# Project 3: Regulation of H. pylori Virulence by Dietary Factors That Impact Gastric Cancer

> **NIH NIH P01** · VANDERBILT UNIVERSITY MEDICAL CENTER · 2022 · $258,606

## Abstract

Project 3 Summary
Persistent colonization of the human stomach with the Gram-negative bacterium Helicobacter pylori is
associated with a marked increase in risk for the development of gastric adenocarcinoma. Gastric cancer is the
third leading cause of cancer-related death worldwide, and H. pylori has been classified as a type I carcinogen
by the World Health Organization. Among H. pylori-infected persons, the risk of gastric cancer is determined by
multiple variables, including H. pylori strain-specific virulence constituents, host genetic characteristics, and
environmental factors. The long-term goal of this work is to define the mechanisms by which H. pylori
infection can lead to gastric cancer and to develop improved approaches for identifying individuals who have
an increased risk for gastric cancer so they can be targeted for therapeutic intervention. In previous studies
with Project 1, we have shown that a high-salt diet increases the risk of gastric cancer in H. pylori-infected
gerbils. We now propose to define the mechanisms by which a high salt diet enhances H. pylori virulence and
increases gastric cancer risk. Aim 1 will define mechanisms by which a high salt diet modulates the gastric
mucosal inflammatory response, using both Mongolian gerbil and mouse models. Aim 2 will detect gastric and
blood alterations that are markers of gastric premalignant conditions, using imaging mass spectrometry and
metabolomics techniques. Aim 3 will define effects of a high salt diet on selection of H. pylori strains with
enhanced carcinogenic potential.!These aims will interdigitate with work proposed in Projects 1 and 2 and will
utilize both the Gastric Histopathology and the Proteomics and Metabolomics Cores. These studies will
lead to important advances in our understanding of the molecular mechanisms by which H. pylori infection and
a high salt diet promote the development of gastric cancer. Ultimately, these studies should lead to advances
in the prevention and therapy of malignancies that develop in the setting of chronic inflammation.
!

## Key facts

- **NIH application ID:** 10352429
- **Project number:** 5P01CA116087-15
- **Recipient organization:** VANDERBILT UNIVERSITY MEDICAL CENTER
- **Principal Investigator:** TIMOTHY L COVER
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $258,606
- **Award type:** 5
- **Project period:** 2008-12-01 → 2024-02-29

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10352429

## Citation

> US National Institutes of Health, RePORTER application 10352429, Project 3: Regulation of H. pylori Virulence by Dietary Factors That Impact Gastric Cancer (5P01CA116087-15). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10352429. Licensed CC0.

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