# High-throughput functional analyses of the genetic drivers of Inflammatory Bowel Disease

> **NIH NIH R01** · BAYLOR COLLEGE OF MEDICINE · 2024 · $233,600

## Abstract

Inflammatory Bowel Disease (IBD) is a debilitating condition characterized by chronic inflammation, leading to
the erosion of essential intestinal functions. The risk of developing IBD, including related diseases like Crohn's
and ulcerative colitis, involves a complex interplay of over 250 genetic and environmental factors. Dysbiosis of
the gut microbiome and pathogen proliferation often worsen the disease pathophysiology. While some
common genetic risk factors, especially those related to the immune system, are well understood, the
functional contributions of most risk alleles remain unclear. Moreover, the majority of known genetic risk factors
have been identified in European ancestry populations, which may not translate to more diverse populations.
Our long-term goal is to gain a comprehensive understanding of the genetic risk factors contributing to IBD
development. We hypothesize that genetic alterations in intestinal gene function create conditions for
persistent dysbiosis and inflammation, driving IBD. To achieve this, we have established a robust cross-
organismal platform for high-throughput functional profiling of IBD candidate genes, advancing our
understanding of the disease's mechanisms.
We aim to address our hypothesis through two specific aims: 1) conducting high-throughput screening and
phenotypic characterization of IBD risk genes in C. elegans, a nematode microbiome model; and 2) validating
IBD risk alleles in human intestinal organoids (HIOs). Importantly, our research will encompass and integrate
risk alleles from diverse populations, providing a more comprehensive assessment of IBD risk. This study is
significant because it delves into the functional profiling of IBD risk genes at the organismal level, a less-
explored area. Further, it extends its focus to diverse multi-ancestry cohorts, filling a critical gap in
understanding of the disease. The platform developed also has the potential to be used in studying other
microbiome-mediated diseases. Ultimately, this work can enhance our understanding of the genetic
landscapes of IBD, offering both broad functional testing and specific mechanistic insights, which are vital for
the diagnosis and treatment of this prevalent digestive disease.

## Key facts

- **NIH application ID:** 10983491
- **Project number:** 1R01DK140907-01
- **Recipient organization:** BAYLOR COLLEGE OF MEDICINE
- **Principal Investigator:** SARAH E BLUTT
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $233,600
- **Award type:** 1
- **Project period:** 2024-09-01 → 2027-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10983491

## Citation

> US National Institutes of Health, RePORTER application 10983491, High-throughput functional analyses of the genetic drivers of Inflammatory Bowel Disease (1R01DK140907-01). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10983491. Licensed CC0.

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