T lymphocytes play a central role in the initiation and regulation of the adaptive immune response to antigen, whether foreign or native. The outcome of T cell engagement of antigen is determined by both positive and negative signals, costimulation and coinhibition, generated mainly by the interaction between the B7 family and their receptor CD28 family. We use a variety of experimental approaches (gene knock-out mice, transgenic mice, monoclonal antibody, crystal structure, imaging, etc) to understand how new costimulatory and coinhibitory members of the B7/CD28 families regulate T cell function. Upon activation in lymphoid organs, T cells differentiate and migrate to the periphery where they carry out their effector functions. However, little is known about how costimulation and coinhibition control T cell responses in peripheral non-lymphoid organs where most diseases occur. Our long-term goal is to elucidate the mechanisms by which costimulation and coinhibition regulate T cells in peripheral non-lymphoid organs, and to translate the lessons learned in these studies towards developing new therapeutic strategies for immune-related diseases such as cancer, autoimmune disorders, infectious diseases, and transplantation rejection.
We are interested in translational research and seek to move our findings in basic research more quickly and efficiently into medical practice. FDA has approved four new drugs developed from the B7/CD28 families. We believe that research on T cell costimulation and coinhibition holds promise for development of novel therapies and diagnoses.
We have discovered new members of the T cell costimulatory/coinhibitory B7/CD28 families, B7x, HHLA2, TMIGD2. Current emphasis in the lab is placed in the following areas:
Novel drugs development: Translational medicine of T cell costimulation and coinhibition
In vivo functions of new B7/CD28 pathways
Human cancer-associated new B7/CD28 pathways and cancer immunotherapy
Roles of new B7/CD28 pathways in autoimmune diseases and immunotherapy
Relationship between new B7/CD28 pathways and infection.
Functional and structural characterization of new members of the immunoglobulin superfamily