# The role of type 2 inflammation in the initiation and progression of metaplastic differentiation and neoplastic transformation of gastric epithelia

> **NIH NIH R01** · UNIVERSITY OF MIAMI SCHOOL OF MEDICINE · 2022 · $63,971

## Abstract

This application requests the NCI diversity research supplement funding to active an NCI grant in response
to PA-21-071, to support the research training and career development of a graduate student from an
underprivileged racial/ethnic and social/economic background. In this diversity supplement proposal, a
predoctoral graduate student will lead a specific project that is immediately relevant and critically complementary
to and yet clearly distinct from the parent NCI grant. The diversity supplement proposal is tailored for the graduate
student’s interest to understand host-pathogen interaction in gastric tumorigenesis prompted by genetic
predisposition of autoimmunity. There is evidence that type 2 inflammation, characterized by the pathway
initiated by type 2 cytokine IL4 and IL13, plays a critical role in gastric tumorigenesis initiated by either
autoimmunity or H. pylori. The objective in this diversity supplement proposal is to investigate potential synergy
of H pylori and autoimmune type 2 inflammation in the initiation and progression of gastric tumorigenesis. In the
CTLA4KD model, tumorigenesis is initiated by autoimmunity caused by CTLA4 insufficiency, which mimics the
effect of CTLA4 polymorphisms or heterozygous mutations in humans. It is driven by host-intrinsic factor as
germ-free conditions did not affect the autoimmunity development and initiation of tumorigenesis. Therefore, the
CTLA4 model presents a unique tool to study potential synergy of H pylori and host-intrinsic immune
dysregulation, in autoimmune gastritis and its progression to pre-malignancy and cancer. Specifically, the
graduate student, while undergoes research training and career development mentoring, will learn to use
rigorous scientific reasoning and cutting-edge technology to address the follow two questions: 1) How does H.
pylori infection affect gastric autoimmunity and onset of pre-malignancy caused by host-intrinsic dysregulation
due to CTLA4 insufficiency? 2) How does H. pylori interact with pre-malignant cells and affect their lineage
progression? The student will take a well-crafted curriculum designed for PhD training as well as participate in
well-orchestrated career skill activities. The student will work with a mentor team to develop an individual career
development plan (IDP) and individualized mentoring plan (IMP), to guide the student through the training
process to become independent and creative scholar excelling in conducting interdisciplinary research in
microbiology, immunology and cancer biology. Through the research and career training, the student is expected
to be not only well-equipped to advance their own scientific careers but also well-prepared to face emerging
challenges in the world with creative solutions, with well-rounded scientific professionalism to serve the society.

## Key facts

- **NIH application ID:** 10598700
- **Project number:** 3R01CA245673-03S1
- **Recipient organization:** UNIVERSITY OF MIAMI SCHOOL OF MEDICINE
- **Principal Investigator:** Zhibin Chen
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $63,971
- **Award type:** 3
- **Project period:** 2020-06-01 → 2025-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10598700

## Citation

> US National Institutes of Health, RePORTER application 10598700, The role of type 2 inflammation in the initiation and progression of metaplastic differentiation and neoplastic transformation of gastric epithelia (3R01CA245673-03S1). Retrieved via AI Analytics 2026-06-27 from https://api.ai-analytics.org/grant/nih/10598700. Licensed CC0.

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