Grace Bigelow-Leth L&S Biological Sciences
Targeted Protein Degradation to Induce Ferroptosis in Cancer
All organisms rely on built-in systems that eliminate damaged or harmful cells to maintain healthy tissues. In cancer, however, these protective pathways can be bypassed, allowing malignant cells to continue growing. This makes regulated cell death pathways attractive targets in oncology. One promising pathway is ferroptosis, a form of cell death driven by iron-dependent damage to lipids in cellular membranes. Ferroptosis suppressor protein 1 (FSP1) helps cancer cells avoid ferroptosis by protecting membranes from this damage. Recent studies suggest that some tumors become highly dependent on FSP1 for survival, and loss of FSP1 can dramatically slow tumor growth.
My project explores a new way to target FSP1 using proteolysis targeting chimera (PROTAC) molecules, which direct proteins to the cell’s own recycling machinery for destruction. Building on an existing FSP1 inhibitor developed in the Olzmann Lab, I will test whether PROTAC molecules can bind FSP1 and effectively remove it from cells. This work could help clarify whether targeted FSP1 degradation can complement ongoing efforts to develop ferroptosis-based cancer therapies.
Message To Sponsor
Thank you so much for your support in funding my summer research! I am deeply grateful not only for the opportunity to contribute to research that may help advance future cancer therapies, but also for the chance to experience what a full-time research position looks like. This summer has made it clear that graduate school is the right path for me, and this project has been a pivotal stepping stone as I move toward that goal. Thank you for investing in the next generation of researchers—I'm honored to be one of them.