Following viral or bacterial infection, numerous components of the immune response play a role in recognizing, engaging and eradicating the offending pathogen. T cells are particularly central to protection from a wide variety of infections. A key hallmark of protective T cell responses is the long-lived (in many cases life-long) persistence of memory T cells after the pathogen is cleared. Because memory T cells are present at elevated frequencies and recognize the pathogen quickly, they are able to provide rapid protection upon encountering the same pathogen a second time. While many successful vaccines of the past have relied on the development of antibody responses for their protective effect, future disease challenges will require the induction of cell-mediated protection provided by T cells. The research focus of the Williams laboratory is to understand the nature of T cell intrinsic signals, such as the T-cell receptor, and T cell extrinsic signals, such as inflammation, in promoting the ability of T cells to acquire the functions that allow them to eradicate pathogens and form long-lived immunological memory.
Signals that promote long-lived memory T cells
My lab is focused on understanding the signals that occur early in the response to infection that promote the development of long-lived memory T cells. To accomplish this, we employ several models of acute infection in micw, including Listeria monocytogenes, lymphocytic choriomeningitis virus (LCMV), vaccinia virus and influenza virus. By using these models, we hope to pinpoint some of the signals that drive memory T cell differentiation. We are particularly focused on the role of the T cell receptor in driving this process, and current projects in the lab focus on understanding the role of TCR signal strength in shaping the effector functions of the T cell response.
Regulation of T cell activity in the tumor microenvironment
A major obstacle in harnessing the immune system to combat cancer is the ability of many tumors to inhibit T cell function. We are engaged in basic, pre-clinical and translational studies to achieve a better understanding of how T cell activation and function are regulated in the tumor microenvironment, and to identify therapeutic targets to enhance T cell activation that can complement existing checkpoint blockade therapies. The end goal is to improve disease outcomes by inducing long-lived, highly functional anti-tumor memory T cells that promote durable cancer remission.