In the Byersdorfer lab, we study immune cell metabolism during the dynamic interplay of immune reconstitution and T cell activation following allogeneic stem cell transplantation (alloSCT). The goal of the lab is to define metabolic pathways up-regulated in lymphocytes following alloSCT, particularly in the T cells which cause graft-versus-host disease (GVHD). We use animal models and genetically modified donor cells to test fundamental questions regarding post-transplant T cell metabolism. Our current work falls into three categories:
Effector T cell metabolism during GVHD. Effector T cells undergo significant metabolic change as they transition from quiescent cells to activated effectors during GVHD initiation. Our data suggest that alloreactive T cells increase their reliance on multiple forms of metabolism, including an increased reliance on the oxidation of fat. We use genetic models and metabolic inhibitors to explore the metabolic and molecular changes that make this adaptation to oxidative metabolism possible, with the future hope of intervening against pathogenic T cells while still preserving homeostatic and physiologic immune responses post-transplant.
Augmentation of graft-versus-leukemia effects. Hematologic malignancy is a common indication for blood and marrow transplantation and we are using our growing knowledge of T cell metabolism to uncover novel ways to metabolically enhance T cell responses against leukemia cells in the post-transplant environment. We continue to use genetic and pharmacologic manipulation of T cells, as well as retrovirally-induced models of human leukemias, to ask probing questions regarding T cell-driven, anti-leukemia biology.
Translation to human T cells. Our long-term goal in the lab is to facilitate metabolic discoveries that will translate into better treatments for patients undergoing allogeneic transplantation. To this end, we are actively elucidating metabolic pathways present in human T cells in both clinical samples from patients with acute GVHD and in samples from xenogeneic GVHD models. The goal is to leverage this new knowledge into rationally-designed clinical trials for GVHD prophylaxis and treatment.
The Byersdorfer group welcomes graduate students for rotations in the lab, as well as clinical fellows interested in immune cell metabolism and medical students as part of the Dean’s Summer Research Program.