# Signaling Mechanisms Promoting Barrett’s Metaplasia

> **NIH NIH R01** · COLUMBIA UNIVERSITY HEALTH SCIENCES · 2021 · $436,739

## Abstract

PROJECT SUMMARY
Barrett’s esophagus (BE) is the only known pre-cancer lesion of esophageal adenocarcinoma (EAC) which has
seen a 600% increase in incidence. However, the cellular and molecular mechanism driving BE initiation and
progression remains undetermined, and the knowledge gap prevents us from identifying meaningful therapeutic
targets for the treatment of the pathological entity. This application will build on our recent findings that the novel
transitional basal stem cells contribute to Barrett’s metaplasia in both mouse genetics and human organoid
models. We will study the molecular mechanism promoting the intestinal differentiation of the unique stem cell
population. Our preliminary data suggest that Wnt signaling and its downstream target SOX4 play critical roles
in the pathogenesis of BE. Therefore we will test the hypothesis that the Wnt/SOX4 axis promotes Barrett’s
metaplasia and that pharmacological inhibition of the axis blocks BE progression. We have designed three aims
to test this hypothesis: (1) To test the hypothesis that increased Wnt signaling upon chronic inflammation
promotes Barrett’s metaplasia of transitional basal stem cells. (2) To test the hypothesis that SOX4 mediates
Wnt signaling to promote Barrett’s metaplasia, and (3) To intervene in the Wnt/SOX4 axis for therapeutic gain
against BE and EAC. We will use multiple mouse models (e.g. Wnt and SOX4 gain- and loss-of-function)
combined with organoid and in vitro assays to address these aims and test candidate drugs identified through
an unbiased screen. This work will provide novel insights into the cellular and molecular mechanisms underlying
the initiation and progression of BE, and the signaling program we identified will enable discovery of new
therapeutic targets.

## Key facts

- **NIH application ID:** 10129373
- **Project number:** 5R01DK120650-03
- **Recipient organization:** COLUMBIA UNIVERSITY HEALTH SCIENCES
- **Principal Investigator:** Jianwen Que
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $436,739
- **Award type:** 5
- **Project period:** 2019-05-20 → 2023-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10129373

## Citation

> US National Institutes of Health, RePORTER application 10129373, Signaling Mechanisms Promoting Barrett’s Metaplasia (5R01DK120650-03). Retrieved via AI Analytics 2026-06-11 from https://api.ai-analytics.org/grant/nih/10129373. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*