Jun Wang
New York University, NY·Microbiology & Immunology
Drugs that release the brakes on the immune system, called immune checkpoint inhibitors, have changed cancer treatment. The best known block PD-1, a receptor on T cells (the immune cells that kill tumor cells), or its partner PD-L1.
- Fields
Microbiology & Immunology
Medicine & Clinical Research
Biochemistry
- Topics
cancer immunotherapy
immune checkpoint
Siglec-15
- Grants
- 2 known grants, through Nov 2027
What they work on
- Determine whether Siglec-15, a tumor-associated immune brake, also suppresses myeloid cells such as macrophages, and identify the receptors it binds on myeloid cells and T cells.
- Test whether cancer-driving KRAS mutations switch on Siglec-15 in cancer cells, and find better anti-Siglec-15 drug combinations using mouse models of pancreatic and ovarian cancer that carry KRAS mutations.
- Determine how FGL1 made by tumors, a partner protein for the T-cell brake LAG-3, affects anti-tumor immunity, whether KRAS mutations induce it, and whether its levels predict immunotherapy response.
- Compare in-house anti-LAG-3 antibodies that block FGL1 binding, MHC-II binding, or both for their anti-tumor effects, and map where they bind on LAG-3 using cryo-electron microscopy and X-ray crystallography.
More about the research
Yet most patients do not get a lasting response, and many tumors make no PD-L1 at all. The research described here looks for other molecular brakes that tumors use to switch off immune attack. It then works out how those brakes act, so that new antibody therapies can be designed and matched to the right patients. Two projects pursue two such brakes: Siglec-15 and the FGL1–LAG-3 pair.
Why it matters
Many people with cancer do not respond to PD-1/PD-L1 drugs, especially when their tumors lack PD-L1. This work could improve Siglec-15 antibody therapy, which is already in clinical trials for PD-1-resistant metastatic solid cancers. It could also guide the design of better LAG-3-blocking antibodies and combination treatments. Blood FGL1 levels may become a biomarker that helps doctors choose which patients are likely to benefit from immunotherapy, for example in lung cancer and melanoma.
Known grants
From NIH and NSF research grants. Labs often have other funding we can't see.
Closest labs
David Tweardy
University of Texas MD Anderson Cancer Center, TX·Medicine & Clinical Research
Determine whether the STAT3 inhibitor TTI-101, alone or combined with anti-PD-1 antibody, treats lung tumors effectively in the K-ras mutant CC-LR mouse model of non-small cell lung cancer.
Drew Pardoll
Johns Hopkins University, MD·Microbiology & Immunology
Identify molecules made by regulatory T cells (Tregs), immune cells that suppress other immune cells, that are found specifically in tumors of patients who do not respond to anti-PD-1 or anti-PD-L1 therapy.
Masanobu Komatsu
Johns Hopkins University, MD·Microbiology & Immunology
Test whether the signaling protein R-Ras in blood vessel cells drives the formation of high endothelial venules in tumors, using mice that lack or overproduce endothelial R-Ras in mammary tumor and melanoma models.
The school
New York University: 72 labs on PI Pages, $1.5B a year on research, 540 research doctorates a year.
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