and the Mark Siegel Family Foundation Distinguished Chair. “We are excited for her to continue developing our world-class cardiology department.”

Read more from the Cedars-Sinai Newsroom: Cedars-Sinai Reports Heart Attacks, General Illness Spiked After LA Fires

Revealing How Transplanted Neural Stem Cells Preserve Vision

Cedars-Sinai investigators working to optimize a cell-based treatment for retinitis pigmentosa have uncovered how transplanted neural stem cells interact with host retinal cells to preserve vision. The findings, published in Nature Communications, may guide future research toward strategies to treat degenerative eye disease.

“We used single-cell analysis to show that neural stem cells can protect vision in several ways, including providing protective proteins, restoring retinal cells to a healthier state, reducing cellular stress, and maintaining retinal integrity,” said Clive Svendsen, PhD, executive director of the Board of Governors Regenerative Medicine Institute and co-corresponding author of the study.

Investigators transplanted neural stem cells into the retinas—the light-sensitive tissue lining the back of the eye—of laboratory rats with retinal degeneration. Previous studies have shown the transplants significantly reduced vision loss in the animals for up to 180 days, the equivalent of about 20 years in humans. In this study the team examined interactions between the transplanted cells and diseased retinal cells to better understand the neural stem cells’ protective effects.

“Our study reveals that the interaction between neural stem cells and host retinal cells dynamically changes over time,” said Shaomei Wang, MD, PhD, professor of Biomedical Sciences and co-corresponding author of the study.  “Through a better understanding of this process, we may be able to develop more powerful approaches to treat eye diseases in the future.”

Investigators are now evaluating the use of neural stem cells engineered to express key protective proteins identified in this study to further improve the host retinal environment. 

Additional Cedars-Sinai authors include Saba Shahin, Shaughn Bell, Bin Lu, Hui Xu, Jason Chetsawang, Stephany Ramirez, Jorge S. Alfaro, Alexander Laperle and Soshana Svendsen.

Other authors include Somanshu Banerjee and Vivek Swarup.

Funding: This work was supported by the California Institute Regenerative Medicine (LSP1-08235). J.C. was supported by CIRM-EDUC-08383 and S.R. was supported by CIRM-EDUC2-12638, and funding from the Board of Governors Regenerative Medicine Institute at Cedars-Sinai Medical Center.

Preclinical Study: Protein Regulates Autoimmune Response

Cedars-Sinai Health Sciences University investigators have identified for the first time a protein’s role as a “dimmer switch” that can calm an overactive immune system and restrain harmful inflammation. The protein, Butyrophilin 2A2 (BTN2A2), interacts with a key molecule that controls the strength of T-cell responses.

The findings, published in Nature Communications, define a unique pathway that helps balance immune activity and could be harnessed to limit damage caused by a variety of autoimmune diseases.

In laboratory mice, loss of BTN2A2 led to exaggerated immune reactions and an increase in damaging kidney inflammation called glomerulonephritis. Treatment with BTN2A2 reduced disease severity by increasing immune-regulating T cells and lowering inflammation.

Supporting laboratory experiments in human T-cells demonstrated similar immune-calming effects.

“Glomerulonephritis remains a leading cause of chronic kidney disease and kidney failure worldwide, with limited treatment options,” said Ananth Karumanchi, MD, co-corresponding author of the study and director of the Renovascular Research Center at Cedars-Sinai. “Our findings provide a strong foundation for future studies aimed at modifying immune-driven kidney disease rather than simply managing its symptoms. The pathway could also be targeted in a range of autoimmune and inflammatory diseases including rheumatoid arthritis, multiple sclerosis, inflammatory bowel disease, and transplant rejections.”

Other Cedars-Sinai authors include Shafat Ali, Anders H. Berg, Michifumi Yamashita, Ambart E. Covarrubias, Jordan Mundell, Pranali N. Shah, Ruan Zhang, Vincent Dupont, Bong-Ha Shin, Shen Yang, Madhusudhanarao Katiki, Ramachandran Murali, Margareta D. Pisarska, Ravi Thadhani, Peter S. Heeger and Stanley C. Jordan

Pinpointing Indicators of Cancer Wasting Syndrome

An analysis of biomarkers in patient blood samples by Cedars-Sinai Health Sciences University investigators could help with early detection of cachexia, or cancer wasting syndrome.

The study, published in Cancers, explores biologic signals detectable in the blood that could be used to design future strategies for assessing patient risk and develop therapies aimed at mitigating fatigue and muscle and fat loss experienced by many patients with cancer.

“We found that in patients with advanced non-small cell lung cancer, cachexia biomarkers change over time,” said Kamya Sankar, MD, co-medical director of the Thoracic Disease Research Group at Cedars-Sinai Cancer and corresponding author of the study. “And treatments targeting one of the early cachexia biomarkers we identified, an inflammatory protein called GDF-15, are already under evaluation in clinical trials.”

Investigators measured the blood of 27 patients with non-small cell lung cancer at two different time points. In patients with early cachexia, they found higher levels of inflammatory proteins such as GDF-15. In patients with later-stage cachexia, they found increased mitochondrial DNA, which comes from the parts of cells that convert food into energy.

Larger, prospective studies are required to validate the clinical benefit of these biomarkers, but they could serve as the basis for risk assessment of patients and may inform design of future clinical trials of therapies for cancer-associated cachexia, Sankar said.

Additional Cedars-Sinai authors include Elham Kazemian, Nicole Lorona, Carlos D. Cruz-Hernández, Mitra Mastali, Akil A. Merchant, Jennifer Van Eyk, Karen L. Reckamp, Neil A. Bhowmick, and Jane C. Figueiredo.

Other authors include Alex K. Bryant and Puneeth Iyengar. 

