Friday, January 9, 2026 1/9/2026

Molecular Understanding and Targeting of Determinant Factors in Gastric Tumorigenesis

Award Number: R01CA236905
ORGANIZATION: NATIONAL CANCER INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 04/01/2021
PERIOD OF PERFORMANCE END DATE: 03/31/2027

Group Awards By:

View Award Description

Molecular Understanding and Targeting of Determinant Factors in Gastric Tumorigenesis - ABSTRACT Gastric cancer (GC) is the fifth most common malignancy and the third most lethal cancer worldwide, with a 5-year survival rate of 5-10% in advanced stages. The long-term goal of our research is to develop novel interventions to prevent and treat gastric cancer (GC) based on molecular targeting of crucial events in GC carcinogenesis. This application is based on an exciting finding that mice with villin-promoter– driven PPAR-d overexpression (villin-PPAR-d mice) spontaneously developed large and invasive GCs. Our published data showed that PPAR-d was upregulated in human GC tissues and this upregulation was associated with poor prognosis of patients. Villin promoter is active in a small subpopulation of gastric epithelial cells that are considered villin-positive gastric progenitor cells (V-GPCs). Cancer stem cells (CSCs) are thought to arise from transformation of normal stem/progenitor cells to drive tumor formation. We found that PPAR-d enhanced the stemness of V-GPCs and enabled V-GPCs to form tumors via activating the PPAR-d–interferon- gamma (IFNG) signaling loop. Furthermore, we also found 1) CCL20 is the most markedly upregulated chemokine by PPAR-d overexpression in V-GPCs, and 2) CCR6+CD45+ cells (CCR6 is the sole receptor of CCL20) have significantly higher IFNG mRNA expression than CCR6-CD45+ cells do. Helicobacter pylori (H. pylori) is a class I carcinogen for human GC. Chronic H. pylori infection, currently affecting nearly half of the world population, is a known strong risk factor for human GC. H. pylori infection increases PPAR-d, CCL20, and IFNG, which in turn promotes H. pylori–induced gastric inflammation, enhances GPCs’ stemness and promotes gastric epithelial proliferation in mice and humans. Whether this PPAR-d overactivation is required for H. pylori– induced GC is largely unknown. Addressing this knowledge gap is important to the public, especially for individuals who suffer from chronic H. pylori infection, because PPAR-d is a druggable protein for which both agonists and antagonists have been developed, and PPAR-d agonists are being used for noncancerous indications (e.g. enhancing muscle endurance). Thus, we hypothesize that PPAR-d overactivation in GPCs drives GC via upregulating the PPAR-d–CCL20/CCR6–IFNG signaling pathway and molecular targeting of this pathway could be a novel intervention modality for GC. Aim 1 will determine the role of PPAR-d upregulation in V-GPCs and Lgr5-positive GPCs (L-GPCs) at adult onset on GC carcinogenesis. Aim 2 will determine the effect of PPAR-d genetic deletion/loss of function in V-GPCs or L-GPCs on H. felis-induced GC tumorigenesis. H. felis is a close relative of H. pylori that has analogous effects in mice to those of H. pylori in humans. Aim 3 will determine the molecular mechanisms underlying dysregulated PPAR-d–IFNG signaling and evaluate the effects of molecular targeting of this pathway on GC carcinogenesis. We expect that completion of this proposal will not only provide new insights into the molecular pathogenesis of GC, but also advance the development of novel mechanism-based approaches for GC prevention and therapy.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2026 ( Subtotal = $0 )
2026	2025	THE UNIVERISTY OF TEXAS M.D. ANDERSON CANCER CENTER	1515 HOLCOMBE BLVD	HOUSTON	TX	77030	HARRIS	USA	Cancer Biology Research	000	5	1/7/2026	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2025 ( Subtotal = $370,575 )
2025	2025	THE UNIVERISTY OF TEXAS M.D. ANDERSON CANCER CENTER	1515 HOLCOMBE BLVD	HOUSTON	TX	77030	HARRIS	USA	Cancer Biology Research	000	5	3/3/2025	NON-COMPETING CONTINUATION	$333,518
2025	2025	THE UNIVERISTY OF TEXAS M.D. ANDERSON CANCER CENTER	1515 HOLCOMBE BLVD	HOUSTON	TX	77030	HARRIS	USA	Cancer Biology Research	001	5	5/23/2025	NON-COMPETING CONTINUATION	$37,057
														Subtotal = $370,575

Issue Date FY: 2024 ( Subtotal = $352,047 )
2024	2024	THE UNIVERISTY OF TEXAS MD ANDERSON CANCER CENTER, A COMPONENT OF THE UNIVERISTY OF TEXAS SYSTEM	1515 HOLCOMBE BLVD	HOUSTON	TX	77030	HARRIS	USA	Cancer Biology Research	000	4	3/7/2024	NON-COMPETING CONTINUATION	$333,518
2024	2024	THE UNIVERISTY OF TEXAS MD ANDERSON CANCER CENTER, A COMPONENT OF THE UNIVERISTY OF TEXAS SYSTEM	1515 HOLCOMBE BLVD	HOUSTON	TX	77030	HARRIS	USA	Cancer Biology Research	001	4	4/16/2024	NON-COMPETING CONTINUATION	$18,529
														Subtotal = $352,047

Issue Date FY: 2023 ( Subtotal = $363,164 )
2023	2023	UNIVERSITY OF TEXAS M. D. ANDERSON CANCER CENTER, THE	1515 HOLCOMBE BLVD	HOUSTON	TX	77030	HARRIS	USA	Cancer Biology Research	000	3	3/30/2023	NON-COMPETING CONTINUATION	$363,164
														Subtotal = $363,164

Issue Date FY: 2022 ( Subtotal = $363,164 )
2022	2022	UNIVERSITY OF TEXAS M. D. ANDERSON CANCER CENTER, THE	1515 HOLCOMBE BLVD	HOUSTON	TX	77030	HARRIS	USA	Cancer Biology Research	000	2	5/9/2022	NON-COMPETING CONTINUATION	$363,164
														Subtotal = $363,164

Issue Date FY: 2021 ( Subtotal = $370,575 )
2021	2021	UNIVERSITY OF TEXAS M D ANDERSON CANCER CENTER	1515 HOLCOMBE BLVD UNIT 207	HOUSTON	TX	77030	HARRIS	USA	Cancer Biology Research	000	1	3/25/2021	NEW	$370,575
														Subtotal = $370,575

Grand Total All Awards = $1,819,525

Top

All Categories

About

Search

Reports

Data Submission

Award Information

Molecular Understanding and Targeting of Determinant Factors in Gastric Tumorigenesis

Award Number: R01CA236905

ORGANIZATION: NATIONAL CANCER INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 04/01/2021

PERIOD OF PERFORMANCE END DATE: 03/31/2027

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer