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.

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.

Las células cerebrales que liberan dopamina —una sustancia química mensajera que interviene en el control del movimiento— la almacenan en pequeños sacos rodeados de membrana llamados vesículas sinápticas. Y estas vesículas son diferentes de las que utilizan las células cerebrales que liberan otras sustancias químicas mensajeras, según demuestra un estudio dirigido por investigadores de Cedars-Sinai Health Sciences University.

El estudio, publicado en Science Advances, podría contribuir a una mejor comprensión de la enfermedad de Parkinson, un trastorno del movimiento que provoca la muerte progresiva de las células cerebrales que liberan dopamina. La muerte de estas células causa los problemas de movimiento característicos de la enfermedad.

“Nuestra investigación arroja luz sobre las distintas formas en que las células cerebrales liberan mensajeros químicos, que utilizan para comunicarse entre sí”, dijo Katlin Silm, PhD, profesora asistente de Ciencias Biomédicas y Neurología y autora principal del estudio. “Identificamos diferencias clave entre las células cerebrales que liberan dopamina y las que liberan otras sustancias químicas cerebrales”.

Las vesículas sinápticas ayudan a las células cerebrales a comunicarse al fusionarse con la membrana celular y liberar su contenido en el espacio entre las células. En los cerebros de ratones de laboratorio, los investigadores descubrieron que las vesículas sinápticas que contienen dopamina transportan un conjunto de proteínas distinto al de aquellas que contienen otras sustancias químicas mensajeras.

“Nuestros hallazgos demuestran que la composición de una vesícula es fundamental para determinar cómo se liberan las sustancias químicas mensajeras del cerebro”, dijo Silm, quien también es investigadora científica del Board of Governors Regenerative Medicine Institute. “Las diferencias que identificamos ayudan a explicar las propiedades únicas de la liberación de dopamina y sientan las bases para explorar cómo esto afecta la estabilidad a largo plazo de las células cerebrales productoras de dopamina”.

Otros autores de Cedars-Sinai incluyen a Hrach Asmerian, Alexia J. Diaz, Jacob Alberts, Barathan Gnanabharathi, Anna M. Sanetra y Noah Carr.

Otros autores incluyen a Hongfei Xu, Juan A. Oses-Prieto, Poulomi Das, Alma L. Burlingame y Robert H. Edwards.

Financiamiento: Este trabajo recibió apoyo de The Larry L. Hillblom Foundation, subvención 2022-A-004-SUP (KS); Brain and Behavior Research Foundation, subvención 29845 (KS); National Institutes of Health, subvención R01NS138465 (KS); National Institutes of Health, subvención R01NS103938 (RHE); y National Institutes of Health, subvención R01NS129803 (RHE). La espectrometría de masas se realizó en el Mass Spectrometry Resource de UCSF, que cuenta con el apoyo de la Dr. Miriam and Sheldon G. Adelson Medical Research Foundation (JAO-P y ALB).

Nuevo Método Podría Aumentar el Valor de los Análisis de Sangre para Monitorear el Cáncer de Colon

Los análisis de sangre podrían convertirse en una herramienta más eficaz para monitorear la progresión del cáncer de colon y la respuesta al tratamiento, según un estudio dirigido por investigadores de Cedars-Sinai Health Sciences University. Los hallazgos, publicados en Experimental Hematology & Oncology, utilizaron perfiles unicelulares para analizar las células tumorales circulantes y las células no cancerosas presentes en la sangre de los pacientes.

“Nuestro método va más allá del tumor para comprender también la respuesta del paciente al cáncer”, dijo Jun Gong, MD, director médico de Cáncer Colorrectal de Cedars-Sinai y autor del estudio. “Podría ayudar a orientar decisiones de tratamiento más personalizadas basadas en el comportamiento del tumor y el estado del paciente”.

Los investigadores analizaron muestras de sangre de pacientes con cáncer colorrectal avanzado, examinando 10 características celulares diferentes y utilizando análisis unicelular para precisar sus hallazgos.

El método revela cambios importantes, como las medidas que adoptan las células tumorales para evadir al sistema inmunitario o la presencia de inflamación en células normales. Según Gong, estos cambios pasarían inadvertidos con las pruebas existentes.

Si estos hallazgos se validan en estudios de mayor tamaño, dijo Gong, este método podría complementar las herramientas existentes para monitorear el cáncer, incluidas las pruebas de diagnóstico por imágenes y los análisis de laboratorio estándar.

Otros autores de Cedars-Sinai incluyen a Francesca Aguirre, MD; Lisa Zhou, BS; Aaron Denmark, BS; Rocio Alvarez, MsC; y Daniel M. Kim, MD.

Otros autores incluyen a Gabriela Felix, PhD, y Megan P. Hitchins, PhD.

Financiamiento: Este estudio fue financiado en parte por la subvención R01CA252042 del NCI (MH), el Cedars-Sinai Cancer Developmental Fund (MH) y el ASCO Conquer Cancer Career Development Award (JG).

Declaraciones: J.G. informa haber recibido honorarios por consultoría y otros honorarios de las siguientes compañías: EMD Serono, Exelixis, Natera, Eisai, Janssen, Pfizer, Bayer, Taiho, Agenus, Seagen y Caper Labs. G.F., J.G. y M.H. tienen una solicitud de patente provisional (solicitud n.º 64/039,184) relacionada con el trabajo descrito en este manuscrito.

Gas de Sulfuro de Hidrógeno Está Relacionado con Daños Más Graves en el SII

Investigadores de Cedars-Sinai Health Sciences University han identificado cómo el exceso de gas de sulfuro de hidrógeno producido por ciertos microbios intestinales altera la actividad genética en el intestino delgado. Sus hallazgos, publicados en mSystems, ofrecen nuevos conocimientos sobre afecciones asociadas con el síndrome del intestino irritable (SII), uno de los trastornos gastrointestinales más comunes.

El sobrecrecimiento bacteriano del intestino delgado (SIBO, por sus siglas en inglés), el sobrecrecimiento de metanógenos intestinales (IMO) y la sobreproducción intestinal de sulfuro (ISO) son afecciones en las que los microbios productores de gases se multiplican excesivamente en el intestino delgado. Estos trastornos suelen estar relacionados con el SII.

“Nuestros resultados demuestran que ISO, IMO y SIBO son afecciones biológicamente distintas que requerirán diferentes enfoques de tratamiento”, dijo Mark Pimentel, MD, director ejecutivo del Medically Associated Science and Technology (MAST) Program de Cedars-Sinai y autor para correspondencia del estudio. “Los genes alterados en estas afecciones están relacionados con diversos síntomas, y comprender estos mecanismos nos ayudará a desarrollar mejores terapias para los pacientes”.

Los investigadores analizaron muestras de tejido del intestino delgado de pacientes y animales de laboratorio. Encontraron los cambios más extensos en la actividad genética en las muestras de pacientes con ISO, y cambios más limitados en las muestras de SIBO e IMO.

Los cambios genéticos afectaron la actividad inmunitaria, la absorción de líquidos, el movimiento de nutrientes a través del intestino, las defensas antioxidantes y la producción de energía celular. Estos hallazgos podrían ayudar a explicar por qué la sobreproducción de sulfuro de hidrógeno se ha asociado con diarrea, dolor abdominal y otros síntomas gastrointestinales graves en pacientes con SII con predominio de diarrea.

Pimentel dijo que se necesitan estudios de mayor tamaño que integren pruebas de aliento y perfiles del microbioma para validar aún más estos hallazgos e identificar cómo podrían contribuir al desarrollo de nuevas terapias.

Otros autores de Cedars-Sinai incluyen a 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 y Ruchi Mathur.

Otros autores incluyen a Zhe Lyu.

Financiamiento: Este estudio recibió apoyo principalmente del Medically Associated Science and Technology (MAST) Program de Cedars-Sinai Medical Center, Los Ángeles, California, y fue financiado en parte mediante donaciones privadas al MAST Program.

Declaraciones: Los doctores Pimentel, Mathur y Rezaie informan tener participación accionaria en APQ Health y haber recibido honorarios por licencias o consultoría relacionados con tecnologías de diagnóstico mediante pruebas de aliento de Gemelli Biotech y Brio-Medical. Los demás autores declaran no tener conflictos de intereses.

Cedars-Sinai Health Sciences University está impulsando investigaciones innovadoras y formando a los futuros líderes en medicina, ciencias biomédicas y ciencias de la salud afines. Más información.

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 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.

De acuerdo con el Instituto Nacional del Cáncer de Estados Unidos (National Cancer Institute), una mujer promedio tiene aproximadamente un 13% de probabilidad de desarrollar cáncer de mama a lo largo de su vida. Una mutación en los genes BRCA1 o BRCA2 eleva ese riesgo a entre 30% y 70%. Las pruebas de BRCA se recomiendan para mujeres con antecedentes personales o familiares de ciertos tipos de cáncer, una mutación conocida de BRCA en la familia o ascendencia judía asquenazí.

“Si bien la mayoría de las mujeres que se someten a pruebas genéticas no presentan una mutación en BRCA asociada con un mayor riesgo de cáncer, generalmente son remitidas a estas pruebas debido a antecedentes personales o familiares importantes de cáncer”, explicó Fahima Dossa, MD, PhD, oncóloga quirúrgica de Cedars-Sinai Cancer y autora principal del estudio. “El riesgo futuro de cáncer para estas mujeres no se había estudiado en profundidad, y nuestros hallazgos son los primeros en cuantificar ese riesgo para ayudarnos a orientar mejor a todas las mujeres que se someten a pruebas de BRCA”.

Al analizar los expedientes médicos de casi 16,000 mujeres que se realizaron pruebas de BRCA en Ontario, Canadá, entre 2007 y 2016, los investigadores encontraron que aquellas que obtuvieron un resultado negativo para una mutación en BRCA aún presentaban un 25% de riesgo de por vida de desarrollar cáncer de mama.

Además, las mujeres con una variante de significado incierto (VUS, por sus siglas en inglés), es decir, una variante genética sobre la que existe información limitada, tenían un riesgo de por vida del 30%, según los resultados.

El riesgo individual de cada paciente estuvo significativamente influenciado por sus antecedentes familiares. Entre las mujeres con una mutación positiva en BRCA, el riesgo de desarrollar cáncer de mama osciló entre aproximadamente 56% y 86%, dependiendo del número de familiares de primer grado con antecedentes de cáncer de mama u ovario.

“Con base en estos hallazgos, un médico podría recomendar mamografías o resonancias magnéticas de mama con mayor frecuencia a una paciente con BRCA positivo de entre 50 y 60 años sin antecedentes familiares de cáncer de mama, mientras que podría sugerir una mastectomía preventiva como opción para una paciente joven con BRCA positivo que tenga varios casos de cáncer de mama en su familia”, señaló Dossa.

Dossa agregó que las únicas mujeres del estudio cuyo riesgo de cáncer de mama fue similar al de la población general fueron aquellas con antecedentes familiares de cáncer y una mutación conocida de BRCA en la familia, que fueron evaluadas específicamente para esa mutación y cuyo resultado fue negativo.

“Este estudio recuerda a las pacientes la importancia de conversar con sus médicos sobre los resultados de las pruebas genéticas”, afirmó Dossa. “Por fin contamos con datos que pueden ayudar a orientar esas conversaciones”.

En julio, Cedars-Sinai inauguró el Cedars-Sinai Cayton BRCA Center, con el objetivo de ofrecer a pacientes con mutaciones en BRCA un programa integral de detección, orientación y tratamiento.

“Nuestra investigación de vanguardia respalda nuestros esfuerzos por brindar atención de excelencia y mejorar los resultados de estas pacientes”, afirmó Robert Figlin, MD, director interino de Cedars-Sinai Cancer. “Conectar la ciencia con la atención oncológica es el eje de todo lo que hacemos”.

Entre los demás autores del estudio se encuentran Kelly Metcalfe, RN, PhD; Zharmaine Ante, MSc; Ning Liu, PhD; Jordan Lerner-Ellis, PhD; Andrea Eisen, MD; y Nancy N. Baxter, MD, PhD.

Financiamiento: Este estudio recibió apoyo de ICES, financiado mediante una subvención anual del Ministerio de Salud de Ontario (MOH) y del Ministerio de Cuidados de Larga Duración de Ontario (MLTC). También recibió financiamiento de la Canadian Cancer Society (subvención n.º 315358) y de los Canadian Institutes of Health Research (CIHR) (subvención n.º 148470).

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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.

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.

Scientists from the Cedars-Sinai Board of Governors Regenerative Medicine Institute will share groundbreaking discoveries and discuss new frontiers in research at ISSCR 2026, the annual meeting of the International Society for Stem Cell Research, July 8-11 in Montreal.

Clive Svendsen, PhD, executive director of the institute, will present new data from a clinical trial of a cell-based therapy for retinitis pigmentosa, a degenerative eye disease that is mostly untreatable. This Phase 1/2a clinical trial of a subretinal injection of a human neural progenitor cell product found that the therapy is well tolerated and results in long-term engraftment. 

Arun Sharma, PhD, director of the Center for Space Medicine Research, will participate in a session co-sponsored by Cedars-Sinai on regenerative medicine in low Earth orbit. The focus of Sharma’s talk is accelerating development of organoid-based disease modeling and stem cell therapies due to increased access to microgravity, as well as in-space biomanufacturing. 

Tynhinane Hamidouche, PhD, a postdoctoral scientist in the lab of Dmitriy Sheyn, PhD, is presenting research on a stem cell–based therapy for intervertebral disc degeneration and chronic low-back pain. Using human induced pluripotent stem cells, the team generates cells that produce the matrix material found inside the discs.

Paul Linesch, PhD, a postdoctoral scientist in the Svendsen Lab, is presenting research on an inducible DNA system, adapted using new technology developed at Cedars-Sinai, to turn specific genes on and off. The system could improve direction of stem cell differentiation and open new possibilities for cellular therapy. 

