# Dysregulation of Epithelial Metabolism and Regeneration by Sulfite Exposure in Pediatric Ulcerative Colitis

> **NIH NIH K99** · STANFORD UNIVERSITY · 2024 · $90,000

## Abstract

PROJECT SUMMARY
The prevalence of ulcerative colitis (UC) in children continues to increase yearly. Recent evidence in pediatric
UC patients showed significant mitochondrial impairment in the colon tissues. This is important as optimal
mitochondrial activity is required for the solemn function of colonic stem cells that replenish the physical barrier
of the colon epithelium. Since patients are constantly exposed to environmental factors such as diet, it is critical
to reveal the dietary factors that influence mitochondrial function in the colon epithelium as they would be vital in
the management of UC in children. Sulfites are endogenous products of several sulfur-containing compounds,
and they are also ubiquitous in our diets as preservatives. My preliminary data in colon organoids derived from
pediatric patients showed a detrimental role of sulfite on mitochondrial metabolism and differentiation, with worse
metabolic outcomes in samples from pediatric UC patients. My analysis of transcriptomic data from 206 children
with UC showed that the Mocs1 gene required for downstream clearance of sulfites in the mitochondria is
downregulated in the colon of UC patients, suggesting a potential for inefficient sulfite detoxification in the colon.
In this study, I will use patient-derived colon organoids to define how sulfites regulate mitochondrial metabolism
and differentiation in health and in UC (Aim 1), reveal the sulfite-induced and sulfite susceptibility chromatin sites
in the pediatric colon that explains these metabolic and differentiation anomalies (Aim 2), and how sulfites and
the loss of epithelial Mocs1 shape colon biology in the complex gut environment in vivo using physiological
relevant models (Aim 3). This award will advance my training in disease models of IBD, epithelial biology, and
epigenomics as I work toward establishing an innovative career in regenerative nutrition with a focus on pediatric
digestive diseases and continue efforts to enhance diverse representation in the biomedical sciences.

## Key facts

- **NIH application ID:** 10890146
- **Project number:** 5K99DK136971-02
- **Recipient organization:** STANFORD UNIVERSITY
- **Principal Investigator:** Babajide Ojo
- **Activity code:** K99 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $90,000
- **Award type:** 5
- **Project period:** 2023-08-01 → 2025-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10890146

## Citation

> US National Institutes of Health, RePORTER application 10890146, Dysregulation of Epithelial Metabolism and Regeneration by Sulfite Exposure in Pediatric Ulcerative Colitis (5K99DK136971-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10890146. Licensed CC0.

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