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Program on the Origins of Gastroesophageal Cancers

Key features of gastroesophageal carcinoma subtypes. The colored bands represent the proportion of the subtypes present within each anatomic region.

Credit: TCGA Research Network

This NCI program (funded through RFA-CA-21-026/RFA-CA-21-027) is designed to examine and define the earliest biological changes in malignant transformation. It builds on recent molecular classifications of gastroesophageal cancers, understanding of their cancer genomics, and advances in stem cell research to decipher how these cancers initially evolve at the cellular level. 

The initiative addresses the complex mechanisms and effectors that direct the growth of tumor-initiating and tumor-progenitor cells to originate gastroesophageal cancers. Additionally, the focus of the research projects is on gastric and gastroesophageal junction (GEJ) adenocarcinomas. 

An important goal of the program is to assess the biological mechanisms underlying increased prevalence of gastric and GEJ cancers in certain ethnic, racial, and gender populations. The initiative aims to tackle the evolution of deadly gastroesophageal cancers, generate a scientific platform that sustains this research field, and foster new and ongoing research collaborations in this area.

Program News

New grants for the Program on the Origins of Gastroesophageal Cancers were awarded in Fall 2022.

Dr. Julian Abrams, Dr. Michael Quante, and Dr. Harris Wang are examining the effects of circulating secondary bile acids produced by bacteria in the gut in gastroesophageal cancer development.

Using novel mouse models, organotypic cultures, single cell profiling, and spatial transcriptional analyses, Dr. Adam Bass, Dr. Silas Maniatis, and Dr. Karol Nowicki-Osuch are investigating how precursors to distinct classes of gastric cancer emerge in the stomach in response to underlying risk factors.

Dr. Eunyoung Choi and Dr. James Goldenring are studying mechanisms that control cell plasticity in the stomach leading to gastric carcinogenesis.

Using preclinical models, Dr. Frank McKeon, Dr. Jaffer Ajani, and Dr. Wa Xian are investigating the common stem cell of origin for GEJ cancer and gastric adenocarcinoma.

Dr. Anil Rustgi, Dr. Marcia Cruz-Correa, and Dr. James Wells are developing and characterizing model systems to to determine how precursors to gastric cancer form at different regions of the stomach and the mechanisms underlying ethnic disparities. 

Using single-cell sequencing, mouse models, and organoid systems, Dr. Timothy Wang and Dr. Jianwen Que are examining the role of gastroesophageal junction stem cells in the origin of Barrett’s Esophagus and gastroesophageal cancer.

The Coordinating Center for the Program on the Origins of Gastroesophageal Cancers, led by Dr. Chin Hur, Dr. Jeanine Genkinger, Dr. Jianhua Hu, and Dr. Nicholas Tatonetti, is providing coordination, infrastructure, and oversight to support the consortium in achieving the goals of the program, contributing to collaborative and outreach activities, as well as enabling the resolution of technical research challenges and technology development.

Contact for the Program

For additional information about the Program on the Origins of Gastroesophageal Cancers, please contact Dr. Rihab Yassin.

Funded Projects

Research Projects on the Origins of Gastroesophageal Cancers (R01s)

Institution Principal Investigator(s) Project Title
Columbia University Health Sciences Julian Abrams, Michael Quante, Harris Wang The Role of Secondary Bile Acids in Gastro-Esophageal Neoplasia
Columbia University Health Sciences Adam J. Bass, Silas Maniatis, and Karol P. Nowicki-Osuch Initiation of Diffuse and Intestinal Non-Cardia Gastric Cancer
Columbia University Health Sciences Anil K. Rustgi, Marcia R. Cruz-Correa, James M. Wells Mechanisms Underlying Gastric Intestinal Metaplasia and Carcinogenesis
Columbia University Health Sciences Timothy C. Wang, Jianwen Que Gastroesophageal Junction Stem Cells as the Origin of Barretts Esophagus and Cancer
University of Houston Frank D. McKeon, Jaffer A. Ajani, Wa Xian Common Stem Cell of Origin for Junctional and Gastric Adenocarcinoma
Vanderbilt University Eunyoung Choi, James R. Goldenring Cell Plasticity in the Origin of Gastric Carcinogenesis

Coordinating Center for the Program on the Origins of Gastroesophageal Cancers (U24)

Institution Principal Investigator(s) Project Title
Columbia University Health Sciences Chin Hur, Jeanine M. Genkinger, Jianhua Hu, Nicholas P. Tatonetti Coordinating Center for the Program on the Origins of Gastroesophageal Cancers
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