Molly Easter, PhD, a postdoctoral scientist in the lab of Tyler Pierson, MD, PhD, will present research on a rare brain development disorder linked to the GATAD2B gene, which helps control how genes turn on and off during brain growth. Using brain organoids generated from patient-specific induced pluripotent stem cells, the researchers found signs that the normal layering and patterning of the cortex may be disrupted in this disorder. 

Dhruv Sareen, PhD, associate professor of Biomedical Sciences and founding director of the Cedars-Sinai Biomanufacturing Center, is presenting research on the integration of an in situ seed plating system into the center’s manufacturing workflow to streamline production of complex induced pluripotent stem cell lines for clinical-grade and research use.

Avinash Srivastava, PhD, a biomedical scientist in the Cedars-Sinai Biomanufacturing Center, is presenting information on the center’s proprietary integrated induced pluripotent stem cell biomanufacturing platform. The platform integrates standardized manufacturing with advanced bioprocessing to facilitate the scalable production of high-quality engineered cell therapies.

Media Contact

To schedule an interview with a Cedars-Sinai expert, contact Christina Elston at christina.elston@cshs.org or 626-298-0702.

“Continuity of care throughout the lifespan is important for sarcoma patients,” said Leo Mascarenhas, MD, director of the Adult and Pediatric Sarcoma Program and the Division of Pediatric Hematology/Oncology at Cedars-Sinai Cancer. “Our multidisciplinary expertise, which includes pathology, radiation oncology and surgical care, means both adults and children with sarcoma can receive all of their care in one place.”

Mascarenhas is a professor of Pediatrics and Medicine at Cedars-Sinai Health Sciences University and pediatric hematologist-oncologist who has more than 25 years of clinical and research experience. He has led multi-institutional clinical trials for Ewing sarcoma, rhabdomyosarcoma, osteosarcoma and other rare pediatric solid tumors.

Additional Cedars-Sinai Sarcoma Experts

James Hu, MD, associate director of the Sarcoma Program, has more than 30 years of clinical experience in medical oncology. His research focuses on evaluating novel biomarkers and liquid biopsy methods to improve the treatment of bone and soft tissue sarcomas and examining risk factors for young patients facing rare forms of cancer.

Earl Brien, MD, surgical director of the Sarcoma Bone Tumor Program and professor of Orthopaedics, is an orthopedic oncology specialist. His research focuses on surgical strategies for treating complex soft tissue sarcomas, improving surgical techniques for the removal of bone cancers while avoiding amputations, and use of circulating tumor DNA to noninvasively assess treatment response.

Jason Chan, MD, is a board-certified medical oncologist who specializes in the care of people with sarcoma, including desmoid tumors, gastrointestinal stromal tumors (GIST), as well as other soft tissue and bone sarcomas. He studies how cancers adapt and become resistant to treatment, with a focus on the ability of cancer cells to shift into different cell states that may allow them to grow, spread and survive therapy.

Fahima Dossa, MD, PhD, surgical oncologist in the Jim and Eleanor Randall Department of Surgery, primarily treats soft tissue sarcoma, including gastrointestinal stromal tumors (GIST), liposarcoma, leiomyosarcoma and desmoid tumors. She also specializes in treatment of retroperitoneal sarcoma, which develops deep in the fat or muscle of the abdomen, using a specific operative technique to help prevent recurrence.

Behrooz Hakimian, MD, is an assistant professor of Radiation Oncology whose research merges clinical trial exploration with advanced radiation oncology techniques, focusing on patient safety during therapy for complex sarcomas and soft tissue tumors.

Mitchell Kamrava, MD, is a professor of Radiation Oncology whose sarcoma research centers on optimizing preoperative radiation, reducing treatment timelines and predicting post-surgical complications. He has been a co-investigator on pivotal clinical trials evaluating a condensed five-day preoperative radiation regimen for high-risk primary soft tissue sarcomas.

Eugene Kim, MD, is a professor of Surgery and Pediatrics, director of the Division of Pediatric Surgery and vice chair of the Department of Surgery. He is recognized for his expertise in pediatric surgical oncology and he is a key member of the sarcoma team.

Joseph Schwab, MD, director of Spine Oncology in the Department of Orthopaedics, is a specialist in managing sarcomas of the spine—including rare, complex tumors like chondrosarcomas and chordomas—in adults. His research focus includes use of algorithms and machine learning to build tools that optimize clinical decision-making for bone and soft tissue tumors.

Media Contact

To schedule an interview with a Cedars-Sinai sarcoma expert, contact Christina Elston at christina.elston@cshs.org or 626-298-0702.

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.

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.

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 new

“The generosity and foresight of the Cayton Goldrich Family Foundation gave us the resources to conduct outreach and coordinate care for these patients,” said Cristina Ferrone, MD, chair of the Jim and Eleanor Randall Department of Surgery at Cedars-Sinai. “By bringing together our dedicated physicians and recruiting top talent from around the country, we are making this centralized BRCA center unlike any other.”

Individuals of Ashkenazi Jewish descent, and those with family history of breast, ovarian, prostate or pancreatic cancer, or people who have been diagnosed with one of these cancers, should be screened for BRCA1 and BRCA2 mutations, Ferrone said.

Cancer Screenings

“This center will provide every relevant service: comprehensive risk assessment, state-of-the-art surveillance, prevention strategies, clinical trials, and access to the latest scientific discoveries,” said Farin Amersi, MD, a surgical oncologist who treats patients with BRCA mutations. “More importantly, it will create a true home for patients and families facing hereditary cancer risk.” 

A patient’s first visit to the center begins with genetic counseling to help patients understand their unique cancer risk. For women, the initial visit also includes a breast MRI or mammogram, and a pelvic ultrasound and blood test to screen for ovarian cancer. Men undergo imaging to screen for breast cancer and an exam and blood test to screen for prostate cancer. For pancreatic cancer, both men and women may have abdominal imaging and discuss the possibility of endoscopy screening, depending on their individual risk.

“At many other institutions, patients diagnosed with a BRCA mutation have to make appointments for each of these screenings separately, with different physicians,” Amersi said. “Our patients will have all their screenings—and receive their test results—in one visit. This will help relieve the anxiety of juggling multiple appointments and waiting to learn the results of these tests.”

The process condenses what could be eight to 12 different appointments into a single day, Ferrone said.

“For patients with BRCA mutations, these screenings are repeated every six to 12 months, so you can imagine how disruptive separate appointments are for patients, many of whom work and have families,” Ferrone said.

Based on their test results, patients meet with a team of specialists about the best path forward, taking into account the patient’s age, fertility goals and individual cancer risk.

Preventive Treatment

For breast and ovarian cancer prevention, patients and their care team discuss the need and timing for possible preemptive surgery.

BRCA1 and BRCA2 mutations have slightly different risks associated with them, said Marla Scott, MD, a gynecologic oncologist.

“People with BRCA1 mutations have roughly a 40% higher risk for gynecologic cancers, and are a younger average age when cancer tends to appear,” Scott said. “This means we have a discussion about removing the fallopian tubes and ovaries, as well as consideration for hysterectomy and mastectomy, between ages 35 and 40.”

A reproductive endocrinologist is on-site to discuss fertility preservation—including egg and embryo freezing and in-vitro testing and fertilization—as well as hormone replacement options to manage symptoms of surgically-induced menopause, Scott said.

For people with BRCA2 mutations, there is a slightly lower increased risk of gynecologic cancer, and age of cancer onset tends to be about 10 years later, allowing doctors to delay preventive surgeries, Scott said.

“With the exception of regular breast exams, patients may get to ‘graduate’ out of further screening for gynecologic cancers if they have a risk-reducing surgery and show no signs of cancer,” Scott said.

Scott added that while managing cancer risk can be challenging for people with a BRCA mutation, having a place they can go for guidance is empowering. The hope, Ferrone said, is that community outreach efforts will bring these benefits to even more patients.

“We are incredibly fortunate to be able to offer free genetic testing in high-risk populations in the near future,” Ferrone said. “This will help us identify more at-risk patients and get them enrolled in the appropriate programs to help them manage their risk and preserve their 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.

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.

Andrew Hendifar, MD, medical director of the Cedars-Sinai Cancer Clinical Trials Office and professor of Medicine, is available to discuss late-breaking, embargoed results of a trial of a new therapy for advanced pancreatic cancer, as well as Phase II results from a trial of a combination therapy that targets specific genetic mutations in pancreatic cancer cells.

Additional Cedars-Sinai Experts

Leslie Ballas, MD, professor of Radiation Oncology, will participate in a panel discussion and can discuss evidence related to use of biomarkers or circulating tumor DNA in treatment decisions for patients with muscle-invasive bladder cancer.

Fahima Dossa, MD, PhD, a surgical oncologist, will present research on which patients with high-risk localized soft tissue sarcoma are most likely to benefit from chemotherapy.

Stephen Freedland, MD, director of the Center for Integrated Research in Cancer and Lifestyle, will present a post hoc analysis of the EMBARK trial in advanced prostate cancer, detailing testosterone recovery following treatment suspension. Freedland can also discuss research from his lab on use of olaparib, an enzyme blocker, in metastatic castration-resistant prostate cancer, and statin use in prostate cancer patients receiving hormone treatment after prostate-removal surgery.

Lawrence Liu, MD, a hematology oncologist, will present research on recent advances in CAR T-cell therapies for patients with relapsed multiple myeloma. The work involves mezigdomide, part of a new drug class in myeloma, following infusion with idecabtagene vicleucel, a genetically modified CAR T therapy derived from the patient’s own cells.

Arsen Osipov, MD, associate professor of Medicine and medical director of Pancreatic Cancer, can discuss research from his lab on the comprehensive molecular profiles associated with variants of the KRAS gene and patient survival in pancreatic cancer. KRAS mutations are found in more than 90% of pancreatic cancer cases.

Karen Reckamp, MD, professor of Medicine and director of the Division of Medical Oncology, can discuss the treatment landscape for non-small cell and small cell lung cancer. She can explain research from her lab on a machine learning approach for predicting immune-related pneumonitis, a noninfectious lung inflammation that can occur following treatment with immune checkpoint inhibitors. She can also speak about new data from Lung MAP, a clinical trial designed to efficiently test treatments for advanced non-small cell lung cancers. And she will make a presentation on support of academic nonclinical efforts for cancer investigator faculty at the Association of American Cancer Institutes.

Kamya Sankar, MD, assistant professor of Medicine and co-director of the Thoracic Disease Research Group, will present an analysis of factors associated with early cachexia—also known as cancer wasting disease—in metastatic non-small cell lung cancer. She can also speak about treatment of both non-small cell and small cell lung cancer.

From The Angeles Clinic and Research Institute

Mark Faries, MD, surgical oncologist and professor of Surgery, can discuss a five-year update from the KEYNOTE-942 study in resected melanoma and a new study of lymph node resection versus therapeutic dissection in advanced melanoma, as well as recurrence in advanced melanoma across time.

Erwin Grussie, MD, a hematology oncologist, can discuss results from the Targeted Agent and Profiling Utilization Registry (TAPUR) study testing targeted therapies in patients with solid tumors.

Omid Hamid, MD, professor of Medicine and chief of Translational Research and Immuno-Oncology, will present results from a study of a medication that blocks the action of cortisol in patients with advanced solid tumors, as well as a study of causes of limited immunotherapy response in melanoma. He can also discuss new results from three trials of therapies in advanced melanoma.

Inderjit Mehmi, MD, a hematology oncologist, can discuss the association of prior immunotherapy treatment with limited response to subsequent immunotherapy in melanoma.

Media Contact

To schedule an interview, contact Christina Elston at christina.elston@cshs.org or 626-298-0702.

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.

The project, which includes investigators from UCLA, the University of Southern California (USC), and the University of Münster in Germany, is funded by a three-year, $9 million grant from Aligning Science Across Parkinson’s, in partnership with The Michael J. Fox Foundation for Parkinson’s Research.

In the debilitating neurodegenerative condition, one of the major problems is that brain cells producing dopamine—the chemical in the brain that helps nerves coordinate muscle movement—die more rapidly than normal. As these cells die off, patients experience tremor, stiffness, and movement and balance issues.

“We think that Parkinson’s disease is caused by a combination of genetic traits in the patient and environmental exposures—especially to certain pesticides and air pollution,” said Clive Svendsen, PhD, executive director of the Cedars- Sinai Board of Governors Regenerative Medicine Institute and one of the principal investigators of the study. “It seems the genes load the gun while the environment pulls the trigger. With this grant, we will generate lines of stem cells from people living in a pesticide-treated area in the San Fernando Valley and attempt to figure out why some developed Parkinson’s and some did not.”

Svendsen said that only about 5%-10% of Parkinson’s disease cases are caused by a single genetic mutation, and evidence is building that mutations in many other areas of the genome may also contribute to disease.  

“If you have mutations in an array of different genes, we know that increases your risk for developing Parkinson’s,” Svendsen said. “We are trying to determine which of those genetic vulnerabilities interact with pesticides—and how. If we can figure that out, we can begin to think about new approaches to treatment.”

The team will recruit groups of relatives—some who developed Parkinson’s disease and some who did not. Investigators will reprogram participants’ cells to create induced pluripotent stem cells, which they can then turn into dopamine-producing neurons that replicate the brain cells at risk in Parkinson’s patients. They will then expose those cells to the pesticides or air pollution present where the participants live.

“By investigating how the environment and a person’s unique genetics interact to drive Parkinson’s, this team is uncovering the diverse biological drivers of the disease,” said Sonya Dumanis, PhD, managing director of ASAP. “This is exactly the kind of bold, integrative science the Collaborative Research Network is designed to accelerate. With a better understanding of these disease mechanisms, we can lay the groundwork for new, personalized therapeutics and better outcomes for Parkinson's patients."

 The investigators’ theory is that the dopamine neurons generated from people with Parkinson’s disease will die more quickly after pesticide exposure than the neurons from family members exposed to the same pesticides or air pollution who did not develop the disease.

