The Arkansas Integrative Metabolic Research Center will host Jeffrey Rathmell, a professor of pathology, microbiology and immunology from Vanderbilt University at 12:55 p.m. on Wednesday, Jan. 22, in ARKV 0002 (310 Arkansas Ave.).

Rathmell studies T-cell biology with a focus on how metabolic pathways and tissue microenvironments influence the function and fate of lymphocytes in inflammatory diseases and anti-tumor immunity. During this talk, Rathmell will discuss his work on understanding the role of the microenvironment in modulating the function of immune cells and how this can create interesting paradoxes, such as the increased cancer risk due to obesity-induced inflammation as well as increased efficacy of cancer immunotherapy in obese individuals. He will discuss how the metabolic interaction of immune cells with their environment can both drive disease and offer new therapeutic opportunities.

Abstract: T cells in inflamed tissues accumulate stress and mitochondrial damage that remain poorly understood. We have shown that CD4 T cell subsets are metabolically distinct and that each requires a specific metabolic program for their function. We also know that immune cells are subject to microenvironmental factors that shape their metabolism and function, and that systemically, obesity leads to chronic inflammation and is a risk factor for cancer. However, cancer immunotherapy efficacy can be enhanced in obesity; induction of the immune checkpoint molecule PD-1 on tumor-associated macrophages contributes to this paradox and immunotherapy responses in obese individuals. At a microenvironmental level, tissue temperature changes with body location, fever and inflammation, and T cells broadly become more pro-inflammatory under fever temperatures, but a subset of CD4 T cells, Th1 cells, selectively experience mitochondrial stress that activates a heat-sensitive molecular stress circuit. The metabolic interaction of immune cells with their environment can both drive disease and offer new therapeutic opportunities.

Biography: Rathmell studies T-cell biology with a focus on metabolic mechanisms that regulate lymphocyte fate and function. He has developed an interdisciplinary basic and translational research program using genetic and biochemical approaches to discover immunometabolic and microenvironmental mechanisms that drive cancer and autoimmunity. After his undergraduate studies at the University of Northern Iowa, he received his Ph.D. in immunology at Stanford University. He then performed postdoctoral studies at the University of Chicago and the University of Pennsylvania before joining the faculty at Duke University and subsequently Vanderbilt University Medical Center as the Cornelius Vanderbilt Professor of Immunobiology. During this time, he showed that lymphocyte metabolism is dynamically regulated and was the first to show that each T cell subset adopts a specific metabolic program. He is the founding director of the Vanderbilt Center for Immunobiology and co-leader for the Vanderbilt-Ingram Cancer Center Program in Host-Tumor Interactions.

This event is supported by NIGMS of the National Institutes of Health under award number P20GM139768. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

Pizza and beverages will be served. Please contact Kimberley Fuller, fullerk@uark.edu, for more information.

For those unable to attend in person, this seminar will also be available via Zoom.