# The Role of the Microenvironment in Barrett's Esophagus

> **NIH NIH U54** · COLUMBIA UNIVERSITY HEALTH SCIENCES · 2022 · $441,975

## Abstract

PROJECT SUMMARY
Barrett’s esophagus is an increasingly prevalent, preneoplastic disorder resulting from acid/bile reflux and
chronic inflammation at the GE junction. The BETRNet Research Center 1 represents a translational research
program from Columbia University, the University of Pennsylvania and the Mayo Clinic. The team, which has
been highly productive, has been focused on the role of microbiota and the tumor microenvironment in the
development and progression of Barrett’s esophagus and esophageal adenocarcinoma. The group also includes
additional collaborative sites at MIT, the Dana Farber Cancer Institute and Munich Technical University, and
utilizes heavily a Microbiome and Metabolomics Core at Penn-CHOP. Thus, the team comprises broad and
unique expertise in mouse models, genomics, microbiology and clinical research. Our research program 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 utilizes both the novel
transgenic (L2-ILB) and innovative 3D organoid models, along with a cross-sectional study of 150 Barrett’s and
non-Barrett’s patients. Project 1 studied the role of microbiota and myeloid cells in the L2-ILB mouse model of
Barrett’s esophagus. This project incorporated germ-free housing, antibiotic eradication, colonization with
defined flora, myeloid cell ablation and correlative human studies. Project 2 focused on the characterization of
microenvironment drivers in BE, and included FACS/IHC analysis of CAFs and immune cells (MDSCs/Tregs) in
BE patients, along with 3D organoids in culture, as well as defining the role of IL-6 in response to epithelial TP53
mutations and immune cell activation. Finally, Project 3 seeks to identify novel biomarkers and gene signatures
related to the microbiome and microenvironment. The study analyzed 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. For the extension period, we propose
to continue and complete experiments and analyses related to the three Projects.

## Key facts

- **NIH application ID:** 10607819
- **Project number:** 3U54CA163004-10S1
- **Recipient organization:** COLUMBIA UNIVERSITY HEALTH SCIENCES
- **Principal Investigator:** Julian Abrams
- **Activity code:** U54 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $441,975
- **Award type:** 3
- **Project period:** 2022-05-01 → 2023-10-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10607819

## Citation

> US National Institutes of Health, RePORTER application 10607819, The Role of the Microenvironment in Barrett's Esophagus (3U54CA163004-10S1). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10607819. Licensed CC0.

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