“If that turns out to be the case, we can compare the genetic makeup of those individuals, and the proteins their genes express, and try to figure out what triggered the development of Parkinson’s disease in some of them but not others,” Svendsen said.

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.).

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Through more than 20 talks, panels, symposia and poster presentations, they will cover topics ranging from cancer biology to the tumor microenvironment, biomarkers that can guide cancer treatment, clinical trial results, and the role of AI in precision oncology.

Late-Breaking Presentation

Inderjit Mehmi, MD, medical oncologist at Cedars-Sinai The Angeles Clinic and Research Institute, will deliver a late-breaking oral presentation about an ongoing Phase I/IIa study of the immune checkpoint inhibitor GV20-0251 in patients with advanced melanoma that is resistant to anti-PD1 and other standard therapies. The presentation builds on clinical data presented at ASCO 2025 and will report translational findings from the study.

Additional Cedars-Sinai Cancer Experts and Topics

Eytan Ruppin, MD, PhD, an investigator at the Translational Research Institute and the Jim and Eleanor Randall Department of Surgery, will chair an Advances in Technology session exploring approaches for harnessing AI to learn about the spatial organization of human tissues. Speakers will describe computational approaches to spatial omics experiments, recent studies on developing agents that facilitate the analysis and characterization of pathology slides and spatial transcriptomics data, and ways to infer spatial biology and cancer treatment response biomarkers directly from histopathology slides.

Sergei Grivennikov, PhD, professor of Medicine and Biomedical Sciences, will co-chair a mini-symposium on the tumor microenvironment and its role in tumor evolution and immune system evasion.

Karen Reckamp, MD, a thoracic medical oncologist and director of the Division of Medical Oncology, will present final results from Pragmatica-Lung, a prospective randomized clinical trial with a pragmatic design that evaluated ramucirumab plus pembrolizumab versus standard of care in more than 800 patients with stage 4 or recurrent non-small cell lung cancer.

Cedars-Sinai investigators will also present research on:

• New understanding of and treatments for breast cancer
• Disparities in heart disease deaths among breast cancer patients
• Antitumor responses in pancreatic and breast cancer
• Radiation and antitumor therapies in prostate cancer
• Immune rejection and antitumor activity in bile duct cancer
• The tumor microenvironment’s role in pancreatic cancer spread

Experts Available to Comment

Cedars-Sinai investigators are available to discuss their work and other news coming out of the meeting. To schedule an interview, contact Christina Elston at christina.elston@cshs.org or 626-298-0702.

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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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.

Now, thanks to a $5 million gift from the Elaine and Eduardo Saverin Foundation, Graham enters updates into an app on his phone every few days and his care team can view them in real time.

“I use it every other day, at different times of the day, and I hope that helps the care team have a better idea of how my medication is working,” Graham said. “I enjoy it. It keeps me thinking about what I might be able to do better to help myself.”

Cedars-Sinai is helping Graham and other patients by expanding its use of the app, called Kneu Health.

Doctors all over the world who care for patients with Parkinson’s disease face the same dilemma, said Michele Tagliati, MD, vice chair of Neurology and director of the Movement Disorders Division at Cedars-Sinai.

“At each checkup you ask a patient who has a neurological disorder and may be in their 70s or 80s how they’ve been doing for the past three to six months,” Tagliati said. “And you base your whole treatment plan on what they tell you.”

The Kneu Health app, which Tagliati is testing with Graham and other patients, gives doctors more frequent updates. Every few days patients use the app to perform exercises—such as holding the phone in front of their face to check for tremor, walking so the phone’s accelerometer can check their balance, or performing exercises that test their memory or reaction time.

Patients also can enter information about their sleep quality and other symptoms of the movement disorder, in which brain cells progressively deteriorate.

The information feeds directly into the Cedars-Sinai electronic medical record (EMR) and the app produces a summary for doctors to review. It also sends an alert if the data suggests a patient is at risk for falling or other serious issues.

“This allows us to intervene instead of waiting for the patient’s next visit,” Tagliati said. “Rather than unknowingly having a patient spend months on a medication that isn’t working or having them end up in the emergency department because of a fall, we can change their medication or have them use a walker.”

Graham was first diagnosed with Parkinson’s disease in 2018. He takes daily medications, uses an online speech pathology program, practices yoga and Pilates, and sees Tagliati every three months for botulinum toxin injections to help control his involuntary spasms.

Graham said he finds the app intuitive and easy to use and likes the fact that he can check in whenever he wants—and choose what he would like to work on.

The Elaine and Eduardo Saverin Foundation’s gift will fund the hiring of three physician assistants or nurse practitioners to help monitor the large population of patients with Parkinson’s disease followed at Cedars-Sinai, which currently number more than 800.

“We're supporting Cedars-Sinai's Parkinson's disease program because it addresses a critical gap in care by ensuring that patients maintain their quality of care even in outpatient settings,” said Elaine Saverin, chairwoman of the foundation. “Technological innovations like the Kneu Health app can have profound ripple effects for thousands living with Parkinson's.”

The additional staff funded by the gift will also help patients with Parkinson’s disease who are hospitalized for reasons unrelated to their condition, such as an infection or the need for emergency surgery.

“When a patient with Parkinson’s disease is admitted to Cedars-Sinai, we want to make sure the neurology care team knows about it,” Tagliati said. “These patients are at risk of prolonged hospital stays or other complications if their prescribed medications aren’t given on time, or if they are prescribed medications that can be harmful when taken with Parkinson’s medications.”

Cedars-Sinai has created an electronic dashboard to track and improve the care of these patients. The additional dedicated staffing will mean a nurse practitioner or physician assistant is available to monitor the dashboard and ensure hospitalized patients with Parkinson’s disease are receiving the best possible care.

Kneu Health participated in Cedars-Sinai’s Accelerator Program in 2024, and the Cedars-Sinai Intellectual Property Company recently invested in the company.

“This innovative approach to treating people with Parkinson’s disease is something that is done at only a few hospitals around the country,” said Nirdesh Gupta, PhD, managing partner in the Cedars-Sinai Intellectual Property Company. “Thanks to the Elaine and Eduardo Saverin Foundation, the participation of our patients and advances in technology, we now have the opportunity to improve the standard of care for Parkinson’s patients here at Cedars-Sinai and, ultimately, on a global scale.”

Read More on Stories and Insights: Understanding Parkinson’s Disease

“Después de 35 años de matrimonio, mi corazón sigue cantando cuando la miro”, dijo Philip. “Mi cáncer fue más duro para Linda que para mí, y el cáncer de ella fue más duro para mí que para ella. Cuando uno de los dos estaba enfermo, el otro llenaba los vacíos. Así es como vivimos nuestras vidas: lo que uno necesita, el otro lo da”.

El cáncer de páncreas de Philip fue detectado a principios de 2024 durante una resonancia magnética no relacionada de sus riñones. Arsen Osipov, MD, director médico de la Clínica Multidisciplinaria de Cáncer de Páncreas y de los Programas Multidisciplinarios de Cáncer e Integración en Cedars-Sinai, y oncólogo de Philip, dijo que fue un golpe de suerte.

“Fue diagnosticado en una etapa curable, antes de que el cáncer se propagara”, explicó Osipov. “Solo entre el 10% y el 20% de los pacientes con cáncer de páncreas reciben un diagnóstico tan temprano”.

Philip fue uno de los primeros pacientes en acudir a la clínica multidisciplinaria, donde en un solo día se reunió con oncólogos médicos, oncólogos radioterapeutas, cirujanos, gastroenterólogos y otros especialistas. Juntos acordaron un plan de tratamiento: cuatro meses de quimioterapia, seguidos de radiación y una cirugía compleja conocida como el procedimiento de Whipple.

“Es una operación compleja en la que se extirpa lo que se conoce como la cabeza del páncreas, la primera parte del intestino delgado, la vesícula biliar y el conducto biliar”, explicó Nicholas Nissen, MD, director de Cirugía Hepatobiliar y Pancreática. “Luego, estas estructuras se reconectan para restaurar la función normal”.

Antes, este procedimiento requería incisiones grandes, pero gracias a que la radiación y la quimioterapia redujeron con éxito el tumor de Philip, Nissen pudo realizar la cirugía de forma robótica.

“Esto nos permite hacer incisiones más pequeñas, con menor riesgo de complicaciones y un tiempo de recuperación más corto para el paciente”, dijo Nissen.

Tras cuatro días en el hospital y dos meses más de quimioterapia, Philip fue declarado libre de cáncer en junio.

Pero la pareja solo tuvo unos días para celebrar.

Menos de una semana después de que Philip recibiera la noticia, Linda fue diagnosticada con cáncer de mama tras una mamografía de rutina.

“Como sistema de salud, nos enfocamos en la detección y siempre estamos desarrollando nuevas formas de identificar el cáncer de manera temprana”, dijo Robert Figlin, MD, director interino de Cedars-Sinai Cancer. “En ambos casos, la detección temprana fue clave para lograr el mejor resultado posible”.

Aun así, el diagnóstico fue un shock para Philip y Linda.

“Fue algo increíble”, dijo Linda. “Pero ya habíamos pasado por todo el proceso con Phil. Su cirugía fue mucho más seria que la mía, y le fue tan bien que me sentí mucho más tranquila”.

Ella también tuvo suerte, señaló Armando Giuliano, MD, director de Oncología Quirúrgica de Mama en Cedars-Sinai Cancer y cirujano de Linda.

“Era un cáncer detectado por estudios de rutina, sin síntomas. No se puede palpar, no causa dolor ni secreción”, explicó Giuliano. “La única forma de detectar un cáncer así es mediante pruebas de detección. Y esos son los cánceres más pequeños y los más fáciles de curar”.

Giuliano pudo realizar una terapia conservadora de mama conocida como mastectomía parcial o lumpectomía.

“Extirpamos el área del seno que contiene el cáncer, asegurándonos de obtener márgenes limpios”, dijo. “Luego realizamos una reconstrucción interna para que el seno luzca lo más natural posible”.

También realizó un procedimiento que él mismo desarrolló y continúa perfeccionando en Cedars-Sinai, llamado biopsia del ganglio linfático centinela, mediante el cual se extraen uno o dos ganglios para confirmar que el cáncer no se haya diseminado más allá del seno.

“Hizo un trabajo tan hermoso que, si alguien viera mi seno, no sabría que tuve una cirugía”, dijo Linda.

El cáncer de Linda era un carcinoma ductal infiltrante, un tipo de cáncer que comienza en los conductos mamarios y puede propagarse a otras partes del cuerpo. Además, era HER2 positivo, por lo que requirió tratamiento adicional.

“Aproximadamente el 20% de los cánceres presentan una sobreexpresión de la proteína HER2, lo que los hace más agresivos y con mayor riesgo de propagación”, explicó la oncóloga médica Philomena McAndrew, MD. “Por esta razón, después de la cirugía tratamos a Linda con quimioterapia e inmunoterapia, seguidas de radioterapia. Linda respondió increíblemente bien en cada etapa”.

Un elemento importante para Linda fue la recomendación de McAndrew de usar un gorro de enfriamiento para ayudar a prevenir la caída del cabello durante la quimioterapia.

“Estoy tan feliz de haberlo usado”, dijo Linda.“ La Dra. McAndrew me explicó que cuando las mujeres pierden el cabello, puede ser muy traumático. Al mirarse al espejo, se dan cuenta de lo enfermas que están. Afortunadamente, eso no me pasó, y estoy muy agradecida”.

Linda completó su último tratamiento de radiación en enero y continuará con terapia preventiva durante cinco años. Ella y Philip también se someterán a exámenes de seguimiento de forma regular.

Por ahora, planean viajar desde su “casa en la ciudad”, en Culver City, hasta su residencia principal en Lake Arrowhead para pasar tiempo con amigos que no han visto en un tiempo.

Y luego continuarán su camino juntos, en la salud y en la enfermedad.

“Nos vamos de crucero a Hawái a finales de febrero”, dijo Linda. “Estamos tratando de llenar de diversión los próximos 20 años”.

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Both experts, who were featured in separate episodes, discussed liquid biopsy. This type of test looks for small fragments of DNA shed by cancer cells—circulating tumor DNA (ctDNA)—in the patient’s blood.

“We use liquid biopsy a lot,” Reckamp told BackTable, noting that there are at least 10 biomarkers in the blood that help oncologists determine the best treatments for lung cancer patients. “We're using those to think about prognosis, to look at the biology, to help understand whether we need to change systemic therapies, and whether there are new targeted therapies that are available.”

Gong discussed colorectal cancer studies presented at the European Society for Medical Oncology conference in October, including two that focused on liquid biopsy and ctDNA. He noted that monitoring colorectal cancer patients for ctDNA is gaining in popularity but is not yet part of established guidelines for directing treatment.  

“For now, I tend to use it on a case-by-case basis,” Gong told BackTable. “It's really with high-risk stage 2 or stage 3 patients that we discuss the option of circulating tumor DNA, but with the caveat that patients understand that this is really prognostic right now, and we don't have a high-level, established guideline for what to do with these results.”

Listen to the complete episodes featuring Reckamp and Gong on BackTable.

“After 35 years of marriage, my heart still sings when I look at her,” Philip said. “My cancer was much worse on Linda than it was on me, and her cancer was worse on me than it was on her. Whichever one of us was sick, the other one filled in the gaps. But that’s the way we normally live our lives. Whatever one needs, the other one provides.”

Philip’s pancreatic cancer was detected in early 2024 during an unrelated MRI of his kidneys. Arsen Osipov, MD, medical director of the Pancreatic Cancer Multidisciplinary Clinic and Multidisciplinary Cancer Programs and Integration at Cedars-Sinai, Philip’s oncologist, said it was a stroke of luck.

“He was diagnosed at a curable stage, before the cancer had spread,” Osipov said. “Only 10 to 20% of patients with pancreatic cancer are diagnosed this early.”