Funding: This work was supported by the U.S. National Cancer Institute (U54CA260591, PI Figueiredo), Department of Defense (LC240075, PI Sankar), and Cedars-Sinai CTSI grant (UL1TR001881, PI Sankar).

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“These rising cancer rates are expected worldwide, and large-scale efforts need to be made to encourage lifestyle changes and develop screening programs to reduce them,” said Ju Dong Yang, MD, medical director of the Liver Cancer Program and professor of Medicine at Cedars-Sinai and co-corresponding author of the study.

Liver Cancer

Yang said that up to 70% of liver cancers could be prevented through lifestyle changes, because while hepatitis B and C were once leading causes of liver cancer in the U.S., they are being eclipsed.

“Metabolic dysfunction-associated steatotic liver disease, or MASLD, is emerging as a leading cause of liver cancer in Western countries, including the U.S.,” Yang said. “This is a buildup of fat in the liver that is associated with diabetes, obesity, and uncontrolled high cholesterol and high blood pressure.”

Taking steps to help control these risk factors is the best way to reduce risk, Yang said.

Yang said that only about 20% of people in the U.S. with cirrhosis from hepatitis and other chronic liver conditions receive liver cancer screening, which could help improve early detection and patient outcomes. Only about 30% of liver cancers are detected at an early enough stage for cure, Yang said.

Esophageal and Gastric Cancers

Lifestyle factors and limited screening also come into play in risk for esophageal and gastric cancers, said Alexandra Gangi, MD, director of the Division of Surgical Oncology in the Jim and Eleanor Randall Department of Surgery and director of the Gastrointestinal Tumor Program.

“These tumors cause few symptoms before the cancer has spread—and they tend to spread rapidly,” Gangi said. “To reduce risk, focus on preventable issues such as obesity, tobacco and alcohol use, and diet. And if you have other risk factors such as chronic acid reflux, gastritis or family history of these cancers, speak with your doctor about screening.”

Colorectal Cancer

Everyone should be screened for colorectal cancer by age 45—but those with a family history of the disease should begin sooner, said Alessio Pigazzi, MD, PhD, director of the Division of Colorectal Surgery. Results of that first screening, along with other risk factors, will help determine how often follow-up screenings are needed.

“Late diagnosis makes colorectal cancer highly lethal, while early diagnosis leads to very high cure rates,” Pigazzi said. “To reduce risk, everyone should eat a diet focused on whole foods that are high in fiber and low in sugars and animal fats, exercise regularly, keep up with screenings, and watch for colon cancer symptoms such as frequent rectal bleeding or unexplained changes in bowel habits.”

Pancreatic Cancer

Pancreatic cancer is another GI cancer usually diagnosed in advanced stages—with 50% of people diagnosed when the disease has already spread, said Arsen Osipov, MD, medical director of Pancreatic Cancer and Multidisciplinary Programs and Integration.

“There have been recent advances in early detection and treatment, including blood-based ‘liquid biopsy’ tests and structured screening programs for those with strong genetic risk,” Osipov said. “And multidisciplinary clinics, such as one pioneered at Cedars-Sinai, help accelerate diagnosis and treatment planning, and improve access to clinical trials and patient outcomes.”

To reduce pancreatic cancer risk, Osipov recommended paying attention to modifiable lifestyle factors similar to those for other GI cancers. He also suggested that people with chronic pancreatitis or family history of pancreatic cancer consider genetic counseling and participation in a high-risk surveillance program.

On the Horizon

Cedars-Sinai research is changing the landscape of GI cancer detection and treatment, said Katelyn Atkins, MD, PhD, interim chair and medical director of Radiation Oncology. Blood-based biomarkers such as circulating tumor DNA are improving early detection and allowing for tailored treatments and better detection of recurrence in colorectal cancer—and are now being leveraged for other GI sites, Atkins said.

“Improvements in radiation oncology techniques are allowing us to deliver the therapy more precisely and better protect nearby organs, making it safer to deliver more intense and effective treatment,” Atkins said. “There is also growing use of radiotherapy as an alternative to radical surgery in rectal, esophageal and gastroesophageal cancers.” 

Biomarker-driven treatment is also improving integration of radiotherapy into treatment regimens that also include surgery, chemotherapy and immunotherapy.  

“This shift toward more personalized, biology-driven treatment approaches helps us extend survival and preserve quality of life for patients with GI cancers,” said Robert Figlin, MD, interim director of Cedars-Sinai Cancer. “We will continue to work to improve treatment options and prevent cancer incidence in our community.”  

Cedars-Sinai Health Sciences University is advancing groundbreaking research and educating future leaders in medicine, biomedical sciences and allied health sciences. Learn more about the university.

If validated in further studies, the artificial intelligence-based platform could be used to improve treatment selection in virtually any cancer type. Results from a study of the platform’s effectiveness are published in the Journal of Clinical Oncology.

“Currently, we have no conclusive data to show which of the two approved chemotherapy regimens for patients with advanced pancreatic cancer is more effective,” said Andrew Hendifar, MD, medical director of Pancreatic Cancer at Cedars-Sinai Cancer and first author of the study. “So we start with one, do our best to quickly gauge the patient’s response, and switch if needed.”

The problem with this, Hendifar said, is that putting an ill patient on a chemotherapy regimen that isn’t working worsens their health rather than improving it. Biomarkers from blood or tissue can help predict treatment response and guide these decisions in other cancer types, but currently, no biomarkers exist for pancreatic cancer.

“This endeavor is an example of applying AI technology to an unmet clinical need, and offers tremendous translational potential,” said Robert Figlin, MD, interim director of Cedars-Sinai Cancer. “It aligns perfectly with our goal of personalizing cancer treatment for our patients and improving outcomes for all.”

To develop the tool, investigators used a platform called Computational Histology Artificial Intelligence, or CHAI. CHAI analyzes images of microscope slides containing samples of tumor tissue, which are stained to highlight minute details of the cells. Almost all patients have these samples taken when their tumors are biopsied.

