Thursday, January 1, 2026 1/1/2026

Common Stem Cell of Origin for Junctional and Gastric Adenocarcinoma

Award Number: R01CA272906
ORGANIZATION: NATIONAL CANCER INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 09/15/2022
PERIOD OF PERFORMANCE END DATE: 08/31/2027

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Common Stem Cell of Origin for Junctional and Gastric Adenocarcinoma - SUMMARY Despite their emergence from distal esophagus and distal stomach, respectively, esophageal adenocarcinoma (EAC) and intestinal gastric cancer (iGC) share the natural histories and molecule genetics of a single disease. Historically, EAC and iGC were among the first cancers to be linked to the prior presence of discrete, pre- cancerous lesions that can progress to dysplasia and then invasive disease over a two-decade interval. In both cases the earliest precancerous lesion was an odd intestinal metaplasia; IM known as Barrett's esophagus (BE) for EAC and gastric intestinal metaplasia (GIM) for iGC. These common evolutionary features have been extended by cancer genetics breakthroughs that place EAC and iGC into single cluster distinct from other gastric and esophageal cancers. While it was widely anticipated that advances in endoscopic and ablative technologies applied to precursor lesions would spell the end of EAC and iGC, rates of EAC and iGC have not appreciably decreased and most patients still present with advanced disease and poor five-year survival. This dire clinical reality has predicated a broad effort to understand the cell-of-origin of these diseases, their earliest emergence towards pathology, as well as their detection and pharmaceutical elimination. A highly collaborative team consisting of upper gastrointestinal oncologists, stem cell and molecular biologists, experts in murine cancer modeling, and proteomics specialists has employed advanced stem cell cloning technologies to capture patient-matched stem cells in each of the successive lesions in patients with EAC and iGC. In addition to the high-resolution phylogenetics afforded by these stem cells, this analysis has revealed the BE and GIM stem cells are indistinguishable at the level of whole genome expression profiling down to the level of homeotic transcription factors that define cellular identity. Common cell surface markers of BE and GIM stem cells identify a discrete population of cells at both the gastroesophageal (GE) junction and in the distal stomach of normal mice which we hypothesize are the intrinsic source of the IM for EAC and iGC respectively. These markers have also enabled the cloning of the corresponding site-specific stem cells, which we find to be indistinguishable gene expression profiles and to be committed to IM upon in vitro differentiation. In three aims, we will 1) use similar methods to clone the intrinsic IM stem cells from human fetal and adult GE junctions and gastric mucosa; 2) engineer mouse models for conditional expression of oncogenic factors in intrinsic IM cells; and 3) identify small molecules that selectively target intrinsic IM stem cells as leads for therapeutics to prevent EAC and iGC. We anticipate that the studies proposed herein will provide new insights into the biology and origin of these remarkably similar and widespread cancers, provide datasets essential for prospective early detection screens, and yield highly selective therapeutics that eliminate the nascent lesions essential for the evolution of these cancers.


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	WAKE FOREST UNIVERSITY HEALTH SCIENCES	MEDICAL CENTER BLVD	WINSTON SALEM	NC	27157	FORSYTH	USA	Cancer Biology Research	000	4	12/4/2025	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$0
														Subtotal = $0

Issue Date FY: 2025 ( Subtotal = $949,184 )
2025	2025	WAKE FOREST UNIVERSITY HEALTH SCIENCES	MEDICAL CENTER BLVD	WINSTON SALEM	NC	27157	FORSYTH	USA	Cancer Biology Research	001	4	9/15/2025	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$949,184
2025	2024	UNIVERSITY OF HOUSTON SYSTEM	4300 MARTIN LUTHER KING BLVD	HOUSTON	TX	77204	HARRIS	USA	Cancer Biology Research	000	3	9/12/2025	NON-COMPETING CONTINUATION	$0
														Subtotal = $949,184

Issue Date FY: 2024 ( Subtotal = $888,662 )
2024	2024	UNIVERSITY OF HOUSTON SYSTEM	4300 MARTIN LUTHER KING BLVD	HOUSTON	TX	77204	HARRIS	USA	Cancer Biology Research	000	3	8/22/2024	NON-COMPETING CONTINUATION	$888,662
														Subtotal = $888,662

Issue Date FY: 2023 ( Subtotal = $916,726 )
2023	2023	UNIVERSITY OF HOUSTON SYSTEM	4300 MARTIN LUTHER KING BLVD	HOUSTON	TX	77204	HARRIS	USA	Cancer Biology Research	000	2	9/8/2023	NON-COMPETING CONTINUATION	$916,726
														Subtotal = $916,726

Issue Date FY: 2022 ( Subtotal = $949,184 )
2022	2022	UNIVERSITY OF HOUSTON SYSTEM	4800 W CALHOUN ST STE 316	HOUSTON	TX	77004	HARRIS	USA	Cancer Biology Research	000	1	9/15/2022	NEW	$949,184
														Subtotal = $949,184

Grand Total All Awards = $3,703,756

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Common Stem Cell of Origin for Junctional and Gastric Adenocarcinoma

Award Number: R01CA272906

ORGANIZATION: NATIONAL CANCER INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 09/15/2022

PERIOD OF PERFORMANCE END DATE: 08/31/2027

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