# Intestinal Stem Cell Metabolism in Inflammatory Bowel Disease Mucosal Healing

> **NIH NIH F32** · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · 2024 · $91,432

## Abstract

Project Summary/Abstract
Inflammatory bowel disease (IBD), including ulcerative colitis and Crohn’s disease, is a complex disease
that results in long-term inflammation within the intestine. Approximately 3.1 million individuals in the United
States are currently living with IBD with 70,000 newly identified cases each year. This presents a significant
financial burden on individuals and the economy, costing over $14.6 billion annually in the United States.
Patients with IBD experience cycles of inflammation and tissue damage followed by periods of repair and
remission. The majority of immunotherapies for IBD treatment have been focused on modifying the immune
response, which are highly effective, but nearly a third of patients relapse within 12 months. Redirecting our
focus on how the mucosa is repaired will likely provide an added benefit in IBD treatment when coupled with
immune modulating therapies. The unique ability of intestinal stem cells (ISCs) to self-renew and
differentiate into functional epithelial cells makes them an indispensable component of tissue repair. In the
gut, different populations of damage-associated ISCs exist, including a ISC population that emerges during
colitis-associated inflammation. To better understand this population, we developed a 3-D murine organoid
model system that enriches for these cells. This system will be utilized to study how cell metabolism impacts
the reparative function of colitis-associated ISCs. The use of metabolite analysis via mass spectrometry and
metabolic bioenergetic analysis using a Seahorse XFe96 Analyzer will allow us to generate a metabolic
profile for these cells. We are also developing a novel mouse reporter line to study how glucose
transporters impact the reparative function of colitis-associated ISCs in an intestinal injury-repair model of
inflammation. Successful completion of this grant will allow us to better understand how the cell metabolism
of colitis-associated ISCs impacts mucosal healing. Our long-term goal is to identify biomarkers of colitis-
associated ISCs to define mucosal healing and disease remission more accurately. A better understanding
of the molecular processes that influence colitis-associated ISC function will encourage the development of
novel therapeutics that help to regenerate the damaged epithelium. This work is being conducted at the
Rangos Research Center of UPMC Children’s Hospital of Pittsburgh and the University of Pittsburgh, which
is an outstanding research environment that provides the trainee with the physical resources, research
cohorts, and intellectual resources to successful complete this work. The detailed training plan designed will
help develop the trainee’s scientific expertise in ISC metabolism, biomarker discovery, and IBD, and
facilitate the transition into an independent investigator in IBD research.

## Key facts

- **NIH application ID:** 10932840
- **Project number:** 5F32DK132826-02
- **Recipient organization:** UNIVERSITY OF PITTSBURGH AT PITTSBURGH
- **Principal Investigator:** Heather Mentrup
- **Activity code:** F32 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $91,432
- **Award type:** 5
- **Project period:** 2023-08-10 → 2026-08-09

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10932840

## Citation

> US National Institutes of Health, RePORTER application 10932840, Intestinal Stem Cell Metabolism in Inflammatory Bowel Disease Mucosal Healing (5F32DK132826-02). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10932840. Licensed CC0.

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