Investigator Asst Prof (M) Ragon PIs 2, Mass General Research Institute

Assistant Professor Biology Department, Massachusetts Institute of Technology

aging; metabolic networks and pathways; t cells; tumorigenesis We investigate crosstalk between CD8⁺ T cells and their environment at a molecular level, by dissecting the biological and metabolic programs engaged under conditions of stress. Using an array of approaches to model and perturb the local microenvironment, our research aims to reveal both the adaptive molecular changes as well as intrinsic vulnerabilities in T cells that arise within the tumor niche. Our goal is to understand how disease states remodel the fundamental mechanisms that regulate immune cell function and contribute to pathogenesis.

Why do rapidly dividing T cells need lipids?

Fatty acids and other lipids are chronically dysregulated across many human disease states, including obesity, aging, and cancer. Lipids belong to a chemically diverse class of metabolites, yet little is known about the molecular fates of lipids in rapidly dividing cells, particularly with complex lipid mixtures that are encountered under normal physiology. The Ringel lab seeks to reveal the metabolic, structural, and signaling fates of lipids in T cells that regulate immune responses.

How does the aging immune system interact with tumors?

While aging is a universal cancer risk factor, little is known about how the aging immune system interacts with a growing tumor. The T cell pool is remarkably susceptible to age-related changes that reduce immune function. T cells are also responsible for tumor surveillance, where a healthy T cell compartment can eliminate malignant cells before they grow into tumors. Our goal is to identify molecular axes of T cell dysfunction during aging that contribute to tumorigenesis and can be targeted to improve cancer prevention and therapy.

How do metabolic networks regulate tumorigenesis?

Metabolic reprogramming is hallmark feature of both tumor and immune cells, which coexist in the tumor niche and share finite resources. There is considerable overlap between the nutrient preferences in tumor cells and the metabolic dependencies of T cells. Yet surprisingly little is known about the impact of cancer metabolism on T cells within the same tumor niche beyond competition for major carbon sources. Using a variety of experimental approaches and model systems, we aim to identify and investigate networked relationships that govern tumor progression and response to therapy.