Philip was one of the first patients to visit the multidisciplinary clinic, where in a single day he met with medical oncologists, radiation oncologists, surgeons, gastroenterologists and other experts, and agreed on a treatment plan: four months of chemotherapy, followed by radiation and a complicated surgery called a Whipple procedure.

“This is a complex operation where we remove what’s called the head of the pancreas, the first part of the small intestine, the gallbladder and the bile duct,” said Nicholas Nissen, MD, director of Hepatobiliary and Pancreatic Surgery. “After removal, these structures are reattached to restore normal function.”

This procedure once required large incisions, but because radiation and chemotherapy successfully shrank Philip’s tumor, Nissen was able to perform the procedure robotically.

“This allows us to make smaller incisions, with lower risk of complications and a shorter recovery time for the patient,” Nissen said.

After four days in the hospital and two more months of chemotherapy, Philip was declared cancer-free in June.

But the couple had just a few days to celebrate.

Less than a week after Philip learned he was cancer-free, Linda was diagnosed with breast cancer after undergoing a routine mammogram.

“As a health system, we focus on screening and are always developing new ways to detect cancer early,” said Robert Figlin, MD, interim director of Cedars-Sinai Cancer. “For both of these patients, early detection was key to the best possible outcome.”

Still, the diagnosis was a bit of a shock to Philip and Linda.

“It was sort of unbelievable,” Linda said. “But we had been through the whole process with Phil, and his surgery was much more serious than mine, and he did so well that I felt much more comfortable.”

And she, too, was lucky, said Armando Giuliano, MD, director of Breast Surgical Oncology at Cedars-Sinai Cancer and Linda’s surgeon.

“She had a screen-detected cancer that has no symptoms. You can't feel it. It causes no pain, no discharge,” Giuliano said. “The only way you can detect a cancer like that is with breast cancer screening. And those cancers are the smallest cancers—the cancers that are the easiest to cure.”

Giuliano was able to perform a breast-sparing therapy known as a partial mastectomy or lumpectomy.

“We remove the area of the breast that has cancer, all the way around so that we have clean margins,” Giuliano said. “And then we do an internal reconstruction to make the breast look as natural as possible.”

Giuliano also performed a procedure he pioneered, which he continues to develop at Cedars-Sinai, called a sentinel lymph node biopsy, removing one or two lymph nodes to be certain the cancer had not spread beyond the breast.

“He did such a beautiful job that if you were to look at my breast, you would not know I had had surgery,” Linda said.

Linda’s cancer was an infiltrating ductal carcinoma, a cancer that starts in the breast ducts and can spread throughout the body. It was also HER2 positive, so it required further treatment.

“Around 20% of cancers have this overexpression of the HER2 protein, which makes them more aggressive and at higher risk of spreading,” said medical oncologist Philomena McAndrew, MD. “For this reason, after Linda’s surgery we treated her with chemotherapy and immunotherapy. We followed that with radiation therapy, and Linda did incredibly well throughout each of these steps.”

One important element for Linda was McAndrew’s recommendation to use a cooling cap to help avoid hair loss during chemotherapy.

“I'm so thrilled that I did,” Linda said. “Dr. McAndrew told me that when women lose their hair, it's very traumatic. When they look in the mirror, they realize how sick they are. Fortunately, that didn’t happen to me, and I was so grateful.”

Linda completed her final radiation treatment in January and will continue preventive therapy for five years. She and Philip will also have regular follow-up screenings.

But for now they are headed from their “city house” in Culver City to their main house in Lake Arrowhead, to spend time with friends they haven’t seen in a while.

Then they’ll continue their journey, in sickness and in health, together.

“We’re going on a cruise to Hawaii at the end of February,” Linda said. “We're just trying to pack some fun into the next 20 years.”

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.

These outcomes place the medical center at the top of rankings recently released by the Center for International Bone and Marrow Transplant Research (CIBMTR). Cedars-Sinai is one of just seven adult transplant centers out of 176 in the U.S. where patient survival after transplant is significantly better than predicted.

“We have a carefully chosen approach to pretransplant conditioning and graft-versus-host disease prevention for our patients, which plays a vital role in our strong survival outcomes,” said John Chute, MD, director of the Division of Hematology and Cellular Therapy at Cedars-Sinai Cancer. “We also have a dedicated system for keeping patients in touch with their care team, which helps identify problems before they become serious.”  

The greatest risk to stem cell transplant patients is during the first 100 days after transplant, said Ronald Paquette, MD, clinical director of the Stem Cell and Bone Marrow Transplant Program at Cedars-Sinai Cancer.  

“We have modified our pretransplant regimens and post-transplant care to minimize toxicity to the patients and give them the best chance for a successful recovery,” Paquette said. “We also are careful to select stem cell donors who can provide the best-quality stem cell and immune cell recovery.”

An allogeneic transplant uses stem cells from a donor, rather than the patient’s own cells, and Paquette said the approaches to these transplants are specific to each institution.

Along with a uniform approach to pretransplant therapy, Chute and Paquette attributed Cedars-Sinai’s top ranking to the frequent use of younger half-matched donors—often a child or grandchild of the patient—to get patients to transplant more quickly.

“In addition to that, there is no replacement for the people who take care of the patients, from the transplant coordinators to the physicians, nurses and advanced practice providers,” Chute said. “The dedication of our team provides that crucial element that yields the best possible results for our patients.”

Chute and Paquette are currently exploring stem cell transplant for patients who would once have been thought “too old” for the procedure.

“Age 75 used to be the upper limit, but that was arbitrary,” Paquette said. “We have transplanted several patients over age 75 and all are doing well so far. We are hoping to learn more about the biology of transplant via these patients, to learn about the pluses and minuses of doing transplants in patients this age. We want to learn not only how to extend their survival but also how to maximize their quality of life.”

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.

Whitson, a biochemist with more than 38 years of space and science experience at NASA, is currently vice president of Human Spaceflight for Axiom Space, the only company with human spaceflight experience on board the International Space Station. She has flown on two Axiom Space commercial astronaut missions in addition to her three NASA long-duration spaceflights.  

Whitson sat down for a “fireside chat” with Arun Sharma, PhD, director of the Cedars-Sinai Center for Space Medicine Research.

Here is an excerpt from their conversation:

Arun Sharma: What are you most excited about, sciencewise, for the next generation of Axiom Space missions?

Peggy Whitson: Part of the reason I was excited to join Axiom Space was the fact that one of their goals is manufacturing in space, and I really wanted to see some of that exciting research take that next step. I think we are going to be able to unlock microgravity, use it as a tool for expanding our capabilities and then bring that capability back to Earth.

What capabilities do you think are critical for the next generation of life science in space?

I think the most important thing is having the capability to analyze and assess on board what's happening, get the data to the ground quickly and have it already processed using orbital data centers. Orbital data centers and data architecture will allow us to do iterative science and process and analyze information in real time on board. I think that will be game changing because it will allow us to quickly take advantage of new ideas that come out of the data.

When it comes to designing experiments for research in space, what should investigators consider?

The biggest thing from a safety perspective is containment. We must be able to protect the crew. And in some cases, we're protecting what we're working on from the crew. Sometimes creating this containment can take away from the ease with which we can do investigations. So I think the right balance needs to be assessed for each investigation.

Another thing to consider is that in the past we thought we had to make everything special for space. But we found a lot of things just off the shelf will work. So take the simplest route first, and try and use as much as possible off the shelf. It costs a lot less than it does to start from scratch and develop all new hardware.

Space is going to become more accessible. So we will have a chance to learn not just how selected astronauts respond to space, but how an everyday person responds to this unique situation. Talk to us about the concept of space for everybody, and what you and Axiom Space are doing to support that vision.

One of the investigations we did on our Axiom Mission 4 (Ax-4) was called Suite Ride, and it looked at insulin response in microgravity. We studied off-the-shelf techniques for monitoring glucose, and tested stability for the insulin on board and injection techniques— demonstrating that diabetes tools operate accurately in space. That's one specific example of how we are looking at opening up access to space.

What do you see as the role of a major academic medical center like Cedars-Sinai in the space ecosystem?

Space offers some unique opportunities, and organizations like Cedars-Sinai have the capability of taking that to the next level by enabling in-space biomanufacturing of advanced materials that we cannot make on Earth to benefit patients everywhere. This research in microgravity will provide the science community the opportunity to develop disease models, helping us better understand diseases to make new drugs and drug therapies for patients. This is an important role that Cedars-Sinai plays in opening up space to other organizations and researchers by just showing them what's possible from a medical perspective.

Do you have advice for students and other trainees who might ultimately pursue careers in space medicine?

Adaptability is important. And I think collaboration is incredibly important when you're working in space. You have to be able to trust people that you're working with. You have to be able to communicate effectively.

I applied to be an astronaut for over 10 years and was rejected until the 10th year. But those 10 years were some of the most valuable because of the experience I gained. It doesn't have to be a straight line to get where you want to go if you are pursuing your goals. Take advantage of the experiences that you have and learn from them. Don't be afraid of failing. You learn from that, and then you make the next run better.

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.

There are currently three types of NAMS: organoids, organ-on-chip technology, and computational, or “in silico,” models.

In an editorial published this fall in the journal Cell Stem Cell, Svendsen discussed the promise and challenges surrounding these methods. He shared some of his thoughts with the Cedars-Sinai Newsroom.

How do the various new approaches work?

Organoids are small bundles of human cells that can mimic some of the function of complete organs.  While they can be generated from some adult human organs such as the gut, these adult organoids often have limited potential for cultivation and replication.  Instead we grow organoids from induced pluripotent stem cells, or iPSCs, which are mature adult human cells that have been reprogrammed into a state where they are immortal, can be replicated indefinitely and can become almost any cell type.

In organ-on-chip models, iPSC-derived organ-specific cells are grown in specially designed chips that mimic fluid flow in the body and replicate conditions cells would experience in an actual organ. In some cases, investigators are linking different types of organ chips—brain, heart, liver—as a way to replicate a complete human system.

With in silico models, AI tools are applied to large databases of human and animal data. These tools allow us to forecast how a drug works or whether it's toxic, based on data from similar drugs that have already undergone animal or human testing.

Why do we use animals, particularly mice, for medical research?

Mice and other animals provide us with a living physiological system with organs and circulation, which is something we haven’t been able to fully replicate in a laboratory dish. They also breed and age quickly, and we have learned to genetically engineer them to mimic many human diseases and conditions.

What is the downside to mice as a stand-in for humans?

Mouse biology and human biology are different in some important ways, including at the molecular level. In one recent case, we were studying a rare disease in children that hinges on a missing gene. When we attempted to create mice with this same disease by “knocking out” that gene—nothing happened. The mice did not develop the disease. It turns out that mice have another gene with very similar functions that is missing in humans. There are millions of genetic differences between mice and humans, and the smallest one can make a huge difference.

Which of the alternative approaches is most developed?

In silico is probably farthest ahead because AI is moving so quickly and we have so much data. Investigators who want to test a new drug can apply AI tools and plug the drug into large publicly available databases to learn how cells might react to that drug. And investigators who have discovered a genetic pathway that is potentially involved in a disease can plug the changes they observed into these databases to determine which drugs might reverse those changes.

Are we ready to make the leap from animal studies to these new scientific methods?

We are entering a transition period where these new technologies are starting to be used to enable new drug development.  These technologies are very, very new and there are only a few examples of where they have been successfully used as an alternative to laboratory animal research.  However,  with many exciting studies on the way, this is set to change in the near future. Stay tuned!

What should we do in the meantime?

Right now, combining some of these new methods with animal models is the best option. A laboratory animal is a complete living specimen. An organoid or organ chip offers actual human biology. And combining AI technology, animal models and organoids to test the same theory about how an organ works, how it goes wrong or how it may react to a new drug will ultimately be incredibly powerful. If all three approaches agree, you have a much greater chance of discovering something important for human health.  

Simultaneously, we will continue to study and test whether the new methods can provide more accurate information about human biology than laboratory animals can. I believe they eventually will, because we're constantly refining and improving NAMS technology. Ultimately, this will also provide a way to tailor our treatments to individuals as we can generate their organoids or organ chips, discover successful drug interactions, and then administer that drug to the same patient.  

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.

Health Risks of Prostate Cancer Therapy Are Similar Across Races

Prostate cancer patients of all racial groups face roughly the same excess risk of developing heart and bone problems when they are treated with androgen deprivation therapy, according to a study led by Cedars-Sinai. The findings, published in JAMA Network Open, support a uniform approach to counseling and monitoring these patients.

Roughly 1 in 8 men will be diagnosed with prostate cancer during their lifetime, according to the American Cancer Society. Androgen deprivation therapy, which blocks the production or action of male hormones that drive prostate cancer, is widely used to treat cancers that have spread outside the prostate.

“While androgen deprivation is an important tool for fighting prostate cancer, numerous studies have found that it also raises the risk of developing bone fractures, osteoporosis, heart attacks, strokes, coronary heart disease, congestive heart failure and peripheral vascular disease,” said Nadine A. Friedrich, MD, a postdoctoral scientist in the Department of Urology at Cedars-Sinai and corresponding author of the study. “We wanted to learn whether these excess risks from androgen deprivation vary by race.”

Investigators reviewed the electronic health records of more than 790,000 patients in the nationwide Veterans Affairs Health Care System who were diagnosed with prostate cancer from 2001 to 2021. The data showed that androgen deprivation therapy was associated with increased cardiovascular and bone risks across all racial groups. There were differences in certain risks between Black and white patients, but they were small.

“The clinical relevance of these slight variations is unclear,” said Stephen J. Freedland, MD, professor of Urology at Cedars-Sinai, staff physician at the Durham VA Medical Center, and study senior author. “Overall, these findings underscore the importance of monitoring all prostate cancer patients undergoing androgen deprivation therapy, regardless of race.”

Additional Cedars-Sinai authors include Kiranbir Josan, MD; and Nicholas P. Tatonetti, PhD

Other authors include Jessica L. Janes, MA; Joshua Parrish, BS; and Amanda M. De Hoedt, MS.