The team analyzed tissue characteristics in samples from 25,000 pancreatic cancer patients who had received one chemotherapy regimen or the other. The platform’s AI capabilities made it possible to analyze more than 30,000 different features of the tissue samples. Investigators then matched tissue characteristics to treatment response to create the predictive tool.

When they tested the tool on data from a large clinical trial using the two pancreatic cancer treatment regimens, they found that it was able to accurately predict each patient’s response to the treatment received.

“Unlike most biomarker tests, where you need an extra sample of tissue or blood, this test requires only a scanned image of the patient’s existing biopsy slide,” Hendifar said. “You just send the image electronically and quickly receive a result with the treatment preference. And you don’t just learn which treatment is preferred. You learn how much more effective it is likely to be.”

The tool needs to be further validated in patients undergoing treatment before it is ready for clinical use, but Hendifar said that with that validation it could eventually be applied to other solid tumor types. It could even compare the potential benefit of different types of therapy, such as radiation therapy versus surgery.

“If the chance that a particular treatment will benefit a patient is 50-50, which is quite common in cancer therapy, then this may serve as a powerful tool to aid physician and patient decision-making,” Hendifar said. “And we can train the digital tool not just to choose between two available treatments, but to choose between multiple available treatments.”

Additional Cedars-Sinai authors include Brent K. Larson, DO; Vladimir Kazarov, MS; Natalie Moshayedi, BS; and Arsen Osipov, MD.

Other authors include Viswesh Krishna, BS; Vrishab Krishna, BS; Haochen Zhang, PhD; Katelyn Smith, BA; Kawther Abdilleh, PhD; Snehal Sonawane, MD; Akshay Neema, MS; Asit Tarsode, MS; Ekin Tiu, MS; Vivek Nimgaonkar, MD; Shawn Hutchinson, MSc; Daniela Bevacqua, BS; Sudheer Doss, PhD; Alejandra Alvarez, MS; Drew Watson, PhD, MBA; Waleed M. Abuzeid, MD; Barbara T. Grunwald, MD; Marcus Noel, MD; Rashmi Samdani, MD; Dove Keith, PhD; Rosalie C. Sears, PhD; Davendra Sohal, MD, MPH; Christos Fountzilas, MD; Grainne M. O’Kane, MD; Robert C. Grant, MD, PhD; Eric A. Collisson, MD; Lesli A. Kiedrowski, MS, MPH; Trevor J. Royce, MD, MS, MPH; Anirudh R. Joshi, MS; Aatur D. Singhi, MD, PhD; and Jennifer J. Knox, MD, MSc.

Funding: Supported in part by the Pancreatic Cancer Action Network (PanCAN - Know Your Tumor), the University Health Network, Toronto (COMPASS trial), and Valar Labs, Inc.

Cedars-Sinai Health Sciences University is advancing groundbreaking research and educating future leaders in medicine, biomedical sciences and allied health sciences. Learn more about the university.

“Too often, when a young woman has heart disease symptoms, a physician will ignore those symptoms and tell her that she needs to lose weight,” said Bairey Merz, director of the Barbra Streisand Women’s Heart Center in the Smidt Heart Institute at Cedars-Sinai. “That’s because heart disease symptoms in women can be very different from what men experience. So it’s crucial that women know what to look for.”

Although heart disease is the leading cause of death among women in the U.S., according to the Centers for Disease Control and Prevention, most heart disease research has been conducted on men. And even though rates of heart disease and heart attacks are increasing among women 35 to 54 years old, they are less likely to receive evidence-based treatments such as statins and more likely to be told they are “too young” to have heart disease, Bairey Merz said.

“These delays and dismissals have had serious consequences,” she said. “The Women’s Ischemia Syndrome Evaluation [WISE] study that I led for the National Heart, Lung, and Blood Institute helped us better understand that heart disease doesn’t always look the same in women. That insight ultimately pushed the field to rethink and improve how we diagnose and treat it.”

Despite these advances, women with heart disease are still more likely to be misdiagnosed, underdiagnosed or undertreated—sometimes delaying care that could save their lives.

“The good news is that heart disease is largely preventable,” Bairey Merz said. “And for women in particular—who may not experience obvious symptoms or whose symptoms are subtle—knowledge is a powerful prevention tool.”

To explain what women should watch for, the Cedars-Sinai Newsroom spoke with Bairey Merz about what women can do to protect their hearts and advocate for the healthcare they need.

What are some of the biggest myths about heart disease?

Many people believe that heart disease primarily affects men, that heart attacks always involve crushing chest pain, or that cancer is the top cause of death. In reality, heart disease kills more women than all cancers combined, yet fewer than half of women recognize it as their greatest health threat.

While men tend to develop cardiovascular disease earlier, women are more likely to experience poorer outcomes.

Why are heart attack rates increasing among younger women?

For decades, heart attack death rates declined sharply, thanks to improved research, standardized treatment guidelines, and widespread use of effective medications and procedures. While heart attack deaths are still much lower than they once were, the increase in heart problems among younger adults is concerning.

Researchers are looking into exact causes for the increase, but we know that contributing factors include low levels of physical activity and prolonged sedentary behavior, rising rates of diabetes and obesity, chronic stress, and environmental exposures such as air pollution.

What does a heart attack feel like for women?

The so-called “Hollywood heart attack”—tingling in the left arm that leads to sudden, crushing chest pain—is common in men and can occur in women as well. But many women experience subtler symptoms, including shortness of breath, nausea, unusual fatigue, back or jaw pain, or chest discomfort that doesn’t feel severe or dramatic.

Because these symptoms don’t match common expectations of a heart attack, they may be overlooked or dismissed. Anyone experiencing them should seek medical care immediately.

What causes heart attacks in women?

