# Pathways of Injury and Repair in Barrett's Carcinogenesis

> **NIH NIH P01** · CASE WESTERN RESERVE UNIVERSITY · 2024 · $2,111,965

## Abstract

PROGRAM SUMMARY
The central hypothesis of this program project is that “Altered squamous epithelial integrity (Prj 1) and
inflammatory injury (Prj 2) activate signaling pathways including EPHB2 (Prj 3) that affect precursor cells
at the squamocolumnar junction (SCj) transition, esophageal submucosal gland (ESMG), and basal
squamous niches, resulting in the alteration of regulatory factors that include Notch, Myc, p63, and
SOX9, leading to acinar ductal metaplasia (ADM), multi-layered epithelium (MLE), Barrett's esophagus
(BE), and ultimately esophageal adenocarcinoma (EAC).” The Specific Aims of our program are:
1) To elucidate signaling pathways by which mutated VSIG10L alters epithelial integrity leading to MLE and BE
like metaplasia on novel mouse models.
2) To define the spatial and temporal pattern of CXCL8 (IL-8) in ESMG following esophageal injury and
phenotype the inflammatory infiltrate that leads to the development of acinar ductal metaplasia (ADM) in ESMG
associated with BE/EAC.
3)To identify mediators of EPHB2 signaling that lead to c-MYC activation and metaplastic cellular differentiation
after injury in the development of BE and its progression to EAC.
4) To define how altered epithelial integrity, inflammatory cells, and alteration of signaling molecules that control
differentiation (EPHB2) lead to metaplasia by altering transcription factors.
5) Integrate projects by providing investigators effective support through Core resources with state-of-the-art
Biorepository, Bioinformatics, and Administrative Services.
These objectives build and synergize on the considerable clinical, basic science, and translational expertise
available at our institutions, 1) to focus laboratory research on understanding the genetic susceptibility and
molecular changes that influence the development of BE and EAC; and 2) to then translate laboratory discoveries
into clinical applications for effective detection, molecular risk stratification, and prevention of progression from
BE to EAC.

## Key facts

- **NIH application ID:** 10932155
- **Project number:** 5P01CA269019-02
- **Recipient organization:** CASE WESTERN RESERVE UNIVERSITY
- **Principal Investigator:** AMITABH CHAK
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $2,111,965
- **Award type:** 5
- **Project period:** 2023-09-20 → 2028-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10932155

## Citation

> US National Institutes of Health, RePORTER application 10932155, Pathways of Injury and Repair in Barrett's Carcinogenesis (5P01CA269019-02). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10932155. Licensed CC0.

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