# H. pylori-induced Inflammation and Gastric Cancer

> **NIH NIH P01** · VANDERBILT UNIVERSITY MEDICAL CENTER · 2024 · $1,723,815

## Abstract

PROGRAM PROJECT GRANT OVERALL SUMMARY
Helicobacter pylori is the strongest risk factor for gastric adenocarcinoma, the fourth leading cause of cancer-
related death. One H. pylori determinant that increases gastric cancer risk is the cag type IV secretion system
(T4SS) which exports a bacterial oncoprotein, CagA, into host cells. Our entire group has collaboratively shown
that cag+ strains selectively activate a gastric stem cell population marked by Lrig1, as well as the EGF receptor,
ornithine decarboxylase, and spermine oxidase, host effectors that influence carcinogenesis. Project 2, Core A,
and Core B have additionally made the discovery that a pathway contributing to gastric carcinogenesis involves
reactive electrophiles and developed a novel intervention strategy using a clinically available electrophile
scavenger. Projects 1 and 3 demonstrated with Cores A and B that environmental components of the
exposome associated with gastric cancer, such as iron deficiency or a high salt diet, positively select for H. pylori
variants linked to increased cancer risk and augment the ability of cag+ strains to induce disease. Finally, all
Projects used unbiased approaches (Core B) to identify novel host effectors that increase cancer risk, including
bile acids. Our overarching Hypothesis is that differences in infecting strains, host responses, and environmental
exposures such as diet affect the risk of developing gastric cancer as a consequence of H. pylori infection. To
address this, our PPG integrates studies of host-pathogen interactions and oncogenic signaling initiated by
biomedical researchers who have made a strong commitment to research within the fields of carcinogenesis,
immunobiology, gastroenterology, and microbiology, and will generate results that would not be attainable
through independent investigation. The Projects below are driven by discrete hypotheses, yet are cohesive in
their focus on H. pylori-host interactions that induce cellular responses with carcinogenic potential.
Project 1. Effect of iron deprivation on H. pylori-induced gastric carcinogenesis (PI-Richard Peek)
Project 2. Polyamines and electrophiles in gastric cancer (PI-Keith Wilson)
Project 3. Regulation of H. pylori virulence by dietary factors that impact gastric cancer (PI-Tim Cover)
The efforts of each Project will be further unified by dynamic interactions with specific Core facilities, consisting
of Gastric Histopathology Core A, Proteomics and Metabolomics Core B, and Administrative Core C, which
includes sophisticated bioinformatics and statistics. By maintaining a grounded focus on interactions that occur
at the H. pylori-host interface, results from this proposed work will not only improve our understanding of gastric
cancer, but will also identify targets for prevention and more effective treatment of this devastating disease.

## Key facts

- **NIH application ID:** 10767083
- **Project number:** 2P01CA116087-17
- **Recipient organization:** VANDERBILT UNIVERSITY MEDICAL CENTER
- **Principal Investigator:** RICHARD M. PEEK
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $1,723,815
- **Award type:** 2
- **Project period:** 2009-01-01 → 2029-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10767083

## Citation

> US National Institutes of Health, RePORTER application 10767083, H. pylori-induced Inflammation and Gastric Cancer (2P01CA116087-17). Retrieved via AI Analytics 2026-05-31 from https://api.ai-analytics.org/grant/nih/10767083. Licensed CC0.

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