# Investigating the role of mitochondria in Eosinophilic Esophagitis pathogenesis.

> **NIH NIH R01** · TEMPLE UNIV OF THE COMMONWEALTH · 2022 · $11,458

## Abstract

Project Summary
Eosinophilic Esophagitis (EoE) is a chronic type of food allergy whose pathobiology remains incompletely
understood. Damaging variants in the nuclear gene encoding the mitochondrial protein DHTKD1 have been
identified in EoE patients, indicating a potential role for mitochondria in EoE pathobiology. We have previously
reported that IL-13 induces autophagy flux as a cytoprotective mechanism in esophageal epithelium exposed
to EoE-relevant inflammatory stimuli. To extend these studies, we evaluated the impact of IL-13 upon
mitochondria, a well-established cellular target of autophagy. Unexpectedly, we found an increase in
mitochondria in esophageal keratinocytes treated with IL-13 rather than the hypothesized decrease. During her
rotation in my lab, Ms. Jackson (the current diversity supplement candidate) found that among EoE-relevant
cytokines IL-13 uniquely increased mitochondria in esophageal keratinocytes. She further demonstrated that
knockdown of the mitochondrial transcription factor TFAM partially restored squamous cell differentiation in IL-
13-treated esophageal organoids. Based upon these findings, we hypothesize that IL-13-mediated alterations
in mitochondrial biology contribute to impaired squamous cell differentiation in EoE. These studies will utilize
the experimental platforms and approaches developed during the parent R01 to explore this innovative
hypothesis. The Specific Aims of the current proposal are: Aim 1. To define the molecular mechanisms through
which IL-13 induces increased mitochondrial content in esophageal keratinocytes; and Aim 2. To elucidate the
functional role of mitochondria in EoE pathogenesis. Taken together, these studies will provide novel insight
into the role of mitochondria in EoE pathogenesis. Restoration of epithelial differentiation may promote
epithelial healing and barrier function in EoE patients, thereby limiting further antigen presentation. Thus,
findings from this study have potential for translational impact in EoE. The proposed studies will further provide
excellent training opportunities for Ms. Jackson as she develops novel conceptual and technical expertise
related to mitochondrial biology and formulated her F31 proposal.

## Key facts

- **NIH application ID:** 10516513
- **Project number:** 3R01DK121159-03S1
- **Recipient organization:** TEMPLE UNIV OF THE COMMONWEALTH
- **Principal Investigator:** Kelly A Whelan
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $11,458
- **Award type:** 3
- **Project period:** 2019-06-04 → 2024-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10516513

## Citation

> US National Institutes of Health, RePORTER application 10516513, Investigating the role of mitochondria in Eosinophilic Esophagitis pathogenesis. (3R01DK121159-03S1). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10516513. Licensed CC0.

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