Georgetown Lombardi Visiting Professor and Grand Rounds Lecture Series Featuring Yi Zhang, MD, PhD
“Alloimmunity, Anti-Tumor Effects, Dendritic Cells and Epigenetic Regulation”
Yi Zhang, MD, PhD
Hackensack Center for Discovery and Innovation
Sponsor: Dr. David Perlin
Dr. Yi Zhang is a director, member scientist at Center for Discovery and Innovation (CDI), Hackensack Meridian School of Medicine. Dr. Zhang was awarded his MD and PhD degree from The University of Tokyo (Japan, 1998) and completed his postdoctoral training at The University of Pennsylvania (2003). Dr. Zhang was a professor with tenure at Temple University and very recently joined CDI from September 1, 2021.
Dr. Zhang has long-term interest in understanding of pathophysiology of graft-versus-host disease (GVHD) in the setting of allogeneic hematopoietic stem cell transplantation (allo-HSCT), and epigenetic regulation of alloimmunity and tumor immunity. Specifically, Dr. Zhang has discovered the importance of dendritic cells (DCs) and DC expressing the Notch ligand delta-like ligand 4 (Dll4) in the regulation of alloreactive T cell responses and GVHD. Dr. Zhang also introduced the concept of alloantigen-sensitized stem cell memory T cells (TSCM) in sustaining alloreactive T cell responses and GVHD (Nat Med 2005). This concept of TSCM stimulates many other groups to develop novel strategies for improving the efficacy of cancer immunotherapy, including CAR-T cell therapy. Building on these studies, Dr. Zhang has developed a research program to investigate the epigenetic mechanisms that control the generation, maintenance and function of antigen-driven T cells. For example, Dr. Zhang identified that inhibition of T cell Ezh2, which catalyzes histone H3 lysine 27 trimethylation, reduces GVHD in mice undergoing allo-HSCT. His studies also illuminate the crucial role of Ezh2 in regulating memory T cells and their anti-tumor immunity. Dr. Zhang’s laboratory has made a continuous stream of novel fundamental contributions in GVHD and T cell tumor immunity. Currently, Zhang and his colleagues are developing novel and clinically relevant approaches to modulate alloimmunity and to improve the efficacy of cancer immunotherapy, including: 1) establishment a cellular therapy strategy to program donor T cells that preserve potent anti-leukemia activity without causing severe GVHD using both DLL4+ DCs and plasmacytoid DCs; 2) development of a new approach of destabilizing T cell Ezh2 protein using pharmacological inhibitors to modulate alloimmunity; and 3) discovery of novel epigenetic drugs (e.g., targeting CDK9, CDK7, DOT1L and DNMTs, etc.) that can reduce tumor resistance to CAR-T cell therapy to improve the efficacy of immunotherapy for solid tumor.
Lecture Series Presented by Georgetown Lombardi Comprehensive Cancer Center