Hannah Bell, MD, PhD, Postdoctoral Fellow University of Michigan Area of Research: All Cancers Perforin, a crucial T cell protein, mediates tumor cell death by a poorly understood mechanism. Dr. Bell’s preliminary data suggests that perforin induces ferroptosis in tumor cells by increasing intracellular iron. Ferroptosis is a programmed cell death pathway dependent on iron. The long-term goal is to develop translational therapies to enhance perforin-induced ferroptosis. Her central hypothesis is that perforin increases intracellular iron, triggering ferroptosis and inhibiting metastasis and immunotherapy resistance. This hypothesis will be tested through two specific aims: 1) Define the molecular mechanisms of perforin-mediated ferroptosis; and 2) Characterize the contribution of perforin-induced ferroptosis to anti-tumor immunity. In aim 1, Dr. Bell will use genetic, pharmacologic, and dietary approaches to mechanistically define perforin-induced ferroptosis. In aim 2, she will study the role of perforin-induced ferroptosis in metastatic, primary, and immunotherapy in vivo models. Aim 2 will also bioinformatically explore how perforin expression contributes to patient immunotherapy response. Dr. Bell’s proposed research will elucidate the ferroptosis-inducing function of perforin and its contribution to anti-tumor immunity. This innovative research explores a previously unknown mechanism of perforin killing molecularly and translationally. Projects and Grants Beyond lysis: deciphering the role of perforin-mediated ferroptosis in anti-tumor immunity University of Michigan | All Cancers | 2025 | Weiping Zou, MD, PhD
