The immune system is determined by both positive costimulation and negative coinhibition, generated mainly by the interaction between the B7 ligand family and their receptor CD28 family. We discovered new members of the T cell costimulatory/coinhibitory B7 family and CD28 family including B7x, HHLA2 and TMIGD2, identified KIR3DL3 (an orphan member of the KIR family) as a receptor for HHLA2, and contributed to other immune checkpoints such as B7-H3, Tim-3, ICOS, KIR2DL5/PVR, PD-L1/PD-1, BTNL2, etc. We are using a variety of experimental approaches (gene knock-out/transgenic mice, humanized mice, monoclonal antibodies, single-cell RNA sequencing, crystal structure, patients samples, imaging, etc) to understand how new immune checkpoints regulate T cell and other immune cell activation and tolerance. Current emphasis in the lab is placed in the following areas: New immune checkpints and cancer immunotherapies, autoimmune diseases and immunotherapies, metabolic diseases and immunotherapies.
Our research has formed scientific foundation and core intellectual property for several start-up drug companies. A new immune checkpoint inhibitor from our lab has successfully finished phase I clinical trials to treat cancer patients who have failed standard treatments or lack effective treatments, and is currently in combination therapy clinical trials combined with anti-PD-1 in patients of advanced solid tumors or combined with demethylation drugs in patients of recurrent/refractory Acute Myeloid Leukemia, Myelodysplastic Syndromes, or lymphoma. Another novel first-in-class immune checkpoint inhibitor from our lab is expected to start clinical trials in 2023.
Since 2008 the lab has mentored total 48 trainees of MD-PhD or PhD students, postdoctoral fellows, clinical fellows, and visiting scientists. Most of trainees have subsequently moved on to independent careers in academic universities, medical centers, biopharmaceutical industry, and US government agencies.
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