# Tissue remodeling in Eosinophilic Esophagitis: Discovery of novel pathways

> **NIH NIH R03** · UNIVERSITY OF COLORADO DENVER · 2020 · $116,625

## Abstract

PROJECT SUMMARY
This R03 project emerges directly from studies described in Dr. Menard-Katcher’s K23 award. The proposed
aims define a new direction of investigation within the broader goals of Dr. Menard-Katcher’s career
development that will provide essential data, critical skills and important collaborations. Together these will
provide a platform for R01 applications and complete research independence.
 Eosinophilic Esophagitis (EoE) is a chronic allergen mediated inflammatory esophageal disease with
substantial and increasing burden in children and adults. Chronic inflammation classically leads to dysphagia.
Mounting evidence identifies a subset of patients who develop clinically significant fibrosis and esophageal
stricture, a phenotype identified to have more severe symptoms and worse treatment response. Termed
fibrostenotic EoE (FS-EoE), this phenotype can be defined by partially occlusive stricture formation. Identifying
those patients at greatest risk of fibrosis; determining optimal management strategies; and closing gaps in our
understanding of the cellular pathways involved in the development of fibrotic disease are all needed to help
provide tailored approach to therapy. Supported by Dr. Menard-Katcher’s K23, we evaluated and characterized
over 110 pediatric EoE patients based on clinical outcomes, symptoms, endoscopic appearance, histology and
esophageal function (ie distensibility). RNASeq analysis from a subset of these patients identified genes with
altered expression that could define a FS-EoE phenotype. Gene pathway analysis identified SMAD protein
phosphorylation pathways to be differentially expressed between fibrotic (with stricture) and non-fibrotic
(without stricture) EoE subjects and specifically identified connective tissue growth factor (CTGF/CCN2)
overexpression in the FS-EoE phenotype.
 CTGF (or CCN2) is a secreted regulatory matricellular protein involved in promoting fibrosis often
through TGFß /SMAD in response to injury. CTGF is implicated in the progression of fibrosis in the kidney,
lung and skin and it may be an amenable target for treatment. We hypothesize CTGF is involved in promoting
fibrotic remodeling in EoE and that evaluation of the EoE proteome will identify novel proteins implicated in a
more severe fibrotic phenotype. To address this overarching hypothesis, we propose two related but
independent aims. As CTGF has not yet been explored in EoE or the esophagus, in Aim 1 we will determine
CTGF expression in in vitro and in a novel in vivo model of EoE. In Aim 2 we will evaluate the esophageal
mucosal proteome to identify targets and pathways implicated in the fibrostenotic phenotype.
 Results from the proposed Aims will elucidate if the CTGF pathway is implicated in EoE and use multi-
omic data to identify novel pathways and targets for next step research in the pathogenesis and possible
treatment of FS-EoE. This will provide novel evidence to support a successful R01 or similar application that
will in...

## Key facts

- **NIH application ID:** 10040535
- **Project number:** 1R03DK125638-01
- **Recipient organization:** UNIVERSITY OF COLORADO DENVER
- **Principal Investigator:** CALIES D Menard-Katcher
- **Activity code:** R03 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $116,625
- **Award type:** 1
- **Project period:** 2020-07-10 → 2022-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10040535

## Citation

> US National Institutes of Health, RePORTER application 10040535, Tissue remodeling in Eosinophilic Esophagitis: Discovery of novel pathways (1R03DK125638-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10040535. Licensed CC0.

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