# Inflammation And Submucosal Glands During Esophageal Injury And Repair

> **NIH NIH P01** · CASE WESTERN RESERVE UNIVERSITY · 2024 · $601,859

## Abstract

PROJECT SUMMARY
The etiology of Barrett's esophagus (BE), a complex metaplastic disorder of the distal esophagus, remains
elusive. Patients with BE are at an increased risk of developing esophageal adenocarcinoma (EAC), a lethal,
and increasingly prevalent disease, and the most common esophageal malignancy in the U.S. Our long-term
objective is to identify the causative mechanisms underlying the onset and malignant progression of BE, and to
develop evidence-based biomarkers and chemopreventive/therapeutic strategies for subsequent clinical
intervention. Project 2 of this program addresses a controversial area in the field that has been understudied.
Esophageal submucosal glands (ESMGs) represent a progenitor cell source in the esophagus and our group
has previously demonstrated increased proliferation and acinar ductal metaplasia (ADM) in ESMGs in the
context of injury and EAC. We have observed immune cell infiltrates in ESMGs associated with ADM, but
important knowledge gaps persist about the types of immune cells found in areas of ADM and the effect of this
microenvironment on ADM, wound healing, and the molecular programs associated with BE/EAC. Project 2 will
thus investigate the relationship between injury-induced cytokines such as C-X-C motif chemokine ligand 8
(CXCL8 or IL8)), esophageal wound healing, and ADM. Ongoing inflammation and abnormal signaling in ESMGs
and at the GEJ may provide a persistent source of abnormal progenitor cells after radiofrequency ablation,
contributing to treatment failures including refractory and recurrent dysplasia and progression to EAC. The
proposed project will address preclinical questions about how to improve outcomes after radiofrequency ablation
or endoscopic resection of early lesions, including high grade dysplasia and very early cancers. To address
these research questions, we will use our 1) large human esophagectomy database that includes failed-
radiofrequency ablation cases that resulted in esophagectomy, and 2) our porcine radiofrequency ablation model
and porcine and patient-derived organoids. Our project has strong synergy with both projects 1 and 3, expanding
the scope our program project grant to include models with ESMGs and allowing comparison to wound healing
at the gastroesophageal junction. We will investigate how targeting the inflammation in ESMGs and at the
gastroesophageal junction may provide a potential cancer interception and preventive strategies.
.

## Key facts

- **NIH application ID:** 10932161
- **Project number:** 5P01CA269019-02
- **Recipient organization:** CASE WESTERN RESERVE UNIVERSITY
- **Principal Investigator:** Katherine Garman
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $601,859
- **Award type:** 5
- **Project period:** 2023-09-20 → 2028-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10932161

## Citation

> US National Institutes of Health, RePORTER application 10932161, Inflammation And Submucosal Glands During Esophageal Injury And Repair (5P01CA269019-02). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10932161. Licensed CC0.

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