# Project 3: Molecular Risk Stratification of Gastric Precancerous Lesions

> **NIH NIH P01** · STANFORD UNIVERSITY · 2024 · $357,876

## Abstract

ABSTRACT – PROJECT 3
Project 3 proposes a concerted effort to decrease the 10-15% rate of Helicobacter pylori (Hp) recrudescence
that is currently experienced by patients. Previous work by the investigators in this Program Project Grant has
shown that a small number of Hp colonies persist deep within the gastric glands after eradication therapy. These
colonies may not be detected using conventional clinical tests, as the colonies reside in recrudescence niches
that are consequently resistant to antibiotic treatment. Highly sensitive molecular technology can reveal the
presence of Hp in conventionally ‘negative’ gastric histology samples. The central hypothesis of Project 3 is that
use of highly sensitive, sequencing-based technology to identify persistent Hp organisms and guide eradication
may both prevent Hp recrudescence and arrest neoplastic progression. The specific aims of Project 3 are:
 (1) Leverage gene expression profiles of gastric epithelial cells as a predictor of gastric intestinal
 metaplasia (GIM) progression in Hp negative individuals.
 (2) Develop molecular risk-stratification strategies in Hp histology negative subjects.
In Aim 1, 300 Hp negative subjects will undergo RNA sequencing, and concordance with the ‘high-risk’ patterns
will be assessed through a gene expression vector. We will then translate the ‘high-risk’ expression signature
into a clinically useful multiplex IHC test. In Aim 2, samples from patients with GIM who are histology negative
for Hp on biopsies will be sequenced for molecular detection of Hp. A subset of patients will participate in a
randomized, placebo-controlled trial evaluating the effect of antibiotic therapy on molecular Hp titers. This trial
will demonstrate whether a sequencing-based eradication strategy can reduce Hp burden to molecularly
undetectable levels in human subjects.

## Key facts

- **NIH application ID:** 10932178
- **Project number:** 5P01CA265772-02
- **Recipient organization:** STANFORD UNIVERSITY
- **Principal Investigator:** JOO HA HWANG
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $357,876
- **Award type:** 5
- **Project period:** 2023-09-20 → 2028-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10932178

## Citation

> US National Institutes of Health, RePORTER application 10932178, Project 3: Molecular Risk Stratification of Gastric Precancerous Lesions (5P01CA265772-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10932178. Licensed CC0.

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