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This Program Project grant entitled “Mechanisms of Esophageal Carcinogenesis” seeks to define and elucidate the molecular mechanisms underlying esophageal carcinogenesis with translation to new strategies in therapy. Based upon historical interactive collaborations between the Project Leaders and usage of the Scientific Core Facilities, this program project focuses upon hypothesis-driven research that is innovative. The experience and expertise of the Project Leaders, in concert with the platforms provided by the Core Facilities, will result in enhancement of the research that would not be possible if the projects were independent of each other.

Research Projects

Transformed Esophageal Epithelial Cells and Tumor Microenvironment

This project focuses upon the biological roles of the cooperation between p120-catenin and p53 tumor suppressor genes in the formation of esophageal tumor cells as well as the interplay of these tumor cells with CAFs and MDSCs in the esophageal tumor microenvironment.

Protein Ubiquitylation in Esophageal Cancer

This project elucidates the manner in which cyclin D1 is regulated and defines the novel role of the Fbx4 mutations in esophageal carcinogenesis, with translation into the development of therapeutic approaches. Specifically, SCFFBX4-aB crystallin E3 ligase maintains threshold levels of the cyclin D1/CDK4 kinase critical for esophageal cell growth and homeostasis. Therapeutic strategies targeting the cyclin D1/CDK4 kinase, or key downstream effectors (such as PRMT5) may provide significant therapeutic benefit in the treatment of esophageal cancer.

Genome-Guided Therapeutic Vulnerabilities in Esophageal Cancer

This project has discovered genomic amplifications of genes encoding ERBB-family kinases and cell cycle mediators in esophageal cancers (both ESCC and EAC) will serve as biomarkers to guide use of targeted inhibitors and that testing of therapeutics in genomically defined model systems will allow the identification of optimal agents and rational combinations of targeted agents.

Core Facilities

Three highly successful Core facilities are designed to provide esophageal cancer-specific services for the stimulation of collaborative research:

The Program Project will continue to foster interdisciplinary research at Penn, DFCI, MUSC and nationally that leads to a cooperative understanding of the molecular processes that form and regulate esophageal carcinogenesis with innovative opportunities in translational medicine. This highly productive and synergistic P01 involves integrated and innovative Projects, which are supported by robust and unique Core Facilities. Institutional support is truly outstanding. We seek to provide unique benefits in esophageal cancer to the biomedical research and clinical communities as well as to our patients.

Program Leadership

Anil K. Rustgi, MD
Program Director
T. Grier Miller Professor of Medicine and Genetics
Chief, Division of Gastroenterology
Co-Director, Tumor Biology Program, Abramson Cancer Center

Tannaz Fakheri
Program Project Administration
Grants Manager, Division of Gastroenterology

External Advisory Board

Alex Almasan, PhD
Professor of Cancer Biology and Molecular Medicine
Department of Cancer Biology, Lerner Research Institute
Cleveland Clinic Lerner College of Medicine of Case Western Reserve University

Ethan Dmitrovsky, MD (Chair)
American Cancer Society Professor
Provost and Executive Vice-President
MD Anderson Cancer Center

Yelena Y. Janjigian, MD
Chief Attending Physician
Gastrointestinal Oncology Services
Memorial Sloan-Kettering Cancer Center

J. Jack Lee, PhD
Professor of Biostatistics
The University of Texas
MD Anderson Cancer Center

Christopher Willett, MD
Professor and Chairman
Department of Radiation Oncology
Duke University Medical Center

Internal Advisory Board

Carmen E. Guerra, MD, MSCE
Associate Professor of Medicine
Associate Director of Diversity and Outreach, Abramson Cancer Center
Vice Chair of Diversity and Inclusion, Department of Medicine

Gustavo W. Leone, PhD
Director, Hollings Cancer Center
Grace E. DeWolff Endowed Chair in Medical Oncology
Senior Associate Dean for Oncology in the College of Medicine
Professor of Biochemistry and Molecular Biology
Medical University of South Carolina

Erle S. Robertson, PhD
Vice Chair of Otorhinolaryngology
Professor of Microbiology
Director, Tumor Virology Program

Deborah Schrag, MD, MPH
Chief, Division of Population Sciences
Center for Gastrointestinal Oncology
Professor of Medicine
Harvard Medical School

Robert H. Vonderheide, MD, DPhil (Chair)
Director, Abramson Cancer Center
John H. Glick, MD Abramson Cancer Center's Director Professor


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