An increasing number of heart attacks are occurring in people without significant blockages in the major coronary arteries, a pattern seen more often in women. While men’s heart disease more commonly involves blockage in large arteries, women are more likely to experience dysfunction of the heart’s smaller blood vessels. This condition—called ischemia with no obstructive coronary artery disease [INOCA]—can cause reduced blood flow to the heart even when major arteries appear clear.

Even women who are physically fit can develop INOCA. In the past, if a woman had heart attack symptoms but a “normal” angiogram showing clear major arteries, her condition might not have been recognized. Continued awareness and ongoing education around INOCA are helping clinicians better diagnose and treat these patients.

What is a normal heart rate for women?

A normal resting heart rate for most adults is between 60 and 100 beats per minute, according to the American Heart Association. Because women’s hearts are typically smaller, their resting heart rate may run slightly higher than men’s. Women should consult their doctor if their resting heart rate is below 60 or above 100 beats per minute when not exercising.

How can women protect heart health and prevent heart disease?

Heart disease develops silently over decades. While heart disease can be managed with highly effective treatments, prevention is the most powerful strategy.

An estimated 80% of heart disease cases are preventable with lifestyle modifications. These include staying current with annual screenings and knowing cholesterol, blood pressure and blood sugar levels; exercising at least 30 minutes daily; breaking up prolonged sitting because a sedentary lifestyle is considered as strong a risk factor as smoking; managing stress; getting seven to nine hours of sleep; avoiding smoking; and following a nutritious diet.

A Mediterranean-style, largely plant-based diet rich in fruits, vegetables, nuts, beans, whole grains, olive oil and lean proteins is recommended. Parents are encouraged to help ensure their children make healthy food choices, too.

Heart health isn’t about deprivation. It’s about building lifelong habits that prevent disease before it starts.

Read more on the Cedars-Sinai Blog: High Blood Pressure—What Women Need to Know

This condition not only can accelerate cognitive decline but is often mistaken for an underlying neurological condition—delaying proper diagnosis and treatment.

In a recent review published in the journal Alzheimer’s & Dementia, Cedars-Sinai researchers explored how UTI-induced delirium affects brain function, why individuals with dementia are especially vulnerable, and the critical need for early recognition and intervention.

“It’s a vicious cycle where dementia increases the risk of infection, and infection-related delirium accelerates cognitive decline,” said Shouri Lahiri, MD, principal investigator of the Critical Care Neurodegenerative Medicine Lab, director of the Neurosciences Critical Care Unit and Neurocritical Care Research at Cedars-Sinai, and senior author of the review.

Previous laboratory studies by Lahiri and his colleagues revealed that the immune system’s response to UTI-induced delirium—specifically the inflammatory protein interleukin-6—can cause changes in the brain. Blocking this pathway reversed delirium-like symptoms in mice.

Lahiri sat down with the Cedars-Sinai Newsroom to discuss UTIs as a potentially preventable and treatable contributor to cognitive decline and the importance of early recognition and swift treatment.

What is delirium, and how is it different from memory loss?

Delirium is a sudden change in thinking and awareness. It affects attention, judgment and short-term memory, and develops over hours or days.

Memory loss from conditions such as Alzheimer’s disease progresses slowly over time. Delirium, by contrast, is acute and usually triggered by a medical illness, such as a urinary tract infection, dehydration or infection elsewhere in the body.

Why can urinary tract infections cause confusion, especially in older adults?

Our research shows UTIs can cause acute brain dysfunction through inflammation. An infection in the bladder releases inflammatory signals into the bloodstream, which can affect the brain and disrupt normal function, leading to delirium.

Older adults are more vulnerable because their brains are often less resilient to physiological stress.

UTIs aren’t the only infections that can trigger this response. Any systemic infection, including pneumonia, gastrointestinal infections or skin infections, can provoke widespread inflammation that affects the brain and causes acute confusion.

Why are people with Alzheimer’s disease at higher risk for UTIs?

People with Alzheimer’s may have challenges upkeeping with hygiene and age-related hormonal changes that increase UTI risk. Alzheimer’s can also impair sensation and communication, making it harder for patients to recognize or report well-known UTI symptoms such as burning or urgency to urinate. As a result, infections may go untreated until they trigger delirium.

For people without dementia, delirium increases the risk of developing dementia by about threefold. Repeated episodes further raise that risk.

Why can a UTI make Alzheimer’s symptoms suddenly worse?

A UTI can cause a rapid cognitive decline that looks like a sudden worsening of Alzheimer’s disease. The key difference is timing. Alzheimer’s progresses gradually, while delirium causes an abrupt change from a person’s baseline.

We believe inflammation related to infection places added stress on an already vulnerable brain, which can worsen dementia symptoms and, in some cases, cause lasting damage.

Is delirium from a UTI reversible?

Early treatment offers the best chance for recovery. When UTIs are identified and quickly treated, delirium symptoms can improve or resolve. However, in some cases, cognitive effects can persist or become permanent. That’s why early recognition is critical.

Because UTIs don’t always cause obvious urinary symptoms, especially in older adults, we need to change the way we diagnose UTIs, using a mix of clinical observations and urinary and blood tests that show infection, to recognize when a UTI is behind sudden confusion.

How can caregivers tell the difference between Alzheimer’s progression and a UTI?

Sudden change is the biggest warning sign. Dementia generally does not cause abrupt declines. If someone with Alzheimer’s suddenly becomes much more confused, less alert or behaves very differently, that may signal delirium.

Other changes to look out for include changes in urination patterns, incontinence, pain, or changes in urine color or odor.

What can caregivers do to help prevent UTIs and delirium?

Caregivers should make sure the person they’re taking care of maintains good hygiene and adequate hydration. Caregivers should also notify a physician if UTIs are recurrent, because treatments are available to reduce repeated episodes.

Also, being aware of sudden changes in mental status and seeking prompt medical care can make a significant difference.

