Craig Byersdorfer, M.D., Ph.D.

  • Assistant Professor of Pediatrics and Immunology

Major Lectureships and Seminars

  • “An unexpected role for AMP‐activated protein kinase (AMPK) during graft‐versus‐host disease”, Hem/Onc/BMT seminar series, Ben Towne Cancer Center, Seattle, WA, May 2016
  • “How I Learned to Stop Worrying and Love the Bomb Biochem.” Keynote address, Annual Physician Scientist Training Program research symposium, University of Pittsburgh. Nov 2016

Professional Affiliations/Society Memberships

  • American Society of Hematology
  • American Society for Blood and Marrow Transplantation
  • American Association of Immunologists
  •  2nd Appointment, Department of Immunology, University of Pittsburgh

Education & Training

  • MD: Washington University School of Medicine St Louis, MO
  • Residency: University of Michigan Medical School Ann Arbor, MI
  • Fellowship: University of Michigan Medical School Ann Arbor, MI

Research Interests

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.

Clinical Research

Reprogramming human T cells. Having determined the metabolic pathways present in murine alloreactive T cells, the Byersdorfer lab moved on to discover whether similar metabolic changes occur in human T cells during GVHD and whether their elimination mitigates GVHD. Clinical samples will be collected from human patients at the diagnosis of acute GVHD and evaluated to determine the metabolic pathways present. The lab continued pursuing studies using gene-editing programs like CRISPR-Cas9 to eliminate metabolic proteins in human T cells and then test them in xenogeneic models of GVHD before transitioning them to clinical application.