Funding: This research received funding from Sumitomo Pharma America, Inc, and Pfizer, Inc. Dr. Friedrich was funded by National Institutes of Health grant T32 HL11627.

Disclosures: Dr. Freedland reported receiving personal fees from Astellas, Bayer, Pfizer, Sanofi, Merck, AstraZeneca, Eli Lilly, Novartis, Janssen, and Tolmar outside the submitted work.

Cedars-Sinai Neuroscience Study Earns ‘Buzziest Paper’ Honor

Neuroscience news outlet The Transmitter has named a study published in Nature and led by Ueli Rutishauser, PhD, professor and Board of Governors Chair in Neurosciences at Cedars-Sinai, as among “The Buzziest Neuroscience Papers of 2023, 2024.”

The paper, titled “Abstract Representations Emerge in Human Hippocampal Neurons During Inference," illuminated the processes of abstraction and inference. Abstraction is the learning of new knowledge from experience, while inference is the use of this knowledge to make decisions in situations we have never been in. The study found that when people successfully use inference to adapt to new situations, groups of neurons in the hippocampus represent information in an abstract format, a type of coordinated firing of neurons that becomes visible with new tools that make such neural geometries visible.

The Transmitter list, published as part of the publication’s year-end special report on the state of neuroscience, highlights innovative and impactful neuroscience research. The paper’s inclusion underscores its significance in advancing scientific understanding of how the human brain works.

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.

Addison, quien fumó en el pasado, fue referida a una prueba de detección de cáncer de pulmón por su médico de atención primaria porque cumplía con los criterios de detección. Las guías recomiendan realizar estas pruebas a personas entre 50 y 80 años que actualmente fuman o que han fumado el equivalente a una cajetilla diaria durante 20 años o más.

“La atención de esta paciente estuvo guiada desde la detección hasta el diagnóstico por nuestra excelente enfermera practicante, Deborah Gregory”, dijo Sara Ghandehari, MD, directora médica del Programa de Detección de Cáncer de Pulmón en Cedars-Sinai Cancer. “Deborah recopiló las recomendaciones de nuestro equipo multidisciplinario e incluso ayudó a la paciente a superar obstáculos con el seguro para mantener su tratamiento en curso, simplificando el proceso y garantizando un acceso rápido a la atención de seguimiento. Para las personas con mayor riesgo de desarrollar cáncer de pulmón, la detección y el diagnóstico temprano pueden salvar vidas”.

Eso es exactamente lo que ocurrió con Addison. Hoy, está libre de cáncer gracias a la detección temprana y al tratamiento recibido en Cedars-Sinai Cancer.

El proceso de detección incluye una tomografía computarizada de dosis baja, no invasiva, que puede identificar cáncer o nódulos precancerosos dentro de los pulmones. Addison se había estado realizando estas pruebas desde 2021, y en su estudio de 2024 se detectó un cambio en un nódulo previamente identificado en el lóbulo medio de su pulmón derecho.

“El nódulo medía 11 milímetros, lo cual es bastante pequeño”, explicó Christopher Lee, MD, radiólogo y director de imagenología del Programa de Detección de Cáncer de Pulmón, quien interpretó los estudios de Addison. “Un nódulo de este tamaño nunca se detectaría sin una tomografía, ya que no causa síntomas hasta que crece mucho más. Eso es precisamente lo que buscamos con la detección: cánceres en etapa temprana que son potencialmente curables”.

Después de que una biopsia confirmó que el nódulo era canceroso, Addison conoció Andrew Brownlee, MD, cirujano torácico y profesor asistente de Cirugía.

“Me dijo que mi cáncer estaba en una etapa temprana y en el mejor lugar posible”, comentó Addison. “Me explicó que removería ese lóbulo y que el cáncer desaparecería. No tuve que recibir quimioterapia ni radiación. Solo necesito una tomografía cada seis meses durante los próximos dos años, y eso es todo”.

Tras una serie de estudios y preparación, su cirugía fue programada para el 17 de febrero. Debido a que el tumor era muy pequeño y estaba en una etapa temprana, pudo someterse a un procedimiento robótico mínimamente invasivo, conocido como cirugía de “ojo de cerradura”.

“La cirugía de cáncer de pulmón ha avanzado enormemente en las últimas décadas, y uno de esos avances es el uso de procedimientos mínimamente invasivos”, dijo Brownlee. “Realizamos la mayoría de nuestras cirugías de cáncer de pulmón utilizando la plataforma robótica. Los pacientes obtienen los mismos resultados, pero con una recuperación más rápida y sencilla: menos tiempo en el hospital, menos molestias postoperatorias y un regreso más rápido a su vida diaria con un impacto mínimo en la respiración”.

Brownlee explicó que la parte del pulmón de Addison que fue removida —el lóbulo medio derecho— solo participa en aproximadamente el 5% al 10% de la función pulmonar total, por lo que las áreas restantes pueden compensar la pérdida.

“Todos comenzamos con más capacidad pulmonar de la que realmente necesitamos”, dijo. “Cuando se extrae un lóbulo, los demás pueden compensar”.

Después de solo dos días en el hospital, Addison pudo regresar a casa.

“La detección temprana y los tratamientos de vanguardia son sellos distintivos de la atención al paciente en Cedars-Sinai Cancer”, afirmó Robert Figlin, MD, director interino de Cedars-Sinai Cancer. “Estamos comprometidos a lograr los mejores resultados posibles en cada etapa”.

Madre de cuatro hijos y abuela de tres, Addison aconseja a todas las personas que cumplen con los criterios que se realicen la prueba de detección de cáncer de pulmón.

“Es muy importante”, dijo, “especialmente si fumas o fumaste. Si no hubiera sido por la detección, mi cáncer no se habría identificado a tiempo”.

“El cáncer es una palabra que da miedo”, añadió Addison, cuya madre falleció por cáncer de mama y cuyo padre murió de cáncer de colon. “Nadie quiere escuchar esa palabra. Pero mi filosofía de vida es que Dios no pone nada en mi camino sin tener ya la solución. Así que acudí a mis citas médicas, me hice mis radiografías y análisis de sangre, y luego tuve mi cirugía. Aquí estoy, libre de cáncer. No necesito radiación ni quimioterapia, y estoy bien. Puedo seguir adelante y vivir mi vida”.

Lea más en el Blog de Cedars-Sinai: Aclarando el Aire—Respuestas a Tus Preguntas Sobre la Detección del Cáncer de Pulmón

“Astrocytes are critical responders to disease and disorders of the central nervous system—the brain and spinal cord,” said neuroscientist Joshua Burda, PhD, assistant professor of Biomedical Sciences and Neurology at Cedars-Sinai and senior author of the study. “We discovered that astrocytes far from the site of an injury actually help drive spinal cord repair. Our research also uncovered a mechanism used by these unique astrocytes to signal the immune system to clean up debris resulting from the injury, which is a critical step in the tissue-healing process.”

The investigators dubbed these astrocytes “lesion-remote astrocytes,” or LRAs, and identified several distinct LRA subtypes. Their study describes for the first time how one LRA subtype remotely senses and responds to tissue injury.

The spinal cord is a bundle of nerve tissue that runs from the brain down the back. At its center is gray matter, which contains the bodies of nerve cells and support cells called astrocytes. Surrounding it is white matter, made up of astrocytes and long nerve fibers that stretch up and down the cord to send signals between the brain and the rest of the body. Astrocytes help keep the nervous system healthy and ensure that these signals flow smoothly.

Spinal cord injuries damage nerve fibers, paralyzing parts of the body and disrupting sensory input such as touch and temperature. The severed fibers die off and become debris. In most other types of tissue in the body, inflammation takes place only at the site of injury. But because of the length of nerve fibers in the spinal cord, damage and inflammation extend far beyond the injury site.  

Investigators looked at laboratory mice with spinal cord injury and found that LRAs play an important role in supporting nervous system repair. They saw strong evidence of the same mechanism in tissue samples from human patients with spinal cord injury.

The Burda Lab identified one LRA subtype that sends out a protein called CCN1 to signal to immune cells called microglia.

“One function of microglia is to serve as chief garbage collectors in the central nervous system,” Burda said. “After tissue damage, they eat up pieces of nerve fiber debris—which are very fatty and can cause them to get a kind of indigestion. Our experiments showed that astrocyte CCN1 signals the microglia to change their metabolism so they can better digest all that fat.”

Burda said this efficient debris clearing might have a role in the spontaneous recovery found in many patients with spinal cord injury. In the absence of the astrocyte-derived CCN1 protein, the investigators found that recovery is drastically impaired.

“If we remove astrocyte CCN1, the microglia eat, but they don't digest. They call in more microglia, which also eat but don't digest,” Burda said. “Big clusters of debris-filled microglia form, heightening inflammation up and down the spinal cord. And when that happens, the tissue doesn’t repair as well.”

When investigators looked at spinal cord tissue from human patients with multiple sclerosis, they found the same mechanism at work, Burda said. He added that these fundamental principles of tissue repair likely apply to any sort of injury of the brain or spinal cord.

“The role of astrocytes in central nervous system healing is remarkably understudied,” said David Underhill, PhD, chair of the Department of Biomedical Sciences. “This work strongly suggests that lesion-remote astrocytes offer a viable path for limiting chronic inflammation, enhancing functionally meaningful regeneration, and promoting neurological recovery after brain and spinal cord injury and in disease.”

Burda is now leading efforts to harness this CCN1 mechanism in spinal cord healing and to further investigate the role of astrocyte CCN1 in inflammatory neurodegenerative disease and in aging.  

Additional Cedars-Sinai authors include Sarah McCallum, Keshav B. Suresh, Timothy S. Islam, Manish K. Tripathi, Ann W. Saustad, Oksana Shelest, Aditya Patil, David Lee, Brandon Kwon, Katherine Leitholf, Inga Yenokian, Sophia E. Shaka, Jasmine Plummer, Vinicius F. Calsavara, and Simon R.V. Knott.

Other authors include Connor H. Beveridge, Palak Manchandra, Caitlin E. Randolph, Gordon P. Meares, Ranjan Dutta, Riki Kawaguchi, and Gaurav Chopra.

Funding: This work was supported by: the US National Institutes of Health (NIH) 5R01NS128094, R00NS105915, K99NS105915 (to J.E.B.), F31NS129372 (to K.S.), K99AG084864 (S.M.) R35 NS097303 and R01 NS123532 (RD), R01MH128866, U18TR004146, P30 CA023168 and ASPIRE Challenge and Reduction-to-Practice award (to G.C.); the Paralyzed Veterans Research Foundation of America (to J.E.B.); Wings for Life (to J.E.B.); Cedars-Sinai Center for Neuroscience and Medicine Postdoctoral Fellowship (to S.M.); American Academy of Neurology Neuroscience Research Fellowship (to S.M.); California Institute for Regenerative Medicine Postdoctoral Scholarship (to S.M.); The United States Department of Defense USAMRAA award W81XWH2010665 through the Peer Reviewed Alzheimer’s Research Program (to G.C.); The Arnold O. Beckman Postdoctoral Fellowship (to C.E.R.); The Purdue University Center for Cancer Research funded by NIH grant P30 CA023168 is also acknowledged.

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.

AI Framework Speeds Up Brain Neuron Modeling

Cedars-Sinai investigators worked with a multi-institutional team to develop a new artificial intelligence framework that can accurately, quickly and efficiently create virtual models of brain neurons. The achievement could accelerate discoveries in brain function research and ultimately lead to better treatments for brain disorders.

The study’s findings were presented at the 39th Conference on Neural Information Processing Systems in San Diego.

“Computational modeling of brain neurons has become an important tool for studying their activity and interactions,” said co-author Costas Anastassiou, PhD, associate professor of Neurology, Neurosurgery and Biomedical Sciences at Cedars-Sinai. “But traditional models are hindered by limitations including the cost of computer resources, data availability and cumbersome handling. Our new framework tackles this problem by operating at speeds thousands of times faster than existing methods while remaining so biologically accurate that it can capture the variability of actual brain neurons, unlike current approaches. The framework can also generate an unlimited number of virtual neurons, better reflecting the diversity and variability of actual biological neurons.”

Anastassiou added that the framework opens a pathway toward modeling larger-scale brain circuits that could improve understanding of the relationships between gene expression, electrical activity and networking in neurons. The investigators named their invention NOBLE, for Neural Operator with Biologically-informed Latent Embeddings.

“I am very happy to see this interdisciplinary and inter-institutional collaboration,” said Anima Anandkumar, PhD, Bren Professor of Computing and Mathematical Sciences at Caltech and a co-author of the study. “Neural operators are designed to capture the complex dynamics seen in biological neurons, and this is the first large-scale AI framework validated with experimental human cortex data.”

The additional Cedars-Sinai author is Philip H. Wong.

Other authors include Luca Ghafourpour, Valentin Duruisseaux, and Bahareh Tolooshams.

Funding: A.A. is supported by the Bren Endowed Chair, ONR (MURI grant N00014-23-1-2654), and the AI2050 Senior Fellow program at Schmidt Sciences. C.A.A. is supported by the National Institutes of Health R01 - NS120300 and R01 - NS130126. P.H.W. is supported by the National Institutes of Health R01 - NS130126.

Liver Cancer Prevention, Treatment Efforts Are Working

Prevention and treatment advances are reducing the number of new liver cancer patients and narrowing survival gaps among racial groups, a Cedars-Sinai Cancer study published in the journal Clinical Gastroenterology and Hepatology reports.

“We found that liver cancer rates in the U.S. have begun to decline after many years of increase, and deaths from liver cancer have stabilized,” said Ju Dong Yang, MD, medical director of the Liver Cancer Program at Cedars-Sinai and senior author of the study. “Younger patients and those with advanced disease are living longer, partly due to new therapies. And differences in survival rates between Black and white patients have nearly disappeared, suggesting that fairer access to care and treatment advances are helping reduce longstanding racial disparities.”