Are UTIs linked to delirium in other neurological conditions?

Yes. Parkinson’s disease is a key example. Many people with Parkinson’s have difficulty fully emptying their bladder, which increases infection risk. UTIs can worsen Parkinson’s movement symptoms, just as they worsen cognition in Alzheimer’s disease.

What is your lab studying next?

We are studying new drugs that target inflammatory pathways involved in UTI-related brain dysfunction, with the goal of advancing them to clinical trials. We are also developing diagnostic approaches to better identify UTIs in patients who  don’t have the well-known urinary symptoms.

Cedars-Sinai Health Sciences University is advancing groundbreaking research and educating future leaders in medicine, biomedical sciences and allied health sciences. Learn more about the university.

The new, five-year grant to examine sex-based differences in multiple age-related diseases supports the Microvascular Aging Effects—Women’s Evaluation of Systemic Aging Tenacity in Heart, Brain and Frailty study, commonly called MAE-WEST HBF. The acronym is a nod to the late actor, who reportedly once said, “You’re never too old to become younger.”

MAE-WEST HBF is funded as a Specialized Center of Research Excellence (SCORE) on Sex Differences through the NIH Office of Research on Women’s Health. It builds on prior research from Cedars-Sinai’s Barbra Streisand Women’s Heart Center that showed small blood vessel disease, chronic inflammation and iron buildup in women are linked to impaired heart, brain and kidney function, and declining physical strength.

“Armed with this funding, we are eager to continue uncovering biological mechanisms behind sex-based differences in aging and heart health,” said C. Noel Bairey Merz, MD, the principal investigator of MAE-WEST HBF and director of the Barbra Streisand Women’s Heart Center in the Smidt Heart Institute. “A better understanding of the causes of common age-related conditions in women could lead to more effective prevention and treatment strategies.”

For more than two decades, Bairey Merz and her team have made landmark discoveries in women’s heart health, particularly in coronary microvascular disease—a condition that occurs more often in women and results from damage to the heart’s smallest blood vessels. Symptoms of the condition, which can be subtle, were previously often dismissed, misdiagnosed or undertreated. But improved diagnostic tools and treatments resulting from Bairey Merz’s discoveries have contributed to significant reductions in cardiovascular deaths among women.

The new study brings together a multidisciplinary team of experts, including Pascal Sati, PhD, director of the Neuroimaging Program in the Department of Neurology at Cedars-Sinai. Collaborators at UCLA will oversee biostatistical analysis, while those at the University of Texas at Arlington will lead frailty research.

“We now have effective treatments for small vessel dysfunction in the heart,” Bairey Merz said. “If we can better understand its effects on the brain and musculoskeletal system, we may be able to find ways to prevent or slow multiple age-related diseases—including declines in cognition and mobility—in both women and men.”

Although women generally live longer than men do, women experience higher rates of chronic conditions and so spend more years in poor health. Ultimately, investigators hope the new study will pave the way for a future in which healthy aging for women includes earlier screenings, advanced technology, and preventive care that identifies risks and stops diseases before they begin.

“After more than 25 years of progress in women’s cardiovascular research, this grant helps advance whole-person care that supports heart health, brain function and physical strength,” said Eduardo Marbán, MD, PhD, executive director of the Smidt Heart Institute. “All three are equally essential to healthy aging.”

Cedars-Sinai Health Sciences University is advancing groundbreaking research and educating future leaders in medicine, biomedical sciences and allied health sciences. Learn more about the university.

“This new academic alliance between these premier Los Angeles institutions will advance scientific and academic achievements for the broader Los Angeles community and beyond,” said Peter L. Slavin, MD, president and CEO of Cedars-Sinai Medical Center and Cedars-Sinai Health System.

The partnership features joint translational discovery grants, as well as co-hosted symposia, shared training opportunities, and joint student and faculty appointments.

“Our partnership with Cedars-Sinai provides an important new pathway to clinical impact,” said Caltech Provost David A. Tirrell, PhD, the Ross McCollum-William H. Corcoran Professor of Chemistry and Chemical Engineering and the Carl and Shirley Larson Provostial Chair.

Shlomo Melmed, MB, ChB, executive vice president of Medicine and Health Sciences and dean of the Medical Faculty at Cedars-Sinai, said the goal of the partnership is to reshape patient care and biological understanding, together.

“Recognizing the unique strengths of each institution, we feel confident this partnership will benefit the greater field of science,” Melmed said.

Cedars-Sinai Health Sciences University combines a robust basic, translational and clinical sciences enterprise with a large and diverse patient population, along with an expanding biospecimen repository. Caltech brings exceptional expertise in engineering, computational modeling, chemistry, and quantitative biosciences, along with advanced research in molecular, cellular and systems biology.

“Better healthcare for all requires bold innovation. This partnership brings together Cedars-Sinai’s clinical leadership and Caltech’s scientific excellence to deliver it,” said  Viviana Gradinaru, PhD, the Lois and Victor Troendle Professor of Neuroscience and Biological Engineering, Howard Hughes Medical Institute Investigator, and director and Allen V. C. Davis and Lenabelle Davis Leadership Chair of the Merkin Institute for Translational Research.

The official partnership has been years in the making, with investigators like Ueli Rutishauser, PhD, director of the Center for Neural Science and Medicine and professor of Neurosurgery, Neurology and Biomedical Sciences at Cedars-Sinai, holding faculty appointments at both institutions. Those joint faculty positions opened the door for thoughtful discussions on how the two entities could increase their collaborations.

Ophir Klein, MD, PhD, executive director of Cedars-Sinai Guerin Children’s, executive vice dean of Children’s Health and the David and Meredith Kaplan Distinguished Chair in Children’s Health, recognized the potential synergy when he joined Cedars-Sinai in 2022.  Klein then initiated co-hosted programs to foster greater collaboration.

