# Establishing roles for the type I interferon/double-stranded RNA response and Helicobacter pylori-specific transcripts in the progression to metaplasia in gastric epithelium

> **NIH NIH K08** · WASHINGTON UNIVERSITY · 2020 · $158,058

## Abstract

Project Summary/Abstract
This application proposes a five year research career development program that focuses on the host and
microbial factors that contribute to gastric metaplasia. The comprehensive approach of exploring the host and
bacterial determinants of the metaplastic milieu will enhance our overall understanding of the dynamic interplay
that establishes a gastric pre-neoplastic state. The candidate is currently an Instructor in Medicine in the
Division of Gastroenterology at the Washington University School of Medicine. This proposal is an extension of
the candidate’s previous work demonstrating the ability of Helicobacter pylori to exploit metaplastic changes in
the host to expand its niche. The proposed experiments will incorporate gastric epithelial biology expertise from
the candidate’s mentor, Dr. Jason Mills, as well as Helicobacter pylori mutagenesis experience from the
candidate’s co-mentor, Dr. Rick Peek. Together, the candidate will be uniquely positioned to acquire new skill
sets and expand on previously developed techniques that will allow him to carve out a unique niche within the
field and transition to an independent physician scientist.
Gastric cancer remains one of the leading causes of cancer-related deaths worldwide. Chronic infection with
the stomach-adapted bacterium, Helicobacter pylori, represents the most significant risk factor for the
progression to gastric cancer. In the setting of chronic inflammation, loss of acid-secreting parietal cells from
the gastric corpus stimulates a reorganization of the corpus gland, characterized by an increased proliferation
of gastric progenitor cells and a reprogramming of post-mitotic chief cells at the gland base into a population of
proliferative metaplastic cells, a process that we have termed paligenosis. We recently demonstrated that
Helicobacter pylori exploits these metaplastic glandular changes to expand its colonization of the gastric
corpus, which is known to confer added oncogenic risk. This proposal describes a dual approach toward
identifying and characterizing the host and microbial factors that contribute to the establishment of the
metaplastic milieu. From the host perspective, a microarray analysis identified multiple components of the type
I IFN/dsRNA signaling pathway that were upregulated in two distinct models of gastric metaplasia. We will
dissect the role of this highly conserved antiviral pathway in the previously uncharacterized context of gastric
metaplasia. Similarly, we aim to demonstrate that the accumulation of endogenous dsRNA during paligenosis
serves as an intra-cellular signal for the development of gastric metaplasia. From the microbial perspective, a
newly developed bacterial RNAseq analysis found Helicobacter pylori-specific transcripts that were
differentially expressed in the gastric corpus. Using an established pipeline of in vivo and ex vivo experiments,
we will validate and characterize these genes in the context of Helicobacter pylo...

## Key facts

- **NIH application ID:** 9978060
- **Project number:** 5K08DK122116-02
- **Recipient organization:** WASHINGTON UNIVERSITY
- **Principal Investigator:** Jose Bernardo Saenz
- **Activity code:** K08 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $158,058
- **Award type:** 5
- **Project period:** 2019-09-01 → 2024-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9978060

## Citation

> US National Institutes of Health, RePORTER application 9978060, Establishing roles for the type I interferon/double-stranded RNA response and Helicobacter pylori-specific transcripts in the progression to metaplasia in gastric epithelium (5K08DK122116-02). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/9978060. Licensed CC0.

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