The research program in the Bradley Lab is focused on understanding the regulation of T lymphocytes in virus infections where the immune response
results in viral clearance and the development of immunologic memory, and in chronic virus infections where the ongoing immune response leads to viral
persistence and immune dysregulation.
We are guided by these studies to interrogate cellular mechanisms that can be modulated to promote better responses not only to virus infections, but also
to relieve immune inhibition in the setting of cancer where T cells progressively lose function. Understanding adhesion mechanisms underlie the ability of
T cells to become localized in tissues to eradicate infections and tumors is a key underpinning of our work.
Our current focus is on two molecules that can function on T cells to initiate the processes that lead to their migration from the blood into tissue, CD44 and
PSGL-1 (P-selectin glycoprotein-1). We have found that both of these receptors have key regulatory functions that are independent of their roles in migration.
These proteins regulate the magnitude of T cell responses, as well as the survival and memory formation by T cells by different mechanisms, affecting processes in the
T cell and stromal cell compartments.
Our ongoing studies of these immune checkpoint regulators using in vivo models indicate that they are promising therapeutic targets to enhance T cell responses to infections
and cancer as well as to inhibit T cell responses in autoimmunity. We are therefore pursuing translational studies with the UCSD Moores Cancer center to analyze their regulation
in human T cells in an effort to enhance patient responses to their tumors using in vivo modeling. In addition working to develop biologics for treatment of patients with autoimmunity