Craig A. Byersdorfer, MD, PhD

Craig Byersdorfer focused on the biology of GVHD-causing T cells following allogeneic transplantation to develop novel therapeutics to mitigate graft-versus-host disease (GVHD) while preserving homeostatic immune reconstitution and graft-versus-leukemia effects. Specifically, Byersdorfer’s research program sought to elucidate the specific metabolic pathways that are upregulated in GVHD-causing T cells. His novel approach to disease pathogenesis continued to aim at innovative therapies. His findings on T-cell metabolism have implications extending beyond BMT to solid organ transplantation and long-term anti-leukemia responses.

Laboratory-Based Research

The role of AMP-activated protein kinase in alloreactive T cells. AMPK is a well-known energy sensor and is activated early in T cells during a GVHD response. Byersdorfer has shown that lack of AMPK leads to decreased rates of GVHD but preserves anti-leukemia responses. Further work has demonstrated that a lack of AMPK has consequences for both effector T cells and the generation of regulatory T cells, favoring a tolerogenic response. Future studies will utilize animal models and AMPK KO cells to determine the mechanisms of improved GVHD in the absence of AMPK signaling.

Transcriptional control of fatty acid metabolism in alloreactive T cells. The Byersdorfer lab has previously demonstrated that GVHD-causing T cells increase their dependence on the oxidation of fat. The lab found that transcriptional control of fat oxidation depends on signaling through peroxisome proliferator-activated receptors (PPARs), notably PPAR-δ. His lab continued generating PPAR-δ deficient mice to determine its role in GHVD propagation and to define whether PPAR-δ is a potential therapeutic target for GVHD treatment.

Using metabolic manipulation to improve anti-leukemia responses. One of the challenges to treatment with chimeric antigen receptor (CAR) T cells for acute lymphoblastic leukemia is a frequent inability to persist in vivo. The Byersdorfer lab sought to improve the in vivo persistence of CAR T cells by reprogramming their metabolism through constitutive expression of activated AMPK or PPAR-δ, and thus increase anti-leukemia efficacy.