# Using human intestinal organoids to model IBD pathogenesis

> **NIH NIH R21** · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · 2021 · $242,250

## Abstract

ABSTRACT
Inflammatory bowel disease (IBD) is a chronic disease characterized by intermittent episodes of intestinal
inflammation and disruption of the intestinal epithelial barrier. The IBD Genetics Consortium has intensively
studied the genetic architecture of this complex disease. Assigning molecular mechanisms to IBD risk variants
is critical to understanding disease etiology and for identification of new drug targets. Human genetics has the
potential to provide an unbiased view of the causative disease mechanisms. IBD already has been the subject
of intensive genetic investigations, including genome-wide association studies (GWAS) that have uncovered
dozens of risk loci. However, mechanistic understanding of these risk loci has been a challenge, and in this
exploratory R21 proposal, we will employ two functional models – patient-derived enteroids and human intestinal
organoids (HIOs) – to study the role of several important genes in epithelial restitution during IBD. This project
depends on close collaboration with the NIDDK IBD Genetics Consortium (IBDGC) for two reasons. First, we
will benefit from early access to IBDGC data to ensure that we deploy our pipeline for functional characterization
of the highest priority IBD risk variants. Second, we will access patient-derived enteroids as a collaboration with
the IBDGC. Our central goal is functional characterization of the biological pathways disrupted by IBD risk
variants, which we will accomplish with two specific aims. In Aim 1, we will use gene editing to delete genetic
loci, produce HIOs, and study developmental role of genes of interest. In Aim 2, we will investigate the
contribution of specific genetic loci to intestinal dysfunction in proliferation, epithelial barrier integrity, autophagy,
cellular stress, and regenerative ability using patient-derived enteroids and gene-edited HIOs.

## Key facts

- **NIH application ID:** 10264945
- **Project number:** 5R21DK127206-02
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
- **Principal Investigator:** Ophir D Klein
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $242,250
- **Award type:** 5
- **Project period:** 2020-09-16 → 2022-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10264945

## Citation

> US National Institutes of Health, RePORTER application 10264945, Using human intestinal organoids to model IBD pathogenesis (5R21DK127206-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10264945. Licensed CC0.

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