Duke Sub–PI
Jen-Tsan (Ashley) Chi, MD, PhD
Co-Leader, Cancer Biology Program at Duke Cancer Institute; Associate Professor of Department of Molecular Genetics and Microbiology, Duke University
Research Interests
The genetic determinants and disease relevance of ferroptosis – ferroptosis is a newly recognized form of cell death that is characterized by iron dependency and lipid peroxidation. The importance of ferroptosis is being recognized in many human diseases, including cancers, ischemia injuries and neurodegeneration. Previously, we have identified the profound cystine addiction of renal cell carcinoma, breast cancer cells and ovarian cancer cells. Based on the concept that cystine deprivation triggers the ferroptosis due to the unopposed oxidative stresses, we have performed functional genomic screens to identify many novel genetic determinants of ferroptosis. For example, we have found that DNA damage response and ATM kinase regulate ferroptosis via affecting iron metabolism. This finding supports the potential of ionizing radiation to trigger DNA damage response and synergize with ferroptosis to treat human cancers. In addition, we found that ferroptosis is highly regulated by cell density. When cells are grown at low density, they are highly susceptible to ferroptosis. In contrast, the same cells become resistant to ferroptosis when grown at high density and confluency. we have found the Hippo pathway effectors TAZ and YAP are responsible for the cell density-dependent ferroptosis. Right now, we are pursuing several other novel determinants of ferroptosis that will reveal surprising insights into this new form of cell death.
Research Plan
We are employing brain slice model to investigate the potential of ferroptosis modulators to affect the neurodegenerative diseases and brain tumors.