Investigators looked at data from the National Cancer Institute’s Surveillance, Epidemiology, and End Results cancer registry on newly diagnosed liver cancer cases, tumor stage at diagnosis, treatment trends, and survival rates in the U.S. over the past two decades. Despite declining liver cancer rates and improved overall survival, they found that early detection and curative treatment decreased during the COVID-19 pandemic. Investigators suggest this highlights the importance of strengthening screening and care access during healthcare disruptions.

Additional Cedars-Sinai authors include Yi-Te Lee, Hyun-seok Kim, Alexander Kuo, Walid S. Ayoub, Hirsh D. Trivedi, Yun Wang, Aarshi Vipani, Paul Martin, and Cristina R. Ferrone.

Other authors include Jasmine J. Wang, Pojsakorn Danpanichkul, and Amit G. Singal.

Funding: Dr. Singal’s research is funded by National Institutes of Health R01CA256977 and R01 MD012565. Dr. Yang’s research is supported by National Institutes of Health K08CA259534; R21CA280444.

Disclosures: Dr. Yang provides a consulting service for AstraZeneca, Eisai, Exact Sciences, Exelixis, Fujifilm Medical Sciences, Merck, and Gilead Sciences.

New AI Tool Improves Heart Test Evaluation

A new AI tool can rapidly evaluate data from echocardiography, an imaging test commonly used to diagnose heart disease, according to new research led by Cedars-Sinai. The study, published in JACC, found the tool could speed up the testing process and yield more uniform results.

The AI system automatically takes 18 different measurements during echocardiography, which uses high-frequency sound waves to create moving pictures of the heart and evaluate blood flow. The procedure is used to assess signs and symptoms of heart failure, atherosclerosis, cardiomyopathy and other conditions.

“Our AI tool demonstrated accuracy and precision comparable to that of expert sonographers from two medical institutions,” said David Ouyang, MD, assistant professor in the Department of Cardiology in the Smidt Heart Institute at Cedars-Sinai and corresponding author of the study. “One of the primary benefits of automation is that it reduces examination time and produces more consistent readings.”

Ouyang added that more testing is needed before the tool is used for patients.

Additional Cedars-Sinai authors include Yuki Sahashi, Victoria Yuan, Matthew Christensen, Milos Vukadinovic and Christina Binder-Rodriguez.

Additional authors include Hirotaka Ieki, Justin Rhee, James Y. Zou, Bryan He and Paul Cheng.

Funding: This work was funded by National Institutes of Health, National Heart, Lung, and Blood Institute grants R00HL157421, R01HL173526, and R01HL173487.

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.

Addison, who previously smoked, was referred to the Cedars-Sinai Lung Cancer Screening Program by her primary care physician because Addison met screening guidelines. Those guidelines recommend screening those 50-80 years old who currently smoke or have smoked the equivalent of one pack of cigarettes a day for 20 years or more.

“Once Addison entered our Lung Cancer Screening Program, her care was guided by our nurse practitioner, Deborah Gregory, who ensured she felt informed and supported from screening through diagnosis,” said Sara Ghandehari, MD, medical director of the Lung Cancer Screening Program at Cedars-Sinai Cancer. “Deborah presented her case to our multidisciplinary team, delivered timely expert recommendations, and navigated insurance hurdles to keep her care on track. The Lung cancer Screening Program facilitates the screening process and provides fast access to diagnosis and follow-up care.  For people at increased risk for developing lung cancer, screening and early detection can save lives.”

That’s exactly what happened to Addison. Today, Addison is cancer-free, following screening, early detection and treatment at Cedars-Sinai Cancer.

The screening process involves a noninvasive, low-dose CT scan that can detect cancer or precancerous nodules inside the lungs. Addison had been undergoing screenings since 2021, and her screening in 2024 detected a change in a previously identified nodule in the middle lobe of her right lung.

“The nodule measured 11 millimeters, which is quite small,” said Christopher Lee, MD, radiologist and imaging director of the Lung Cancer Screening Program, who read Addison’s scans. “A nodule of this size would never be noticed without a CT scan since they do not cause symptoms until they become much larger. That's basically what we're trying to catch with screening: early-stage cancers that are potentially curable.”

After a biopsy confirmed the nodule was cancerous, Addison met Andrew Brownlee, MD, thoracic surgeon and assistant professor of Surgery.

“He told me that my cancer was at an early stage and in the best place that I could have it,” Addison said. “He said he would remove that lobe and my cancer would be gone. So I didn’t have to have chemotherapy, I didn’t have to have radiation. I have to have a CT scan every six months for the next two years, but that is all.”

After a series of tests and other preparation, she was scheduled for surgery Feb. 17. Because her tumor was so small and at such an early stage, she was able to have a robotic “keyhole” procedure to remove it.

“Lung cancer surgery has made tremendous advances in recent decades, and one of those is the use of minimally invasive procedures,” Brownlee said. “We perform the lion's share of lung cancer surgeries using the robotic platform. Patients have the same outcomes, but with a faster, easier recovery—less time in the hospital, less postoperative discomfort and a faster return to their everyday life with minimal impact on their breathing.”

Brownlee said that the area of Addison’s lung that was removed, the middle portion on the right side, participates in only about 5% to 10% of lung function, so the remaining portions of her lungs can make up for the missing portion.

“We all start out with more lung capacity than we need,” Brownlee said. “So when we remove one lobe, the other lobes can compensate.”

After just two days in the hospital, Addison was able to go home.

“Early detection and leading-edge treatment are hallmarks of patient care at Cedars-Sinai Cancer,” said Robert Figlin, MD, interim director of Cedars-Sinai Cancer. “We are dedicated to producing the best possible outcomes at every turn.”

The mother of four and grandmother of three advises everyone who is eligible to seek out lung cancer screening.

“It is very important,” she said, “especially if you are a smoker or have been a smoker. If it hadn’t been for my screening, my cancer wouldn’t have been caught in time.

“Cancer is a scary word,” said Addison, whose mother died from breast cancer and whose father died from colon cancer. “Nobody wants to hear that word. But my philosophy of life is that God is not going to put anything on my plate that he does not already have the solution to. So, I made my doctor's appointments, went to get my X-rays and blood work, and then I had my surgery, and here I am cancer-free. I do not need radiation, do not need chemotherapy, and I'm fine. I can go ahead and live my life.”

Read More on the Cedars-Sinai Blog: Clearing the Air—Your Lung Cancer Screening Questions Answered

Cedars-Sinai experts are available to discuss the complex neurodegenerative disorder that caused civil rights leader the Rev. Jesse Jackson to be hospitalized.

The rare movement disorder called progressive supranuclear palsy (PSP) affects parts of the brain that control the body’s ability to walk and coordinate movement. Cedars-Sinai is a designated CurePSP Center of Care and has multidisciplinary clinics for patients with PSP and other movement disorders.  

Patients’ brains contain abnormal clumps of tau protein, which has also been implicated in Alzheimer’s disease. PSP patients often notice they have difficulty in moving their eyes. Other symptoms include unexplained falls and difficulty with impulsivity and decision-making.

“PSP is similar to Parkinson’s disease but is rarer,” said Yvette Bordelon, MD, PhD, who is part of the Movement Disorders Division in the Cedars-Sinai Department of Neurology, and is co-director of the Cedars-Sinai CurePSP Center of Care.

Cedars-Sinai experts available for interviews:

• Yvette Bordelon, MD, PhD, co-director of the Cedars-Sinai CurePSP Center of Care.
• Sarah Kremen, MD, director of the Neurobehavior Program at Cedars-Sinai and co-director of the Cedars-Sinai CurePSP Center of Care.
• Michele Tagliati, MD, vice chair of the Department of Neurology and director of the Movement Disorders Program at Cedars-Sinai.

To arrange interviews, contact Christina Elston at 626-298-0702 or christina.elston@cshs.org.

The study, published in the journal Liver Cancer, found that these patients had overall survival rates that were 85% higher than patients who received immunotherapy alone.

“The data we reviewed showed that patients who received follow-up transplants or tumor removal after immunotherapy reduced the size of their tumors lived much longer than patients who just remained on immunotherapy,” said Ju Dong Yang, MD, medical director of the Liver Cancer Program at Cedars-Sinai and senior author of the study.

Liver cancer is rarely detected in the earliest stages, when tumors are small enough that a transplant or removal is possible. In advanced liver cancer, immunotherapy—medications that harness the power of a patient’s immune system—can shrink tumors but not cure the disease.

Previous research, also led by Cedars-Sinai, found that liver transplant or tumor removal is possible after immunotherapy shrinks a tumor to “downstage” the cancer. In this new study investigators wanted to see how well patients treated with these follow-up procedures fared.

They reviewed data on more than 4,300 patients with advanced liver cancer from the National Cancer Database, which contains more than 70% of all newly diagnosed cancer cases in the U.S.

Despite the higher overall survival rates after follow-up procedures, only about 3% of patients on immunotherapy went on to receive transplants or tumor removal. Most of those patients were treated at academic medical centers like Cedars-Sinai, the investigators found.

“Performing liver transplant following immunotherapy isn’t yet common practice,” Yang said. “This is unfortunate, as patients with advanced liver cancer often die without such treatment—even if their cancer is under control—because they also have other liver ailments. A transplant leaves the patient with a healthy liver.”

Yang plans to further make his case for more aggressive treatment for these patients through a new study that will launch in the coming months. Investigators will enroll patients who receive immunotherapy followed by liver transplants and will record their outcomes.

“When our physician-scientists create studies based on patient needs and then apply their findings to patient care, it improves outcomes for everyone we serve and for patients around the world,” said Robert Figlin, MD, interim director of Cedars-Sinai Cancer. “As an academic medical center, that is our mission.”

Additional Cedars-Sinai authors include Gwang Hyeon Choi, Hyun-Seok Kim, Michael Luu, Alexander Kuo, Walid S. Ayoub, Hirsh Trivedi, Yun Wang, Aarshi Vipani, Pin-Jung Chen, Steven A. Miles, Emily A. Kaymen, Andrew Hendifar, Tsuyoshi Todo, Todd V. Brennan, Georgios Voidonikolas, Steven A. Wisel, Justin Steggerda, Cristina Ferrone, Kambiz Kosari and Nicholas Nissen.

Other authors include Neehar D. Parikh and Amit G. Singal.

Funding: Dr. Singal’s research is supported by NCI R01 MD012565 and R01 CA256977. Dr. Yang’s research is supported by NCI K08CA259534.

Conflict of interest: Ju Dong Yang provides consulting service for AstraZeneca, Eisai, Exact Sciences, Exelixis, and Fujifilm Medical Sciences.

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.

Preclinical Study: Protecting Against Diabetic Corneal Disease

The medical journal Diabetologia recently published a Cedars-Sinai study that helps explain why half of diabetes patients experience deterioration of the cornea, the transparent dome-shaped outer layer of the eye that provides protection and focuses incoming light. The findings point to a potential target for therapies to protect vision in these patients.

Investigators performed experiments comparing diabetic versus nondiabetic human corneal cells to explain the molecular changes that diabetes patients experience. Diabetic corneal disease can lead to delayed wound healing and loss of vision.

“Our findings highlight the major role of a molecule called microRNA-10b in the oxidative stress characteristic of diabetic corneal disease and the damage it causes to cells,” said Mehrnoosh Ghiam, PhD, associate professor of Biomedical Sciences, research scientist in the Board of Governors Regenerative Medicine Institute and senior author of the study. “Inhibiting this molecule restored the cornea’s defenses against oxidative stress and cell damage and allowed the outermost layer of cells to be maintained and renewed.”

Additional Cedars-Sinai authors include Daxian Zha, Joshua Gamez, Shaghaiegh M. Ebrahimi, Yizhou Wang, Nagendra Verma, Adam J Poe, Seok White, Ruchi Shah, Andrei A. Kramerov, Chintda Santiskulvong, Aleksandr B. Stotland, Zhiping P. Wang, Jennifer E. Van Eyk, and Alexander V. Ljubimov.

Other authors include Onkar B. Sawant.

Funding: This work was supported by grants from the National Institutes of Health R01 EY025377 (MS); R01EY029829 (MS); R01EY031377 (AVL), R01EY013431 (AVL); the California Institute for Regenerative Medicine (CIRM EDUC4-12751); and funding from the Board of Governors Regenerative Medicine Institute (MS).

Cedars-Sinai Study Highlights AI Limits in Heart Care

There are limits in applying AI to images of the heart, a new study from the Smidt Heart Institute at Cedars-Sinai reveals. The findings were published in the Journal of the American Society of Echocardiography.

Investigators trained multiple artificial intelligence models to read images from echocardiograms, a type of ultrasound test that evaluates the structure and function of the heart. Their goal was to determine whether AI could use these images to calculate measurements like inflammation and scarring that are normally obtained through another, more costly test called cardiac magnetic resonance imaging (CMRI). By examining findings from1,453 patients who had undergone both tests, they found the AI models could not accomplish this task.

“As compared to echocardiograms, cardiac MRI machines are expensive and not available for many patients, especially those in rural areas, so we had hoped that AI could reduce the need for it,” said Alan Kwan, MD, assistant professor in the Department of Cardiology in the Smidt Heart Institute at Cedars-Sinai and co-senior author of the study. “Our results showed the limited powers of AI in this area.”

Other Cedars-Sinai investigators include: Yuki Sahashi, MD, MSc; Milos Vukadinovic, BS; Grant Duffy, BS; Debiao Li, PhD; Susan Cheng, MD, MMSc, MPH; Daniel S. Berman, MD; and David Ouyang, MD (co-senior author).

Acknowledgments: This work was supported in part by grants from the American Heart Association (23CDA1053659), the NIH (KL2TR001882), (75N92020D00021), the NHLBI (R00HL157421), (75N92020D00021, the NBIB through the Medical Imaging and Data Resource Center (MIDRC), Japanese Society of Echocardiography (Foreign research grant), and Japanese Society for the Promotion of Science, Grants-in-Aid for Scientific Research (JSPS-KAKENHI). No funders had a role in the design/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.

