Tuesday, April 1, 2025 4/1/2025

Using molecular quantitative trait loci mapping approaches to determine candidate gene regulatory mechanisms of functional variants within inflammatory bowel disease GWAS loci.

Award Number: F31DK137574
ORGANIZATION: NATIONAL INSTITUTE OF DIABETES & DIGESTIVE & KIDNEY DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS

Group Awards By:

View Award Description

Using molecular quantitative trait loci mapping approaches to determine candidate gene regulatory mechanisms of functional variants within inflammatory bowel disease GWAS loci. - 1 PROJECT SUMMARY/ABSTRACT 2 3 Inflammatory bowel diseases (IBDs) such as Crohn’s disease and ulcerative colitis are chronic inflammatory 4 disorders that cause damage to the gastrointestinal tract. There is no cure for IBD. Current therapies treat 5 inflammatory responses but do not target underlying causes. Research improving our understanding of 6 underlying causes of IBD can lead to improved treatment of disease. The intestinal epithelial barrier plays a 7 critical role in the development of chronic intestinal inflammation. There is increasing evidence that barrier 8 function and immune responses in IBD are influenced by genetic factors and confer disease risk. While over 200 9 genomic loci have been associated with IBD by genome-wide association studies (GWAS), only a handful of 10 these loci have known molecular mechanisms. Loci falling within non-coding regions suggests variants perturb 11 regulatory mechanisms by altering transcription factor binding and local chromatin structure but identifying exact 12 mechanisms and target genes remains challenging using GWAS alone. Mapping molecular quantitative trait loci 13 associate traits such as gene expression (eQTL) and chromatin accessibility (caQTL) with genetic variants, 14 provides evidence to functionally link variants to regulatory mechanisms and target genes. Mapping QTL in 15 diseased tissue specifically will identify regulatory mechanisms active in disease. I hypothesize that using a 16 QTL approach in colonic mucosa can reveal functional IBD variants and their regulatory mechanisms that may 17 be altered in the presence of disease. In Aim 1 I will map eQTL in IBD colon tissue to identify putative target 18 genes of IBD GWAS loci. In Aim 2 I will map caQTL in colon tissue to identify functional variants within regulatory 19 elements that may modulate expression of target genes by altering binding of transcription factors. In Aim 3 I will 20 determine the functional consequences of altered expression of CAMK2A, a putative IBD GWAS target gene, 21 on intestinal epithelial barrier function. Together, these aims will increase our understanding of the molecular 22 pathogenesis of IBD by uncovering previously unidentified regulatory mechanisms and target genes of IBD- 23 associated variants and provide novel biomarkers or candidates for therapeutic targets. This proposal seeks to 24 leverage the rigorous coursework, computational resources, collaborative environment, curated mentorship, and 25 access to clinical samples available at the University of North Carolina at Chapel Hill to provide the best possible 26 Ph.D. training in Bioinformatics and Computational Biology. This project will not only elucidate the functional role 27 of variants contributing to the molecular pathophysiology of IBD but will also provide the valuable experience 28 and training necessary for a career as an independent research investigator.


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: 2025 ( Subtotal = $42,574 )
2025	2025	UNIVERSITY OF NORTH CAROLINA AT CHAPEL HILL	104 AIRPORT DR STE 2200	CHAPEL HILL	NC	27599	ORANGE	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	2	2/14/2025	NON-COMPETING CONTINUATION	$42,574
														Subtotal = $42,574

Issue Date FY: 2024 ( Subtotal = $42,574 )
2024	2024	UNIVERSITY OF NORTH CAROLINA AT CHAPEL HILL	104 AIRPORT DR STE 2200	CHAPEL HILL	NC	27599	ORANGE	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	001	1	5/2/2024	NEW	$1,280
2024	2024	UNIVERSITY OF NORTH CAROLINA AT CHAPEL HILL	104 AIRPORT DR STE 2200	CHAPEL HILL	NC	27599	ORANGE	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	1	2/14/2024	NEW	$41,294
														Subtotal = $42,574

Grand Total All Awards = $85,148

Top

All Categories

About

Search

Reports

Data Submission

Award Information

Using molecular quantitative trait loci mapping approaches to determine candidate gene regulatory mechanisms of functional variants within inflammatory bowel disease GWAS loci.

Award Number: F31DK137574

ORGANIZATION: NATIONAL INSTITUTE OF DIABETES & DIGESTIVE & KIDNEY DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer