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Characterizing Antigen Presentation and Adaptive Immunity in Inflammatory Bowel Disease

Award Number: F30DK145200
ORGANIZATION: NATIONAL INSTITUTE OF DIABETES & DIGESTIVE & KIDNEY DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS
PERIOD OF PERFORMANCE START DATE: 04/01/2026
PERIOD OF PERFORMANCE END DATE: 03/31/2031

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Characterizing Antigen Presentation and Adaptive Immunity in Inflammatory Bowel Disease - Project Summary/Abstract: Inflammatory bowel disease (IBD) is a chronic inflammatory process initiated in the intestinal mucosa, typically onset in young adults. IBD causes severe morbidity and emergent complications often necessitating surgery, with a high proportion of IBD patients relapsing or being unresponsive to anti-TNF therapy. Despite the urgent clinical need for improved IBD treatments, pathophysiology of IBD remains incompletely understood, thought to result from complex genetic and environmental factors. Abnormalities in adaptive and innate immunity, cellular and ER stress, increased mucosal barrier permeability, dysbiosis, and genetic variants in autophagy and immune signaling components may contribute to increasingly pro-inflammatory gut immune dynamics, ultimately spreading to extra-intestinal manifestations in almost half of patients. Adaptive immunity, especially the Th17 T-cell subset converting to a pro-inflammatory phenotype, has been widely accepted as an important proponent of inflammation in IBD, with specific microbial strains and viral integration implicated as possible drivers. However, the antigen presentation landscape of T-cell epitopes has never been systematically characterized. In this research effort, we will profile antigen presentation by experimental immunopeptidomics, then computationally prioritize these HLA-presented peptides for immunogenicity, also examining molecular mimicry with self-antigens, to more deeply understand IBD pathophysiology (Aim 1). Adaptive immune responses can be triggered by ER stress, a biochemically complex phenomenon whose far-reaching role in IBD contributes to numerous pathologic features. Since evidence shows ER stress alters antigen presentation, we will attempt to draw a mechanistic link in the context of IBD, resolving specific antigen presentation changes induced by ER stress (Aim 2). Finally, we will attempt to validate immunogenicity of peptide epitopes by detecting antigen-specific T-cell receptors. Combining the abundant IBD resources in our biobanks and IBD Center with the expertise of an experienced, interdisciplinary team, we will endeavor to answer these important questions about adaptive immunity in IBD, while creating a high-quality dataset that lays the groundwork for future studies.


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 = $54,538 )
2026	2026	TRUSTEES OF THE UNIVERSITY OF PENNSYLVANIA, THE	3451 WALNUT ST	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	1	3/27/2026	NEW	$54,538
2026	2026	TRUSTEES OF THE UNIVERSITY OF PENNSYLVANIA, THE	3451 WALNUT ST	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	001	1	3/27/2026	NEW	$0
														Subtotal = $54,538

Grand Total All Awards = $54,538

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Characterizing Antigen Presentation and Adaptive Immunity in Inflammatory Bowel Disease

Award Number: F30DK145200

ORGANIZATION: NATIONAL INSTITUTE OF DIABETES & DIGESTIVE & KIDNEY DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS

PERIOD OF PERFORMANCE START DATE: 04/01/2026

PERIOD OF PERFORMANCE END DATE: 03/31/2031

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