Competing interests: ACK reports support from the American Heart Association (AHA; 23CDA1053659) and National Institutes of Health (NIH; KL2TR001882), and consulting fees from InVision Medical Technology. DO reports support from the National Institute of Health (NIH; NHLBI R00HL157421) and Alexion, and consulting or honoraria for lectures from EchoIQ, Ultromics, Pfizer, InVision, the Korean Society of Echo, and the Japanese Society of Echo. YS reports honoraria for consulting from m3.com inc.

Racial Differences and Prostate Cancer Treatment Decisions

Black men choose aggressive prostate cancer treatment—regardless of anticipated life expectancy—more often than Hispanic or Caucasian men, according to new research by Cedars-Sinai investigators published in the journal Prostate Cancer and Prostatic Diseases.

In the study, more than 2,000 men selected to mimic the sociodemographics of the U.S. prostate cancer population were asked to choose between conservative management and aggressive treatment in various prostate cancer diagnosis scenarios. These scenarios required participants to make treatment choices in the setting of different risks of cancer death and side effects, all while considering their anticipated life expectancy. Life expectancy is important because prostate cancer is typically slow-growing, and treatment only benefits men with relatively long life expectancies. Among Hispanic and Caucasian men, lower life expectancy was associated with lower likelihood of choosing aggressive treatment. Black men consistently elected to pursue aggressive treatment regardless of life expectancy. This pattern may put Black men at higher risk for overtreatment.

Timothy J. Daskivich, MD, director of Academic Urologic Oncology for the Department of Urology at Cedars-Sinai and corresponding author of the study, said more research is needed to determine why Black men routinely chose aggressive treatment.

“We have to be aware of cultural differences that may make different groups of patients pursue treatment for different reasons,” Daskivich said. “It’s important to have a holistic view and to understand patients’ motivations for making the decisions they do so that we can provide the best possible care.”

Additional Cedars-Sinai authors include John M. Masterson, Rebecca Gale, Brennan Spiegel and Stephen J. Freedland.

Other authors include Renning Zheng, Michael Luu, Adam Murphy, Yaw A. Nyame and Chad Ritch.

Funding: NIH/NCI K08 CA230155; Open access funding provided by SCELC, Statewide California Electronic Library Consortium.

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 combination therapy, which adds a drug called enzalutamide to commonly prescribed hormone therapy, reduced deaths in patients with recurrent prostate cancer after surgery or radiation for whom other treatments are no longer an option. The trial results were published in The New England Journal of Medicine (NEJM) with simultaneous presentation during the European Society for Medical Oncology Congress (ESMO) Oct. 19 in Berlin.

“After initial treatment, some patients see their prostate cancer come back in an aggressive way and are at risk for their disease to spread quickly,” said Stephen Freedland, MD, director of the Center for Integrated Research in Cancer and Lifestyle at Cedars-Sinai Cancer and co-principal investigator of the study. “Hormone therapy, which is what we’ve been offering patients for 30 years, has not improved survival and neither has anything else. That makes these findings a real game changer.”

The trial included more than 1,000 patients from 244 sites in 17 countries. All the patients were diagnosed with what is known as high-risk biochemically recurrent prostate cancer. Following the patients’ surgery or radiation therapy, the levels of prostate specific antigen, or PSA, in their blood had risen rapidly. PSA is a protein used to detect prostate cancer, and a rapid rise in PSA levels after treatment indicates a patient’s cancer is likely to return and spread—often to the bones or spine.

“We know these patients are at high risk of developing metastatic disease and dying of their cancer unless we offer a meaningful treatment option,” said Freedland, professor of Urology and the Warschaw, Robertson, Law Families Chair in Prostate Cancer.

Patients were randomly selected to receive standard hormone therapy alone, enzalutamide alone, or a combination of the two. After eight years, the risk of death was 40.3% lower in the combination group than in the other two groups, Freedland said.

“This clinical trial, one of many that Cedars-Sinai Cancer has offered to its patients, is an example of the translational work being done by our physician-scientists,” said Robert Figlin, MD, interim director of Cedars-Sinai Cancer. “The result will be improved treatment and better outcomes for patients everywhere.”

Freedland noted that, based on previous results published by the team, enzalutamide is approved by the Food and Drug Administration and listed in National Comprehensive Cancer Network treatment guidelines. These latest results, he said, are likely to strengthen the network’s recommendation and solidify this drug combination as the standard of care for patients with high-risk biochemically recurrent prostate cancer.

“These important findings identify a treatment that prolongs survival in men with aggressive prostate cancer,” said Hyung Kim, MD, a urologic oncologist and chair of the Department of Urology at Cedars-Sinai.  “The latest analysis complements previous studies that found enzalutamide significantly improved survival in other prostate cancer settings, and will change how we take care of our patients.”

Additional authors include Neal D. Shore, M.D.; Murilo de Almeida Luz, M.D.; Ugo De Giorgi, M.D., Ph.D.; Martin Gleave, M.D.; Geoffrey T. Gotto, M.D., M.P.H.; Christopher M. Pieczonka, M.D.; Gabriel P. Haas, M.D.; Choung-Soo Kim, M.D.; Miguel Ramirez-Backhaus, M.D.; Antti Rannikko, M.D., Ph.D.; Matko Kalac, M.D., Ph.D.; Swetha Sridharan, M.B.B.S.; Matt Rosales, Ph.D.; Yiyun Tang, Ph.D.; Ronald F. Tutrone Jr, M.D.; Balaji Venugopal, M.B.B.S., M.D.; Arnauld Villers, M.D., Ph.D.; Henry H. Woo, M.B.B.S., D.Med.Sc.; and Fong Wang, M.D., Ph.D.

Funding: The study was sponsored by Pfizer Inc. and Astellas Pharma Inc., the co‑developers of enzalutamide.

Disclosures: Stephen J. Freedland reports being a consultant to Astellas Pharma Inc., AstraZeneca, Bayer, Eli Lilly, Johnson & Johnson Innovative Medicine (formerly Janssen), Merck, Novartis, Pfizer Inc., Sanofi, Sumitomo Pharma America, Inc. (formerly Myovant Sciences, Inc.), and Tolmar.

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According to the Centers for Disease Control and Prevention, about 10 percent of new breast cancer cases in the U.S. are in women younger than 45.

“We don’t have routine screening recommendations for patients younger than 40, and people aren’t aware that if they have a strong family history, especially in a first-degree relative like a mother, sister or aunt, they should be screened sooner,” said Mary El-Masry, MD, the hematologist-oncologist who led Dade’s care team.

Dade, who received her care from an integrated team at Cedars-Sinai Cancer Beverly Hills, is dancing once again, but treatment for triple-negative breast cancer wasn’t easy. It began with a regimen known as KEYNOTE-522. The protocol included four types of chemotherapy medications to shrink the tumor, plus an immunotherapy drug to help Dade’s immune system do its part in fighting the cancer.

Also there to help were her mother and her partner, Marcus Mack.

“I really just kind of fell into the hands of my care team, knowing that this treatment regimen was going to be extremely rough,” Dade said. “I had moved in with Marcus only three months before I was diagnosed. And then my mom moved in. Who would have thought that my mother and my partner would both be taking care of me.”

Tumors like Dade’s are “negative” for three important receptors—estrogen, progesterone and HER2—that many treatments use to target tumors, making them among the most aggressive and challenging to treat. El-Masry called the protocol Dade received a “breakthrough” in the world of triple-negative breast cancer.

“Mataya has an excellent prognosis,” El-Masry said. “She had a complete clinical response to her treatment. We could see her tumor shrinking.”

Following her chemotherapy and immunotherapy regimen, Dade opted for a double mastectomy with reconstructive surgery. And as a social media influencer, she chose to document her treatment journey.

“This is a message to my future me that I am a baddie and I will get through cancer,” she said to her followers.

For young women like Dade, El-Masry said that it is important to seek out earlier screening if there is family history of cancer—and to be your own advocate.

“If you feel something, bring it to someone’s attention and push to have some imaging done,” El-Masry said. “That could mean a mammogram or, if you are concerned about radiation exposure, an ultrasound. And if imaging isn’t showing anything but you feel a lump, you should ask to have it biopsied so we can be sure it isn’t something we need to be concerned about.”

Several days after her surgery, Dade was able to post the news her friends and family had been waiting for: “I, Mataya Dade, am cancer free.”

With that, she is at work creating a podcast—supported by Mack, a composer and producer—called “You Survived! Now What?” The plan is to offer advice and create a community for other young cancer survivors who are taking their next steps in life—just like Dade and Mack are taking theirs.

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“Organoids are three-dimensional clumps of cells—in this case heart or brain cells,” said Arun Sharma, PhD, director of the Cedars-Sinai Center for Space Medicine Research. “To create them, we reprogram skin or blood cells into stem cells and then turn the stem cells into the heart or brain cells that will form the organoids.”

Organoids, which have thus far only been produced on Earth, are less than 1 millimeter in size and are usually too small to see with the naked eye. But they pack a big scientific punch.

“We can create thousands of these organoids in just weeks, allowing us to model disease and test drugs at a scale we would not be able to achieve otherwise,” said Sharma, also a research scientist in the Board of Governors Regenerative Medicine Institute, Smidt Heart Institute, and Cedars-Sinai Cancer, and associate professor of Biomedical Sciences at Cedars-Sinai.

The cells will travel to space as part of NASA’s SpaceX 33rd commercial resupply services mission to the International Space Station, the sixth mission in which Cedars-Sinai has participated. This is the third mission funded via a NASA In-Space Manufacturing Award in partnership with Axiom Space, a Houston-based company developing space infrastructure. Some firsts from previous missions included the introduction of DNA into stem cells in space, use of off-the-shelf terrestrial lab hardware for space biosciences research, and the production of stem cells in space, Sharma said.

Sharma, a specialist in heart biology, uses organoids to study the effects of cancer therapies on the heart. Heart organoids can also be used to test therapies that might improve heart function, and to study various types of heart disease such as congenital heart defects.  

Clive Svendsen, PhD, executive director of the Board of Governors Regenerative Medicine Institute and a collaborator on the mission, studies brain organoids.

“My lab is focused on the study of neurodegenerative diseases such as ALS, Huntington’s disease and Parkinson’s disease, and we use brain organoids as a tool for modeling these diseases,” Svendsen said. “Creating these organoids in space is potentially a step toward accelerating our work and gaining better understanding of these diseases.”

Sharma said there are potential advantages to growing organoids in space.

“On Earth, gravity compresses these organoids, which are three-dimensional spheres,” Sharma said. “In space, gravity is reduced to almost nothing, what we call microgravity, and we believe that organoids will grow better under these conditions. They might develop new blood vessels that we aren’t able to develop on Earth, organize themselves in unique ways, or maybe even harbor different cell types that we can only develop in microgravity.”

Maedeh Mozneb, PhD, associate director of the Center for Space Medicine Research, and Sharma Lab research associate Madelyn Arzt will travel to Florida to prepare the cells for launch.

The stem cells, obtained from the Allen Institute for Cell Science, will be frozen for the trip to space and will travel aboard a SpaceX rocket in a “plate habitat” created by BioServe Space Technologies in Colorado. Once the cells reach the space station, they will be maintained by astronauts, who will change the nutrients that allow the organoids to grow and photograph the organoids using microscopes, Sharma said.

After approximately one month, the organoids will be sent back to Cedars-Sinai investigators for analysis of their size, shape, genetics and other factors. And despite the tiny size of the organoids, Sharma and his team are dreaming big.

“A dream of mine is to have a lab in space that is parallel with the labs that we have here on Earth,” Sharma said. “That would allow us to create organoids and explore biomedical applications like bioprinting of artificial heart, brain and muscle tissues in space in ways that we may not be able to on Earth.”

Next up, the team will be working on experiments funded through a new grant from the National Institutes of Health to explore using microgravity to model accelerated inflammation and aging in organ chip models of the heart, gut, and brain.

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“Cancer patients are a vulnerable population,” said Jane Figueiredo, PhD, director of Community Health and Population Research at Cedars-Sinai and senior author of the study. “Their immune systems can be weakened by their disease and the treatments they receive, which is why major health organizations recommend that these patients be vaccinated against COVID-19. Our study supports these recommendations. We used real-world data across four major health systems in the U.S. to show that these booster vaccines reduce the risk of hospitalization and severe illness.”

Investigators analyzed data on more than 161,000 patients treated for cancer during 2022 and 2023 at Cedars-Sinai, Kaiser Permanente Northern California, Northwell Health, and the Veterans Health Administration.

The data showed COVID-19 boosters reduced cancer patients’ hospitalizations and ICU admissions by 29% and prevented one hospitalization or ICU admission for every 150-166 boosted patients.

“The reduction in hospitalizations was significant, and the number of patients we needed to treat to see a benefit to the boosters is quite low,” said Figueiredo, who is also program leader of Cancer Prevention and Control at Cedars-Sinai. “This shows a great benefit to our cancer patients and should encourage patients to discuss vaccination with their healthcare providers.”

Figueiredo noted that among their sample, the percentage of patients receiving boosters was quite low. By Jan. 1, 2022, 68% had received a booster. And after updated boosters targeting more than one COVID-19 strain had become available, only 38% of patients had received one.  

“Whether this is due to patient concerns about safety or provider uncertainty about whether to administer a vaccine during treatment is not clear,” Figueiredo said. “What is clear is that we need to advocate strongly for vulnerable groups, including cancer patients, to receive these vaccines.”

Figueiredo noted that the COVID-19 pandemic was the first opportunity for investigators to examine data on mRNA vaccines, and five years later there is still much to learn about the effectiveness of these vaccines in various populations.

