BIOE Big Ten Seminar: Mohammad Fallahi Sichani
Friday, November 30, 2018
9:00 a.m.-10:00 a.m.
A. James Clark Hall, Room 2132
Dr. Giuliano Scarcelli
Dr. Mohammad Fallahi Sichani
University of Michigan
Maximizing Oncogene Addiction in Tumor Cells By Epigenetic Modulation: Pushing the Limits of Molecularly Targeted Therapies
Tumor cells carrying driver oncogenes such as mutated BRAF, EGFR and EML4-ALK appear to sustain an oncogene addiction state, in which growth and survival are highly dependent on the continued activity of the oncogenic pathway. The discovery of such dependencies has informed drug development strategies for a variety of cancers. However, patient responses to therapeutic inhibitors of oncogene action are often incomplete and limited by drug resistance. Although genetic factors in resistance are part of the story, emerging evidence suggests that tissue-specific epigenetic mechanisms and reprograming following oncogene inhibition can induce adapted states where there is reduced dependence on the oncogenic activity. These epigenetic states generate heterogeneous sub-populations of drug-tolerant cells that not only limit drug effectiveness, but also constitute a reservoir from which genetically resistant clones are ultimately selected and contribute to disease progression. This represents a major challenge facing the development and use of targeted therapies for a variety of cancers. Our research aims at addressing this problem. We are using an integrated strategy, combining long-term live-cell microscopy, high-throughput measurement, multiplexed single-cell analysis and computational modeling, to dissect the poorly understood epigenetic states at the single-cell level, identify their key regulators, and predict and test efficient ways, via epigenetic modulation, to block the heterogeneous populations of drug-resistant cells and maximize tumor cell killing. Our findings will help us utilize targeted therapeutics more generally, more precisely, and more effectively to cure cancer.
About the Speaker
Mohammad Fallahi-Sichani obtained his B.Sc. degree in Biotechnology from the University of Tehran in 2007. In 2012, he earned a Ph.D. in Chemical Engineering from the University of Michigan, where he was awarded a Rackham Predoctoral Fellowship and a Richard and Eleanor Towner Prize for Outstanding PhD Research. His PhD work co-mentored by Jennifer Linderman and Denise Kirschner combined multi-scale modeling approaches with wet-lab experiments for the study of mechanisms by which TNF signaling determines immunity to M. tuberculosis infection. He then joined the laboratory of Peter Sorger at Harvard Medical School as a Life Sciences Research Foundation (LSRF) postdoctoral fellow and was later awarded a K99/R00 Pathway to Independence Award from the NIH/NCI. His postdoctoral research focused on the development of systems biology approaches to reveal the mechanisms of adaptive resistance and fractional response of cancer cells to anti-cancer drugs. In 2017, Mohammad joined the University of Michigan Department of Biomedical Engineering as an Assistant Professor. Since then, he has been the recipient of the V Foundation for Cancer Research V Scholar Award (2017) and the DoD CDMRP Career Development Award (2018). Research in the Fallahi-Sichani lab is at the interface of bioengineering, cancer biology and quantitative pharmacology, and aims at designing, building and utilizing new experimental and computational tools to analyze multi-scale processes that control oncogenesis and therapeutic response in human tumors.