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Investigating the Role of GZMA-Producing Tissue-Resident Memory Th17 Cells in Inflammatory Bowel Disease

Award Number: F31AI200197
ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS
PERIOD OF PERFORMANCE START DATE: 12/04/2026
PERIOD OF PERFORMANCE END DATE: 12/03/2027

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Investigating the Role of GZMA-Producing Tissue-Resident Memory Th17 Cells in Inflammatory Bowel Disease - ABSTRACT Inflammatory Bowel Disease (IBD), which includes Crohn’s disease and ulcerative colitis, affects more than 3 million individuals in the United States. It is marked by relapsing intestinal inflammation, epithelial barrier dysfunction, and long-term tissue damage. Despite progress in immunosuppressive therapies, many patients remain refractory to treatment or experience recurrent flares, underscoring the urgent need for new mechanistic insights and targeted interventions. This proposal investigates a newly identified population of CD4⁺ tissue- resident memory Th17 (Trm17) cells that express granzyme A (GZMA), a cytotoxic effector molecule typically associated with CD8⁺ T cells and NK cells. Preliminary data from human IBD tissues reveal that GZMA is highly enriched in Trm cells at sites of epithelial barrier loss. In murine models of colitis, Trm17 cells exhibit selective GZMA expression, distinguishing them from other T cell populations that express granzyme B or IFN-γ. These findings support a model in which Trm17-derived GZMA drives epithelial damage and sustains chronic inflammation. Aim 1 will define the functional contribution of GZMA to disease using antibody depletion and conditional knockout mice targeting GZMA in CD103⁺ Trm cells. Aim 2 will identify transcriptional regulators of GZMA using single-cell RNA sequencing and in vivo CRISPR screening, followed by validation in genetic knockout models. Outcomes will assess epithelial integrity, inflammation, and clinical disease severity. This project integrates advanced immunological techniques, spatial and single-cell transcriptomics, gene editing, and in vivo models to dissect a novel cytotoxic pathway in CD4⁺ T cells. It is among the first to mechanistically explore the effector functions of Trm17 cells in IBD and could uncover new therapeutic targets. The findings may also provide broader insight into tissue-resident T cell behavior in other chronic inflammatory conditions. The applicant brings a unique interdisciplinary background in biomedical engineering and computational biology, which enhances his ability to bridge bench science with high-dimensional data analysis. Through this fellowship, the applicant will gain hands-on experience in flow cytometry, T cell functional assays, spatial transcriptomics, CRISPR screening, and colitis models. He will receive mentorship from a multidisciplinary team with expertise in mucosal immunology, T cell biology, and transcriptomic data interpretation. Training will be reinforced through formal coursework, workshops in scientific communication and grant writing, and peer mentoring activities. The MMI program at USC provides a highly collaborative, well-resourced environment for advanced graduate training. This fellowship will prepare the applicant for a successful academic career as an independent investigator focused on translational immunology and inflammatory disease.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2026 ( Subtotal = $50,114 )
2026	2026	UNIVERSITY OF SOUTHERN CALIFORNIA	3720 S FLOWER ST FL 3	LOS ANGELES	CA	90089	LOS ANGELES	USA	Allergy and Infectious Diseases Research	000	1	6/8/2026	NEW	$50,114
														Subtotal = $50,114

Grand Total All Awards = $50,114

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Investigating the Role of GZMA-Producing Tissue-Resident Memory Th17 Cells in Inflammatory Bowel Disease

Award Number: F31AI200197

ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS

PERIOD OF PERFORMANCE START DATE: 12/04/2026

PERIOD OF PERFORMANCE END DATE: 12/03/2027

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