# The Role of the Metaplastic Microenvironment in Barrett's Esophagus

> **NIH NIH R01** · COLUMBIA UNIVERSITY HEALTH SCIENCES · 2021 · $223,884

## Abstract

Project Summary
Esophageal Cancer is a leading cause of cancer death worldwide. The two subtypes include
Esophageal Squamous Cell Carcinoma (ESCC) and Esophageal Adenocarcinoma (EAC). In the
United States (US) and Western Europe, EAC is the more common subtype. In the US this year
over 16,000 individuals are expected to die from EAC. To improve survival, identification of its
precursor lesion, Barrett’s Esophagus is important. Barrett’s Esophagus, i.e. intestinal
metaplasia of the esophagus, occurs in the setting of chronic gastroesophageal reflux (GERD)
when the normal stratified squamous epithelium of the esophagus is replaced by an intestinal
type. Early Identification of this lesion leads to regular surveillance to monitor for progression to
dysplasia and adenocarcinoma. Some patients, however, never progress to EAC while others
do. Recently, in our lab we have identified that infiltrating fibroblasts and other immune cells
play an important role in promoting tumorigenesis. The role and phenotype of infiltrating
fibroblasts and other immune cells in promoting progression from metaplasia to dysplasia is
unclear. In this proposal we seek to clarify the role of the metaplastic microenvironment in
promoting this progression to dysplasia and adenocarcinoma. In particular, we seek to
understand how activated fibroblasts interact with the esophageal microbiome and deoxycholaic
acid in the gastro-esophageal refluxate. We hypothesize that specific, activated fibroblast
secrete pro-tumorigenic cytokines promoting progression to dysplasia in the context of
deoxycholic acid and altered esophageal microbiome induced by injury from gastro-esophageal
refluxate. This hypothesis will be pursued through the following inter-related specific aims: 1.)
To assess the effect of DCA on Barrett’s Esophagus Associated Fibroblasts and 2.) To assess
the effect of Enterobacteriaceae on Barrett’s Esophagus Associated Fibroblasts. The parent
grant addresses the hypothesis that deoxycholic acid (DCA) in gastro-esophageal refluxate
induces Notch signaling in BE, decreasing goblet cell differentiation and mucus production. This
in turn increases the interaction of pro-carcinogenic bacteria with the underlying epithelium,
promoting the development of EAC. However, the parent R01 does not address the relationship
between DCA, Notch signaling, and the microbiome with the BE-associated microenvironment.
This proposal address this critical gap.

## Key facts

- **NIH application ID:** 10381174
- **Project number:** 3R01CA255298-01S1
- **Recipient organization:** COLUMBIA UNIVERSITY HEALTH SCIENCES
- **Principal Investigator:** Julian Abrams
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $223,884
- **Award type:** 3
- **Project period:** 2021-01-01 → 2025-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10381174

## Citation

> US National Institutes of Health, RePORTER application 10381174, The Role of the Metaplastic Microenvironment in Barrett's Esophagus (3R01CA255298-01S1). Retrieved via AI Analytics 2026-05-28 from https://api.ai-analytics.org/grant/nih/10381174. Licensed CC0.

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