# Project 2: Characterization of microenvironmental drivers of neoplasia in BE

> **NIH NIH U54** · COLUMBIA UNIVERSITY HEALTH SCIENCES · 2020 · $198,070

## Abstract

PROJECT SUMMARY 
Barrett’s esophagus (BE) is the replacement of the normal squamous esophageal epithelium with an 
incompletely intestinalized columnar epithelium. It occurs in response to chronic acid and bile reflux injury to 
the esophagus and is the most substantial risk factor for esophageal adenocarcinoma (EAC), a disease whose 
incidence has risen at an alarming rate. Therefore, improving our understanding of the pathogenesis of BE 
and its progression to EAC is a critical research imperative. A key lesson of recent genomic studies led in part 
by this team has demonstrated that many potentially pathogenic somatic mutations are present in the BE 
epithelium of those who do not progress to dysplasia or cancer, highlighting the important role of processes 
other than genomic mutations for promoting disease onset and progression. Here, we focus on the pivotal role 
of the tumor microenvironment in the pathogenesis of BE and EAC pathogenesis through aims that are 
integrated and complementary. We provide new and compelling data implicating a subset of infiltrating 
activated fibroblasts and immune cells in an interconnected web of mutually reinforcing signaling pathways 
with BE epithelial cells that enhances carcinogenesis. We hypothesize that these tumor-promoting cell 
populations in the BE microenvironment are key to understanding how and why BE progresses to EAC and 
that characterization of these cells and regulatory pathways will serve as a foundation for developing 
new approaches for screening and therapeutics. This hypothesis will be pursued through the following 
inter-related Specific Aims: 1) To determine the nature and function of the immune cells and fibroblasts 
present in human BE and EAC patients. 2) To demonstrate how IL-6 secreted by cancer associated 
fibroblasts and TP53 mutant epithelium promotes BE pathogenesis and progression to EAC. 3) To examine 
the effect of Myeloid-Derived Suppressor Cells (MDSC) and regulatory T-cells (TReg) on the progression of BE 
to EAC. Summary and

## Key facts

- **NIH application ID:** 9956607
- **Project number:** 5U54CA163004-09
- **Recipient organization:** COLUMBIA UNIVERSITY HEALTH SCIENCES
- **Principal Investigator:** Anil K Rustgi
- **Activity code:** U54 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $198,070
- **Award type:** 5
- **Project period:** — → —

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9956607

## Citation

> US National Institutes of Health, RePORTER application 9956607, Project 2: Characterization of microenvironmental drivers of neoplasia in BE (5U54CA163004-09). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9956607. Licensed CC0.

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