New Grant to Study Graft-Versus-Host Disease

Craig A. Byersdorfer, MD, PhD, is a pediatric hematologist/oncologist in the Division of Blood and Marrow Transplantation and Cellular Therapies, with a research focus on understanding posttransplant complications, specifically graft-versus-host disease (GVHD) and the role that T cells play in driving this condition.

“Graft-versus-host disease affects 30 to 50 percent of transplant patients and has been an intractable problem for decades. We even know that GVHD is a T-cell driven phenomenon. If we can modulate T-cell metabolism in a way that shuts down the most active cells driving the condition, or identify metabolic ways to eliminate them altogether, we will make blood and marrow transplantation (BMT) a safer and more effective therapy for individuals with otherwise incurable diseases,” says Dr. Byersdorfer.

In February, Dr. Byersdorfer received one of four Amy Strelzer Manasevit Research Program grants awarded by the Be The Match Foundation® in 2018. Handed out for either clinical or preclinical investigation of complications arising after allogeneic hematopoietic stem cell transplantation (alloHSCT), the award is administered over three years with a maximum support of $240,000.

A central focus of Dr. Byersdorfer’s research is how T cell metabolism and the targeting of metabolic pathways, may be used to help limit, or even eliminate, GVHD post-transplant. Previous research by Dr. Byersdorfer and his team has demonstrated that the cellular energy sensor, AMP-activated protein kinase (AMPK), plays a necessary role in T cells in GVHD models, and his belief is that modulating this pathway may result in a decreased incidence of GVHD following allogeneic transplantation in humans.

Dr. Byersdorfer’s new award will be used to investigate the mechanism of AMPK’s action in post-transplant T cells and determine the relationship by which AMPK is linked to pro-inflammatory cytokines like IL-6. “We seek to further clarify the relationship between AMPK, metabolic stress, and cytokine sensitivity, and to translate these findings into human T cells. If successful, these new studies will help to define novel mechanisms downstream of metabolic reprogramming in activated T cells, that may facilitate development of innovative treatments for GVHD, while at the same time maintaining homeostatic immunity and anti-leukemia responses following alloHSCT,” says Dr. Byersdorfer.