# Elucidating the mechanisms by which the extracellular matrix contribute to gastroesophageal cancer pathobiology

> **NIH NIH R01** · COLUMBIA UNIVERSITY HEALTH SCIENCES · 2024 · $15,925

## Abstract

ABSTRACT
Gastric cancer (GC), the third leading cause of cancer death worldwide, is characterized both by
histologic and molecular criteria. The two most common forms include Diffuse GC (DGC) and
Intestinal GC (IGC). Each class of GC is associated with early inactivation of a distinct tumor
suppressor, DGC with CDH1 (encoding E-cadherin) and IGC with p53. Beyond genetic changes,
gastric cancer development is promoted by environmental factors, specifically Helicobacter
infection and exposure to dietary nitrates. We posit that addressing two fundamental questions
in the gastric cancer field, defining the cells of and defining the distinct mediators of progression,
should be addressed together given their interconnectedness. We will evaluate the interplay of
genetic and environmental precipitants to gastric cancer using novel engineered mouse models
where we can selectively target key tumor suppressors in the gastric epithelium in concert with
relevant exposures. We will then deeply interrogate tissues with the combination of multi-omic
single cell technologies enabling dual analysis of gene expression and chromatin accessibility in
individual cells and the subsequent use of spatial transcriptomic tools allowing us to map features
of individual cell types spatially to refine the cellular origins of these altered cell types. In concert
to defining cellular origins of the two primary classes of gastric cancer, our integrated multi-omic
and spatial analyses will be evaluated to define changes in cellular programs and candidate
mediators of these altered phenotypes. Furthermore, we can define the interaction of
environmental exposures in gastric tumorigenesis. Subsequently, we will perform functional
validation of candidate mediators of progression, evaluating both features intrinsic to gastric
epithelial cells and those emerging from the microenvironment. These studies will both address
longstanding debates over origins of these cancers and define new targets to prevent cancer
development.

## Key facts

- **NIH application ID:** 11063514
- **Project number:** 3R01CA272891-02S1
- **Recipient organization:** COLUMBIA UNIVERSITY HEALTH SCIENCES
- **Principal Investigator:** Silas Maniatis
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $15,925
- **Award type:** 3
- **Project period:** 2023-09-01 → 2027-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11063514

## Citation

> US National Institutes of Health, RePORTER application 11063514, Elucidating the mechanisms by which the extracellular matrix contribute to gastroesophageal cancer pathobiology (3R01CA272891-02S1). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/11063514. Licensed CC0.

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