The first joint symposium, in 2024, concentrated on developmental and stem cell biology. The second, in 2025, focused on computational and experimental neuroscience. Both events sparked enthusiasm and spurred the impetus for further collaborations.

“The opportunity to engage regularly through these events will lead to a more profound partnership between the two institutions and deeper connections among faculty and trainees,” Klein said. “There’s a unique energy in the room when two complementary forces have a shared desire for the best in science and accelerated application.”

Another element of the strengthened partnership involves a pilot grant program to catalyze research that unites clinical insight, engineering and fundamental biological discovery.

The joint grant program will award up to four recipients with support for a one-year project and an opportunity for a second year. Funds will be split between investigators at Cedars-Sinai and Caltech.

“We are eager to stimulate interdisciplinary collaborations that support research and integrate biomedical, clinical, computational and engineering approaches,” said Jeffrey A. Golden, MD, executive vice dean of Research and Education and director of the Burns and Allen Research Institute at Cedars-Sinai. “Leveraging the scientific and technological ecosystems of both institutions will help advance the broader research landscape and bring advances in healthcare to individuals in our community and beyond.”

Cedars-Sinai Health Sciences University is advancing groundbreaking research and educating future leaders in medicine, biomedical sciences and allied health sciences. Learn more about the university.

Reid had been diagnosed with heart failure at Cedars-Sinai after experiencing fatigue and shortness of breath. The condition occurs when the heart is too weak to pump enough blood throughout the body, causing fluid to build up.

Reid told Good Morning America co-anchor Michael Strahan he initially dismissed his symptoms. He urged others—especially people of color—to seek medical care when something feels wrong.

“A lot of times, we don’t go because we don’t want the bad news, or we’re too busy just hustling, trying to make it from day to day,” Reid said. “And we … feel like we don’t got time, or we’ll get over it. Well, you might not.”

Jones told Good Morning America that during a follow-up visit, it was clear medications were no longer controlling Reid’s condition.

“He came in very swollen again,” she said, “and that is a little unusual in somebody who’s been started on treatment.”

DiChiacchio told Good Morning America that bloodwork revealed the condition was worsening and Reid needed an immediate heart transplant.

“So when we think about status for a heart transplant,” DiChiacchio said, “he was very high on that list because of how ill he was and really dealing with a kind of life or death situation.”

Days later a donor heart became available, and DiChiacchio and team successfully completed the transplant.

 Reid told Strahan he is grateful for a second chance at life.

“This thing is … a beautiful life,” he said. “And, you know, I wanna be around for it.”

According to the Centers for Disease Control and Prevention, 6.7 million U.S. adults have heart failure. Risk factors include high blood pressure, diabetes and coronary artery disease, though regular exercise, adequate sleep and proper nutrition can lower risk.

Click here to watch the entire segment of Good Morning America.

Preclinical Study Targets ‘Zombie’ Cells

Senolytics—a class of drugs that reduce chronic inflammation and tissue damage in aging cells—are shown to eliminate 30% to 70% of “zombie” cells in the body. These zombie cells, known as senescent cells, stop dividing and don’t die, ultimately contributing to a host of diseases of aging, including cancer.

A preclinical study from Cedars-Sinai, published in Aging Cell, had three key findings:

• Senolytic drugs purge the most harmful cells, leaving less-harmful senescent cells behind.
• These remaining “senolytic-resistant” senescent cells can be activated into tissue-damaging senescent cells by infections and other factors in the environment of senescent cells.
• A new class of drugs, “senosensitizers,” can enable senolytics to eliminate these lurking senolytic-resistant “ticking time bomb” cells.

Investigators found that in laboratory mice treated with senolytic drugs, the remaining senescent cells were less inflammatory and damaging than the cells removed by the treatment. Researchers also found that these remaining senescent cells, when activated into tissue-damaging cells by an inflammatory environment, become more vulnerable to senolytics than those in a stable environment.

Based on their findings that infections can make senescent cells become susceptible to senolytics, study authors theorize that targeting senescent cells with newly developed senosensitizers—and then senolytics—might allow more senescent cells to be removed than when using senolytics alone. This could remove senolytic-resistant senescent cells and reduce the impact of infections in previously apparently healthy older people.

“This drug combination, which is still in the preclinical phase, has the potential to target senescent cancer cells that persist after radiation and chemotherapy and may later reemerge as more aggressive disease,” said James Kirkland, MD, PhD, director of the Center for Advanced Gerotherapeutics and senior author of the study.

Additional Cedars-Sinai authors include Masayoshi Suda, Tamar Tchkonia, Selim Chaib, Larissa Langhi Prata, Tamar Pirtskhalava and Nino Giorgadze.

Additional authors include Utkarsh Tripathi, Vagisha Kulshreshtha, Bryan T. Piatkowski, Allyson K. Palmer, Christina Inman, Nathan Gasek, Ming Xu, Kurt O. Johnson, Yi Zhu, Renuka Kandhaya-Pillai, Stefan G. Tullius, Saranya P. Wyles, Rambabu Majji, Hari Krishna Yalamanchili and David B. Allison.

Funding: This work was supported by NIH grants R37AG013925 (J.L.K., T.T.), R33AG061456 (J.L.K., T.T.), R01AG066679 (M.X.), R01AG076642 (M.X.), R01AG064165 (S.G.T.), R01AG087387 (Y.Z.), the Connor Fund (J.L.K., T.T.), Robert J. and Theresa W. Ryan (J.L.K., T.T.), HF-GRO-­23-­ 1199148-­ 3 (J.L.K.), HF-­ GRO-­ 23-­ 1199262-­ 27 (Y.Z., M.S.), the JSPS Grants-­ in-­ Aid for Scientific Research Fund for the Promotion of Joint International Research (Fostering Joint International Research) 23KK0295 (M.S.), the Yamada Science Foundation (M.S.), and USDA/ARS grant CRIS 3092-­ 51000-­ 065-­ 003S (H.K.Y.) and the Noaber Foundation (J.L.K.). U.T. was supported by an American Heart Association predoctoral fellowship (917775).

