Byersdorfer Lab

Dr. Byersdorfer is a physician-scientist whose research interests focus on understanding the biology of GVHD-causing T cells following allogeneic transplantation. The goal of these efforts is to develop novel therapeutics to mitigate graft-versus-host disease (GVHD) while preserving homeostatic immune reconstitution and graft-versus-leukemia effects. Specifically, Dr. Byersdorfer’s research program seeks to elucidate the specific metabolic pathways that are upregulated in GVHD-causing T cells. His efforts represent a novel approach to understand disease pathogenesis and will likely lead to new and innovative therapies. In addition, his findings on T cell metabolism will almost certainly have implications beyond the field of blood and marrow transplantation to impact solid organ transplantation and improve our ability to mediate long-term anti-leukemia responses.

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. Dr. 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 exact mechanism 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. In recent research, they have found that transcriptional control of fat oxidation depends upon signaling through peroxisome proliferator-activated receptors (PPARs), notably PPAR-δ.  His lab is currently generating PPAR-δ deficient mice to determine its role in GHVD propagation and more importantly, to define whether PPAR-δ represents a potential therapeutic target for treatment of GVHD in humans. 

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 will attempt to improve the in vivo persistence of CAR T cells by reprogramming their metabolism through constitutive expression of activated AMPK or PPAR-δ. These changes are expected to increase in vivo T cell and thus increase anti-leukemia efficacy.

Current Members

Craig Byersdorfer, MD, PhD - Principal Investigator

Andrea Dobbs - Research Technician

Erica Braverman MD - Post-Doctoral Fellow

Rebecca Brown - PSTP student

Elisabeth Denby - Technician

Zeyang Yue - Tsinghua Medical Student

 

Educational Opportunities

Byersdorfer Lab welcomes graduate students for rotations in the lab, clinical fellows interested in immune cell metabolism, and medical students as part of the Dean’s Summer Research Program.

Publications

  1. Dolezal JM, Wang H, Kulkarni S, Jackson L, Lu J, Ranganathan S, Goetzman ES, Bharathi S, Beezhold K, Byersdorfer CA, Prochownik EV. Sequential Adaptive Changes in a c-Myc-Driven Model of Hepatocellular Carcinoma. J Biol Chem. 2017. Epub ahead of print. PMID: 28432125
  1. Tkachev V, Goodell S, Opipari AW, Franchi L, Hao, LY, Glick GD, Ferrara JLM, and Byersdorfer CA, Programmed death-1 controls T cell survival by regulating oxidative metabolism. J Immunol. 2015. 194(12):5789. PMID: 25972478
  1. Gleimer, M., Li, Y., Chang, L., Paczesny, S., Hanauer, D.A., Frame, D.G., Byersdorfer CA, Reddy, P.R., Braun, T.M., and S.W. Choi.  Baseline body mass index among children and adults undergoing allogeneic hematopoietic cell transplantation: clinical characteristics and outcomes. BMT. 2015. 50(3):402. PMID: 25531283
  1. G.D. Glick, R. Rossignol, C. A. Lyssiotis, D. Wahl, C. Lesch, B. Sanchez, X. Liu, L.Y. Hao, C. Taylor, A. Hurd, J. LM. Ferrara, V. Tkachev, Byersdorfer CA, L. Boros and A. W. Opipari.  Anaplerotic metabolism of alloreactive T cells provides a metabolic approach to treat graft-versus-host disease. J. Pharm. Exp. Ther. 2014. 351(2):298. PMID: 25125579
  1. Byersdorfer CA, Tkachev V, Opipari AW, Goodell S, Swanson J, Sandquist S, Glick GD, and JLM Ferrara. Effector T cells require fatty acid metabolism during murine graft-versus-host disease. Blood. 2013. 122(18):3230-3237. PMID: 24046012