Featured Postdoc Research

Molecular Mechanisms of Breast Cancer and Therapies for Triple-Negative Breast Cancer

Lead: Stacey Chung, Postdoctoral Scientist

Project Summary

Breast cancer is a heterogenous disease in which the basal-like breast cancer subtype, commonly referred to as triple-negative breast cancer (TNBC), is the most aggressive as patients present with high histologic grade, metastasis to the lung and brain, and poor prognosis. TNBC is marked by the absence of estrogen receptor, progesterone receptor and human epidermal growth factor receptor-2 expression. The only form of systemic treatment is chemotherapy for this subtype. Therefore, targeted therapy is urgently needed for TNBC. 

Current treatments being tested for breast cancer include targeting DNA repair pathways to initiate DNA damage-induced cell death. Topoisomerase 1 (TOP1) inhibitors have been tested as potential drug therapies for breast cancer and some have been FDA-approved for cervical and colorectal cancer, including topotecan and irinotecan. Targeting TOP1 is important since it functions to relax supercoiled DNA to initiate replication and transcription but TOP1 inhibition renders the enzyme unfunctional leading to stalled replication forks and accumulated DNA damage. 

Expected Outcomes

Understanding the molecular mechanism of TOP1 inhibition in TNBC would help us understand which TNBC patients would benefit from this treatment modality. 

Our initial tests treating TNBC cells with topotecan show astonishing results in which cells are either highly sensitive or resistant to treatment. We have identified differences in DNA damage response and JNK signaling pathways, but want to further characterize biomarkers that can be used to determine patient response.

Key Collaborators

Microbiome, Gut Microbiota, Nutrition, Diet, Inflammatory Bowel Disease

Lead: Anthony Martin, Postdoctoral Scientist

Project Summary

We study human health and disease through the trillions of bacteria that live in our gut. One of the major determinants of our "microbial identity" is the food we eat. The emergent patterns of microbial growth and productivity reveal both novel and long-evolved relationships between host and microbe that can be leveraged for health. Our goal is to define mechanistic underpinnings to diet's extraordinary impact on the gut microbiome and translate these findings into prospective human studies. We design custom diets and feeding protocols addressing microbiome-based questions across the spectrum of dietary pathologies such as overconsumption in chronic inflammatory and metabolic disease to starvation and malnutrition, as well as lifestyle choices including vegan vs. omnivore preferences.

Currently, we are investigating the role gut microbiota play in nutrient sensing and their ability to mitigate amino acid (AA) deficiency induced by the chronic consumption of protein restricted (PR) diets. We have demonstrated that fiber supplementation to PR diets has a differential impact on attenuating the host metabolic FGF21-stress response to AA deficiency through fiber-induced alterations in gut microbiota. Our findings provide evidence for the utility of specific, microbiome-targeted approaches to harness the metabolic capacity of enteric microbes to improve host nutrition. This presents an attractive method to reconciling diet-induced protein deficiency through interventions formulated to promote growth of microbes capable of influencing host protein status.

Key Collaborators

Donald Layman
Professor Emeritus, Dept. of Food Science and Human Nutrition, University of Illinois, Urbana, IL

Have Questions or Need Help?

Contact us if you have questions or would like to learn more about Cedars-Sinai's Postdoctoral Scientist Training Program.

Alysia Caldwell
Program Coordinator