Cedars-Sinai Study Links GLP-1RA Drugs to Risk of Chronic Cough

Patients who take the widely used Type 2 diabetes and obesity medications known as glucagon-like peptide-1 receptor agonists (GLP-1RAs) appear to be at increased risk of developing chronic cough, according to a new multicenter study led by Cedars-Sinai and published in JAMA Otolaryngology – Head & Neck Surgery.

GLP-1RA medications, marketed under many brand names, work by stimulating insulin release from the pancreas, lowering blood sugar and slowing digestion. As a result, these drugs may help people with Type 2 diabetes manage their blood sugar and help people with obesity lose weight.

Investigators reviewed 10 years of electronic medical records with data on more than 2 million Type 2 diabetes patients at 70 healthcare organizations. They compared records of individuals prescribed a GLP-1RA drug with those who were prescribed a non-GLP-1RA drug to treat diabetes, and found that GLP-1RA use was associated with a significantly increased risk of new chronic cough.

“Further research is needed to confirm the existence, strength and mechanisms of the association between GLP-1RA drugs and chronic cough,” said Anca Barbu, MD, associate professor in the Jim and Eleanor Randall Department of Surgery and the study’s corresponding author. “However, our findings highlight the importance of physicians and care providers asking patients with new-onset chronic cough about possible GLP-1RA use, and for healthcare providers prescribing these medications to discuss chronic cough as a possible side effect.”

The other Cedars-Sinai author is Neelaysh Vukkadala, MD.

Additional authors include Tyler J. Gallagher, MD, MPH; Diego E. Razura, MD; Albert Li, BA; and Ian Kim, PhD. 

Bodily Fluid Changes Linked to Poor Heart Surgery Outcomes

Patients who lose or gain a significant amount of fluid after certain elective heart surgeries are more likely to be readmitted to the ICU, stay longer in the hospital or die than patients whose fluid levels remain stable, according to a new study from Cedars-Sinai. The findings, published in Anesthesia & Analgesia, could help improve patient care.

Investigators reviewed data on 2,557 patients who underwent nonemergency coronary artery bypass grafts, valve surgeries or a combination of the two. They calculated each patient’s total fluid intake (including oral and intravenous fluids and blood products) and output (including urine, stool and surgical drains), based on measurements taken in the operating room and in the ICU after surgery.

“It remains unclear whether changes in cumulative fluid balances above 1.5 liters on the day of ICU discharge actually cause adverse outcomes or are just associated with them,” said senior author Joseph Ebinger, MD, MS, associate professor of Cardiology and director of the Coronary Intensive Care Unit and Clinical Analytics in the Smidt Heart Institute at Cedars-Sinai. “Further study is called for. In the meantime, our findings suggest that greater attention to such variations may help improve outcomes for cardiac surgery patients.”

Other Cedars-Sinai authors are Abirami Kumaresan, George Gill, Jesse Navarrette, Tao Shen, Milad Sharifpour, Dominic Emerson, Joanna Chikwe and Susan Cheng.

Funding: This study was supported in part by a grant from the International Anesthesia Research Society and NIH grant: K23-HL153888. The funding sources had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

Different Immune Cell Types Correlate with Breast Cancer Survival

The quantities of specific types of immune cells that appear in and around a breast cancer tumor are correlated with the prognosis for the patient, according to a new study led by Cedars-Sinai. The findings have implications for use of immunotherapy in this disease, the second leading cause of cancer deaths among women in the U.S.

The study was published in the peer-reviewed journal iScience.

Investigators analyzed images from 12,285 female breast cancers, including estrogen-positive breast cancer, the most common type, in which cancer cells have a protein that binds to the hormone estrogen; estrogen-negative breast cancer, in which the cells lack this protein, was also studied.

Using artificial intelligence (AI), investigators calculated the percentages of different types of immune cells within the tumors, in nearby connective tissue (known as stroma) and in total for both areas. They examined the relationship between these percentages and the likelihood that the patient would die from breast cancer over a certain period of time after diagnosis. Two types of immune cells, CD8+ and CD20+, were found to be associated with a better prognosis in estrogen-positive breast cancer patients, whereas another cell type, CD163+, was associated with a poorer prognosis. CD8+ and FOXP3+ immune cells were associated with a better prognosis in estrogen-negative breast cancer.

“Our findings suggest that the immune system is an important predictor of outcome in hormone-positive breast cancer,” said Paul Pharoah, MD, PhD, professor of cancer epidemiology in the Department of Computational Biomedicine at Cedars-Sinai and the study’s senior and corresponding author. “They support including this subset of patients in clinical trials of immune modulators, which could lead to improved treatments for women with this common cancer.”

