Liver-Related Work

1. Epigenetic Regulation of Human Memory CD8 T Cells in Solid Organ Transplantation: One of the cardinal features of long-lived immunity is the development of cytotoxic memory CD8 T cells that can still remember our past history of infections. They are endowed by two fundamental characters: (1) maintenance of their effector function at steady state and (2) a rapid recall response upon pathogen re-exposure. However, they can behave similarly to the main theme of duality found in the famous book “Strange Case of Dr. Jekyll and Mr. Hyde”. For instance, memory CD8 T cells that protect the host from pathogen re-exposure can start attacking a transplanted donor organ in the setup of solid organ transplantation. In this case, they “see” the donor’s organ as foreign and attack it, resulting in organ rejection. Consequently, the ultimate goal of solid organ transplantation is to induce donor-specific graft tolerance without compromising host protection against pathogens. However, it is clear that allo-reactive memory CD8 T cells are one major barrier against induction of graft tolerance. Hence, there is a critical need to understand the molecular mechanism(s) regulating the development and maintenance of human allo-reactive memory CD8 T cells. Since transcriptional regulation is mediated in part by epigenetic mechanisms, we approached the above-mentioned goal through the lens of epigenetics with a focus on DNA methylation. 
2. Epigenetic Regulation of Human Memory CD8 T Cells During Immune Aging:  The number of Americans aged 65 and older is projected to grow from 49.2 million in 2016 to over 94 million by 2060. Despite the increase in life expectancy, as we age our immune system reaches a state of immune senescence, resulting in susceptibility to a wide range of infections and impaired immune response to vaccines. Hence, it is crucial to define the molecular mechanisms regulating acquisition and maintenance of such impairment, which will ultimately allow us to develop strategies for rejuvenating the effector function of cytotoxic memory T cells (CD8 T cells) in the elderly population.

Research Assistant Professor
Department of Surgery, Starzl Transplant Institute