“This is the largest study to date of COVID-19 booster effectiveness in cancer patients, a high-risk population of critical importance,” said Robert Figlin, MD, interim director of Cedars-Sinai Cancer. “It adds substantially to our understanding of the effectiveness of COVID-19 vaccines, and we will undertake additional studies as vaccine formulations change and new variants emerge so that we can make recommendations that best protect the health of our patients.”

Figueiredo’s team is preparing to publish vaccine effectiveness data on patients with autoimmune diseases and patients who have undergone solid organ transplants.

“There are several different groups whose immune systems have been affected in different ways, which gives us an opportunity to expand further our understanding of how these vaccines work,” Figueiredo said.

Additional Cedars-Sinai authors include Elham Kazemian, PhD; Karen L. Reckamp, MD; and Akil Merchant, MD.

Additional authors include Jacek Skarbinski, MD; Eric P. Elkin, MPH; Yonah C. Ziemba, MD; Brigid M. Wilson, PhD; Hinnah Siddiqui, MPH; Cheryl B. Schleicher, MS; Crystal A. Hsiao, MPH; Joshua R. Nugent, PhD; James M. Crawford, MD, PhD; David A. Zidar, MD, PhD; and Lawrence H. Kushi, ScD.

Funding: This work was supported by the National Cancer Institute Serological Sciences Network (SeroNet) [U01CA260584 to JS and LHK; U01CA260513 to DZ; 2UG1CA189850-09S1 to YCZ, CBS, JMC; 3U54CA260591-02S3 to JF], the Physician Researcher Program of The Permanente Medical Group Delivery Science and Applied Research Program (JS), and the United States Veteran Administration (COVID19-8900-05 to DZ).

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Calederón Hernández, who goes by the nickname “Gina,” is the 100th patient to receive CAR T-cell therapy at Cedars-Sinai, said Akil Merchant, MD, Lymphoma Program co-director.

“In cancers such as lymphoma, immune cells, which are some of the most powerful anticancer tools that we have, don’t work very well,” said Merchant, who is Calderón Hernández oncologist. “In CAR T-cell therapy we remove those immune cells from the patient, engineer them in the lab to target the cancer cells, then give them back to the patient so they can kill the cancer.”

Since the Cedars-Sinai CAR T program opened in 2020, it has seen rapid, exponential growth, said Justin Darrah, MD, co-director of the Lymphoma Program and director of the CAR T Program.

“Cedars-Sinai is now able to offer this great treatment to many more patients,” Darrah said. “The fact that we have been able to treat 100 patients so far is just an incredible feeling. And the program continues to grow.”

Calderón Hernández, who will turn 60 in August, said her illness began with what she thought was a throat infection.

“I went to the ER in Long Beach. They admitted me and started many tests,” she said. “They removed my tonsils and sent them to pathology. That’s when they said, ‘We’re sorry, but you have lymphoma. You have cancer.’”

When chemotherapy treatment caused Calderón Hernández to lose her hair—for her the most difficult part of treatment—her great nephew Mateo, who is 7, was there to comfort her.

“I was crying in my room,” she said. “He came in and saw me crying. He said, ‘I know why you’re sad, Auntie. It’s because you don’t have hair. But you know what? That haircut doesn’t look bad. You look good, Auntie.’”

Calderón Hernández was cancer free for just under a year and had returned to work as a nanny. But soon she found herself back in the hospital receiving news that her lymphoma had returned.

“Starting over was very hard,” Calderón Hernández said. “The only thing that’s held me up has been God. I thank God for this new chance at life and for the doctors.”

Her oncologist in Long Beach connected Calderón Hernández with the CAR T Program at Cedars-Sinai. This therapy gave Calderón Hernández  an alternative to a bone marrow transplant, which is more difficult on the body, said Darrah, a member of Calderón Hernández's care team.

“CAR T-cell therapy is designed for patients who are having a poor response to other treatment and allows us to cure patients who otherwise were incurable,” Darrah said.

And while Merchant warned Calderón Hernández that CAR T-cell therapy could come with side effects—including memory issues, nausea and dizziness—she said that she didn’t experience those during her seven-day hospital stay.

“After the second day of treatment, I walked 20 minutes around the hospital and took selfies to send my sister,” Calderón Hernández said. She was doing so well she was sent home three days early.

In an active clinical research program, scientists are working to understand which patients are most likely to benefit from existing CAR T-cell therapies and to develop new ones, Merchant said.

“Patients whose cancers may not be treatable with currently approved CAR T-cell therapies could access the next generation of therapies here through clinical trials,” said Robert Figlin, MD, interim director of Cedars-Sinai Cancer. “Some of those options could be more effective than those currently FDA [Food and Drug Administration] approved, and making them available is part of our commitment to pair each patient with the most effective possible treatment.”

He said that most patients who are still in remission nine to 12 months after CAR T treatment are cured, and that is his hope for Calderón Hernández.

“We're going to continue to do scans to look for lymphoma,” Merchant said. “Her scans are negative, and I hope that they stay that way. Fingers crossed for Gina.”

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“Staging helps clinicians answer two questions,” said Allen Ho, MD, professor of Surgery, director of the Head and Neck Cancer Program at Cedars-Sinai and lead author of the study. “The first: How serious is the cancer? The second: What is the best treatment?”

Previous staging guidelines for HPV-positive throat cancer were so broad that as many as 80% of patients were classified as stage 1, with three different possible treatment strategies. Some stage 1 patients were treated with surgery alone, some with surgery plus radiation therapy, and some with surgery and radiation plus chemotherapy.

“The new staging will better inform clinicians and patients about a patient’s prognosis and will minimize inconsistencies in the treatments patients are offered,” Ho said. “Currently, a patient diagnosed as stage 1 might be offered surgery plus radiation and chemotherapy, while another stage 1 patient may be offered surgery alone. The new guidelines will help ensure each patient receives the most appropriate treatment.”

Investigators divided the huge group of stage 1 patients into three separate groups, Ho said. They created new subdivisions of nodal staging, which consider whether cancer has spread to lymph nodes, and paired a more cohesive treatment recommendation with each.

“Perhaps the biggest change in the new staging system is that it takes into account something called extranodal extension, where the cancer has not only spread to the lymph nodes, but has progressed further to destroy the lymph node capsule and spill into the surrounding tissue. Inclusion of this factor is important, because it often changes both prognosis and the recommended treatment following surgery,” said Zachary Zumsteg, MD, professor of Radiation Oncology and Biomedical Sciences at Cedars-Sinai and senior author of the paper. 

Ho noted that cases of HPV-positive throat cancer, caused by the same virus that causes cervical cancer, have outpaced cervical cancer because women are routinely screened for cervical cancer. They are also more likely than men to receive the HPV vaccine, which can prevent both cancer types.

The new guidelines were developed by an international committee led by Ho that analyzed data on more than 14,000 patients from 984 healthcare facilities. They are set to become the official worldwide staging guidance in the coming year.

“These findings represent compelling evidence for staging modification,” said Robert Figlin, MD, interim director of Cedars-Sinai Cancer and the Steven Spielberg Family Chair in Hematology Oncology. “It is a challenging endeavor, but it improves the information and care that we are able to offer our patients; Cedars-Sinai Cancer is honored to be part of this international effort.”

Ho suggested that patients with newly diagnosed HPV-positive throat cancer ask their care team how these new guidelines have shaped their staging and treatment options.

“Patients should ask their caregivers how these new guidelines impact the clinician’s thinking about the patient’s staging, prognosis and which treatment to offer,” Ho said.

Additional Cedars-Sinai authors include Brian O’Sullivan.

Additional authors include Shao Hui Huang, Michael Luu, Mererid Evans, Robert L. Ferris, James S. Lewis Jr., Raja R. Seethala, Sue S. Yom, Hisham Mehanna, Barton F. Branstetter, Nabil F. Saba, Snehal G. Patel, and William M. Lydiatt.

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In a study published in the peer-reviewed journal Cell Stem Cell, investigators detail how they created “ALS on a chip” and the clues the specialized laboratory chip has already produced about nongenetic causes of the disease, also known as Lou Gehrig’s disease.

The work builds on previous studies where adult cells from ALS patients were reverted into stem cells. The cells were then pushed forward to produce motor neurons, which die in the disease, causing progressive loss of the ability to move, speak, eat and breathe.

In this study, the motor neurons from ALS patients were seeded into the top channels of microengineered chips. Cells that make up the blood-brain barrier were seeded into the bottom channels of the chips. The two channels are connected through a porous membrane that allows investigators to flow fluids through the chips in order to mimic blood flow.

Investigators created a second group of the specialized chips using cells from individuals who did not have ALS, then used advanced technologies to analyze more than 10,000 genes in the motor neurons in both groups of chips.

“In our early work, we couldn’t detect many differences between the motor neurons of patients with ALS and those from healthy individuals,” said Clive Svendsen, PhD, executive director of the Board of Governors Regenerative Medicine Institute at Cedars-Sinai and senior author of the study. “But those studies employed traditional lab culture that is static like a pond. In the body, blood vessels provide constant fluid flow to bring in nutrients and take away waste—and may even provide other types of support to motor neurons.”

In the specialized chips, the motor neurons matured more completely than they would in a static dish, and investigators could detect distinct differences in the cells from patients with ALS.

“We were intrigued to find that signaling for glutamate, a chemical that sends excitatory messages between neurons, was altered in the ALS motor neurons,” Svendsen said. “Excessive release of glutamate has long been considered a possible cause of ALS, and one of the few drugs approved to treat the disease targets this neurotransmitter. The changes we found don’t seem to cause any issues for the motor neurons when they are young, but over many years it is possible that this increased glutamate signaling may be part of why motor neurons die in ALS.”

Svendsen said that while these results are exciting, the team’s next task is to determine whether this increased glutamate signaling directly leads to the dysfunction or death of the cells. He also noted that glutamate is likely only one piece in a much larger puzzle that underlies the cause of ALS.

“These models allow us to better understand the very earliest stages of the disease process,” Svendsen said. “We haven’t connected all the dots yet, but based on these findings we have a model that will allow us to test our theories. If we can show that glutamate signaling eventually makes the ALS motor neurons sick, for instance, we can apply drugs to the blood vessel side of the chip to mimic a clinical trial. Those experiments are underway.”

Additional authors include Deepti Lall, Michael Workman, Samuel Sances, Briana N. Ondatje, Shaughn Bell, George Lawless, Amanda Woodbury, Dylan West, Amanda Meyer, Andrea Matlock, Vineet Vaibhav, and Jennifer E. Van Eyk.

Funding: This work was supported by NIH-NCATS grants 1UG3NS105703-01 and 1UG3TR003264-01, and funding from The ALS Association.

Cedars-Sinai owns a minority stock interest in Emulate, the company that produces the study’s microfluidic Organ-Chips. An officer of Cedars-Sinai also serves on Emulate’s Board of Directors. C.N.S serves on the advisory board of Cell Stem Cell.

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The Y chromosome is one of two chromosomes that determine biological sex in mammals. Females have two X chromosomes, males have one X and one Y chromosome, and it is common for males to lose the Y chromosome in some of their cells as they age.

Cedars-Sinai research published in 2023 found that loss of the Y chromosome in bladder cancer cells in men helped those cells evade the body’s immune system, allowing the cancer to grow. However, tumors with loss of the Y chromosome also were more susceptible than those with an intact Y chromosome to immune checkpoint therapy.

Given the previous findings, that Y chromosome loss in cancer cells was problematic in most male tumors, study co-senior authors Simon Knott, PhD, assistant professor of Biomedical Sciences at Cedars-Sinai, and Dan Theodorescu, MD, PhD, wanted to investigate the consequences of Y chromosome loss in males with other types of cancer, Knott said. 

Using large publicly available datasets, the new study examined loss of the Y chromosome in cancer cells from a range of cancers. Unexpectedly, the investigators found that many other cell types associated with tumors also had Y chromosome loss, prompting further investigations, Knott said.

“When we started to investigate Y loss in other cells in the tumor, our jaws dropped because the link between loss of the Y chromosome in cancer cells and in immune cells from the same tumor was so striking,” Knott said. “Our work showed that if cancer cells lost the Y chromosome, it was very likely immune cells would also have lost the Y chromosome. Losing the Y chromosome in both these cell types at once correlated with hyperaggressive cancer cells and malfunctioning immune cells that are meant to attack the cancer cells. This creates an aggressive tumor with very poor outcomes.”

In addition to the cancer databases, investigators confirmed their findings by looking at loss of Y in patient tumor samples and in preclinical studies using additional techniques to measure Y chromosome loss, which confirmed their findings.

The findings could also have implications for patients receiving T-cell therapies, where immune cells called T-cells are harvested from a patient, altered in the lab so that they are more effective in fighting cancer, then delivered back to the patient.

“Our findings suggest that screening for loss of the Y chromosome in those T-cells or any product generated from them before being given back to a patient could be extremely important,” Knott said. “We predict that cellular therapies with T-cells lacking the Y chromosome will be significantly less effective than those with an intact Y chromosome.”

Further research is needed to help investigators understand how best to adapt these therapies to account for loss of Y.

“Given that a high percentage of older, healthy men experience loss of the Y chromosome in at least some of their cells, these findings could affect many cancer patients,” said Robert Figlin, MD, interim director of Cedars-Sinai Cancer and professor of Medicine and Biomedical Sciences. “Continued investigation into how to translate these findings to more effective therapies fits well with our focus on precision medicine as a way to improve patient outcomes.”

Additional Cedars-Sinai authors include Xingyu Chen, currently at Johns Hopkins University; Yiling Shen; Suhyeon Choi; Mukta Basu; Lena Hoelzen; Martina Tufano; Hany A. Abdel-Hafiz; Saravana Kumar Kailasam Mani; Maryam Ranjpour; Jiani Zhu; V. Krishnan Ramanujan; Ekaterina K. Koltsova; Vinicius Calsavara; and Dan Theodorescu, currently at the University of Arizona.

Funding: This work was supported in part by NIH grant CA278732.

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