Other authors include: Aaron J. Bernstein PhD, Renske Keeman MSc, Amber Hurson PhD, Fiona M. Blows PhD, Manjeet K. Bolla MSc, Jodi L. Miller PhD, Roger L. Milne PhD, Hugo Horlings MD, PhD, Alexandra J. van den Broek PhD, Clara Bodelon PhD, James M. Hodge JD, MPH, Alpa V. Patel PhD, Lauren R. Teras PhD, Federico Canzian PhD, Rudolf Kaaks PhD, Hermann Brenner MD, Ben Schöttker PhD, Sabine Behrens PhD, Jenny Chang-Claude PhD, Tabea Maurer DiplPsych, Nadia Obi PhD, Fergus J. Couch PhD1, H. Raza Ali PhD, Carlos Caldas MD, Irene Andrulis PhD, Gord Glendon MSc, Anna Marie Mulligan MD, Wilma Mesker PhD, Agnes Jager MD, PhD, Annette Heemskerk-Gerritsen PhD, Peter Devilee PhD, Scott M. Lawrence PhD, Jolanta Lissowska PhD, Karun Mutreja PhD, Thomas Ahearn PhD, Stephen Chanock MD, Maire A. Duggan MD, Diana Eccles PhD, J. Louise Jones MB ChB, PhD, Will Tapper PhD, Antoinette Hollestelle PhD, Maartje Hooning PhD, John Martens PhD, Carolien H.M. van Deurzen MD, PhD, Angela Cox PhD3, Simon S. Cross MB BS, Mikael Hartman MD, PhD, Jingmei Li PhD, Thomas C. Putti MD, Ute Hamann PhD, Muhammad Rashid MB BS, PhD, Ania Jakubowska PhD, Nicki Camp PhD, Melissa H. Cessna MD, Amy Berrington de Gonzalez DPhil, Katarzyna Bialkowska PhD, Jacek Gronwald PhD, Jan Lubiński MD, PhD, Siddhartha Yadav MD, Pietro Lio PhD, Doug F. Easton PhD, Mustapha Abubakar MD, PhD, Montse Garcia-Closas MD, DrPH,  and Marjanka K. Schmidt, PhD.

Acknowledgements: The authors thank the Histology and Genomics Cores at the Cancer Research UK Cambridge Institute for technical support, and all patients, researchers, clinicians, and administrative personnel who contributed to the studies taking part in BCAST.  The CPSII study investigators acknowledge the contribution to this study from central cancer registries supported through the Centers for Disease Control and Prevention's National Program of Cancer Registries and cancer registries supported by the National Cancer Institute's Surveillance Epidemiology and End Results Program.

BCAC was supported by Cancer Research UK grant: PPRPGMNov20\100002 and by core funding from the NIHR Cambridge Biomedical Research Centre (NIHR203312). The views expressed are those of the author(s) and not necessarily those of the NIHR or the Department of Health and Social Care.  The BCAST project was supported by the Horizon 2020 Research and Innovation Programs of the European Union B (grant number: 633784) and the NIHR Cambridge Biomedical Research Centre. AJB was supported by the NIH Oxford-Cambridge Scholars and Gates Cambridge Scholars programs. (The funding of the contributing studies is listed in a supplementary table in the article.)

Cedars-Sinai Health Sciences University is advancing groundbreaking research and educating future leaders in medicine, biomedical sciences and allied health sciences. Learn more about the university.

The study shows for the first time that Chlamydia pneumoniae can reach the retina—the tissue lining the back of the eye—where it triggers immune responses linked to inflammation, nerve cell death and cognitive decline.

“Seeing Chlamydia pneumoniae consistently across human tissues, cell cultures and animal models allowed us to identify a previously unrecognized link between bacterial infection, inflammation and neurodegeneration,” said Maya Koronyo-Hamaoui, PhD, professor of Neurosurgery, Neurology, and Biomedical Sciences at Cedars-Sinai Health Sciences University and the leading, senior author of the study. “The eye is a surrogate for the brain, and this study shows that retinal bacterial infection and chronic inflammation can reflect brain pathology and predict disease status, supporting retinal imaging as a noninvasive way to identify people at risk for Alzheimer’s.”

To conduct the study, researchers used advanced imaging, genetic testing and protein analysis to examine retinal tissue from 104 individuals, some with normal cognition, some with mild cognitive impairment and some with Alzheimer’s disease.

They found significantly higher levels of Chlamydia pneumoniae in the retinas and brains of people with Alzheimer’s disease than they found in people with normal cognition. The higher the bacterial levels detected, the more severe the brain changes and cognitive decline investigators found.

Higher levels of the bacterium were more common in people who carried the APOE4 gene variant, a known risk factor for Alzheimer’s disease.

Investigators also studied human neurons in the lab and in laboratory mice with Alzheimer’s disease. In both, infection with Chlamydia pneumoniae increased inflammation, nerve cell death and cognitive decline, showing the bacterium can accelerate disease processes. The infection also triggered production of amyloid-beta, the protein that accumulates in the brains of people with Alzheimer’s.

The findings were driven by co-first authors Bhakta Gaire, PhD, and Yosef Koronyo, MSc.

“This discovery raises the possibility of targeting the infection-inflammation axis to treat Alzheimer’s,” said Timothy Crother, PhD, co-corresponding author of the study and research professor at Cedars-Sinai Guerin Children's and the Department of Biomedical Sciences at Cedars‑Sinai.

The findings suggest that targeting chronic bacterial infection—and the inflammation it triggers—could represent a new treatment strategy. The research also supports potential use of the retina as a noninvasive way to help diagnose and monitor the disease.

Additional Cedars-Sinai authors include Bhakta Gaire, Yosef Koronyo, Jean-Philippe Vit, Alexandre Hutton, Lalita Subedi, Dieu-Trang Fuchs, Natalie Swerdlow, Altan Rentsendorj, Saba Shahin, Daisy Martinon, Edward Robinson, Alexander V. Ljubimov, Keith L. Black, Jesse Meyer, and Moshe Arditi.

Other authors include Julie A. Schneider, Lon S. Schneider, Debra Hawes, Stuart L. Graham, Vivek K. Gupta, and Mehdi Mirzaei.

Funding: This work has been supported by the NIH/NIA grants R01AG056478, R01AG055865, and AG056478-04S1 (M.K.H.), R01AG075998 (M.K.H. and T.R.C.), and Alzheimer’s Association grant AARG-NTF-21-846586 (T.R.C.). MKH is also supported by The Goldrich and Snyder Foundations. ER has been supported by The Ray Charles Foundation.

Cedars-Sinai Health Sciences University is advancing groundbreaking research and educating future leaders in medicine, biomedical sciences and allied health sciences. Learn more about the university.