# The Role of the Microenvironment in Barrett's Esophagus

> **NIH NIH U54** · COLUMBIA UNIVERSITY HEALTH SCIENCES · 2020 · $802,412

## Abstract

OVERALL PROJECT SUMMARY
Barrett’s esophagus is an increasingly prevalent, preneoplastic disorder resulting from acid/bile reflux and
chronic inflammation at the GE junction. This application is a renewal of a long-standing multicenter,
translational research program from Columbia University, the University of Pennsylvania and the Mayo Clinic.
The team, which has been highly productive, will now focus on the role of microbiota and the tumor
microenvironment in the development and progression of Barrett’s esophagus and esophageal
adenocarcinoma. The group has added additional collaborative sites at MIT, the Dana Farber Cancer Institute
and Munich Technical University, and will utilize heavily a new Microbiome and Metabolomics Core at Penn-
CHOP. Thus, the team comprises broad and unique expertise in mouse models, genomics, microbiology and
clinical research. The application is built around the hypothesis that the inflammation-dependent tumor
microenvironment, modulated by the GE junction microbiome, is critical for early progression of esophageal
carcinogenesis. The proposal will utilize both the novel transgenic (L2-IL-1β) and innovative 3D organoid
models, along with a cross-sectional study of 100 BE patients. Project 1 will study the role of microbiota and
myeloid cells in the L2-IL-1β mouse model of Barrett’s esophagus. This project will incorporate germ-free
housing, antibiotic eradication, colonization with defined flora, myeloid cell ablation and correlative human
studies. Project 2 is focused on the characterization of microenvironment drivers in BE, and will include
FACS/IHC analysis of CAFs and immune cells (MDSCs/Tregs) in BE patients, along with 3D organoids in
culture. The role of IL-6 in response to epithelial TP53 mutations and immune cell activation will be defined.
Finally, Project 3 will seek to identify novel biomarkers and gene signatures related to the microbiome and
microenvironment. The study will analyze bile acids, a product of microbes, and minimally invasive tests such
as saliva/breath test/tethered capsule sponge to analyze microbes to develop screening/surveillance
strategies. Overall, these projects will advance the science of the microbiome and microenvironment in BE that
will hopefully lead to translational applications.

## Key facts

- **NIH application ID:** 9956592
- **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:** $802,412
- **Award type:** 5
- **Project period:** 2011-09-26 → 2022-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9956592

## Citation

> US National Institutes of Health, RePORTER application 9956592, The Role of the Microenvironment in Barrett's Esophagus (5U54CA163004-09). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9956592. Licensed CC0.

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