Gabor J Tigyi
University of Tennessee Health Science Center, TN·Pharmacology
Tumors often survive because the immune cells that should destroy them get switched off. One brake on those killer cells is a receptor called LPAR5 (lysophosphatidic acid receptor subtype 5), a protein on the surface of CD8 cytotoxic T lymphocytes — the white blood cells that recognize and kill tumor cells.
- Fields
Pharmacology
Microbiology & Immunology
Chemistry
- Topics
lysophosphatidic acid
immune checkpoint
cytotoxic T lymphocytes
- Grants
- 1 known grant, through Jul 2027
What they work on
- Optimize small-molecule antagonists of the LPAR5 receptor from existing screening hits, using computational scaffold hopping and a pharmacophore model that maps the chemical features needed for potent, selective binding.
- Determine how selective the new compounds are, testing them against the other lysophosphatidic acid receptor subtypes and against autotaxin, the enzyme that produces lysophosphatidic acid.
- Rank antagonists by how strongly they restore antigen-specific T-cell receptor activation and interleukin-2 production by CD8 T cells in the presence of lysophosphatidic acid.
- Advance roughly eight compounds through cell assays and three through pharmacokinetic and toxicity testing, then measure whether the leads boost tumor killing in mouse and human cell assays and reduce B16 melanoma metastasis in mice.
More about the research
LPAR5 is switched on by lysophosphatidic acid, a small fat-like signaling molecule that is abundant in the body and especially around tumors. This project asks whether blocking that receptor with a drug can release the brake and restore tumor killing.
Why it matters
Many cancers escape treatment by shutting down the immune system's killer T cells. A drug that blocks the LPAR5 receptor could act as a new kind of immune checkpoint inhibitor, re-energizing anti-tumor immunity in patients whose cancers resist existing immunotherapies. The project's concrete output is a nominated lead compound and backup chemical series ready for preclinical development.
Known grants
From NIH and NSF research grants. Labs often have other funding we can't see.
Closest labs
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Design and synthesize new compounds based on screening hits to explore the structure–activity relationships of hydroxyproline dehydrogenase (HYPDH) inhibitor scaffolds, improving potency, selectivity and drug-like properties.
The school
University of Tennessee Health Science Center: 4 labs on PI Pages, $125M a year on research, 197 research doctorates a year.
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