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, demonstrated the biology and therapeutic potential of the KIR2DL5/PVR pathway, and contributed to other immune checkpoints such as B7-H3, Tim-3, ICOS, 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 cells and other immune cells. 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 is currently in phase II clinical trials in patients with advanced solid cancers (non-small cell lung cancer, small cell lung cancer, nasopharyngeal cancer, head and neck cancer, melanoma, lymphoma) or recurrent/refractory blood cancers (acute myeloid leukemia, myelodysplastic syndromes). Another novel first-in-class immune checkpoint inhibitor from our lab will 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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