As an essential part of the immune system, T cells are able to recognize and destroy tumorous and virus infected cells. T cell mediated immunity is dictated by signals transduced through many different receptors on its surface that binds to their respective ligands from the target cell. One type of signal is generated by the T cell antigen receptor (TCR) which recognizes peptide antigens (Signal 1). The second type of signal comes from a number of coreceptors that regulate the T cell mediated immune response either positively or negatively (Signal 2). Cancer and viruses are able to hijack some coreceptors to escape immune attack. Perturbation of the coreceptor-ligand interactions using antibodies have proven durable clinical benefit in a variety of cancer indications. Despite the huge clinical success of extracellular antibodies in cancer immunotherapy, the fundamental intracellular mechanisms of coreceptor signaling remain poorly understood. We have developed a membrane reconstitution system to investigate the precise mechanism of T cell signaling. This reconstitution system, combined with live cell imaging and cell culture assays, has allowed us to identify a costimulatory receptor, rather than the TCR, as the major target for the immune checkpoint receptor programmed-cell-death-protein-1 (PD-1), which is a viable cancer immunotherapy target. Currently, the Hui lab at UCSD is in the process of understanding the mechanisms of coreceptor pathways in T cells. Knowledge from our research will guide rational design of immunotherapy.
Enfu Hui obtained his Ph.D. in 2009 from UW Madison and was a recipient of the American Heart Association Fellowship. He then completed his postdoctoral training at UC San Francisco, supported by postdoctoral fellowships from the Leukemia & Lymphoma Society and Genentech Inc. He joined the Division of Biological Sciences at UC San Diego in July 2016.