Esophageal cancer is common worldwide and comprises two subtypes: esophageal squamous cell cancer (ESCC) and esophageal adenocarcinoma (EAC). Unfortunately, most patients present at late stages, thereby making survival rates low at less than 5% at 5 years. This grim prognosis mandates the utilization of innovative and unique genetically engineered mouse models developed by our research team to implement new strategies for functional genomics, prevention, imaging and therapy. The unique consortium involves long-standing collaborations and publications between recognized experts in the field of esophageal cancer from the University of Pennsylvania, Columbia University, and Massachusetts General Hospital. In particular, the Principal Investigators are Dr. Anil Rustgi (University of Pennsylvania), Dr. Timothy Wang (Columbia University) already within the NCI Tumor Microenvironment Network, and Dr. Umar Mahmood (Massachusetts General Hospital). The overarching goals of this U01 grant proposal are the following: (1) To utilize innovative models of esophageal cancer as a platform for elucidating the link between inflammation and cancer in the tumor microenvironment;and (2) To provide new approaches in the imaging of esophageal cancer for advances in translational medicine. These goals will be pursued through five interrelated Specific Aims that are trans-disciplinary and trans-institutional, and provide new We hope that the unique interrelated models developed by Drs. Rustgi and Wang may provide a new, future direction in tissue imaging of precancerous and cancerous lesions facilitated by the development of mouse upper endoscopy, non-invasive imaging technologies and molecular probes (tracking inflammatory/immune cells in the esophageal cancer microenvironment) by Dr. Umar Mahmood, which would have a great impact upon early detection of esophageal cancer in the human. In aggregate, this highly accomplished research team is poised to translate models of esophageal cancer into the eradication of human esophageal cancer, which would alter clinical approaches in the United States and worldwide. The proposed research is in concert with the recommendations by the NCI progress group report on upper Gl cancers, and the NCI Think Tank recommendations on the Tumor Microenvironment as well as Inflammation and Cancer.

Public Health Relevance

Esophageal cancer comprises two main subtypes, esophageal squamous cell cancer (ESCC) and esophageal adenocarcinoma (EAC), both common in the US and worldwide. In fact, ESCC is the 5th most common cancer amongst males worldwide and afflicts African-Americans with a high predilection in the US. EAC has the fastest rate of increase of any cancer in the US. The proposed research will translate models into improving clinical outcomes of esophageal cancers.

National Institute of Health (NIH)
National Cancer Institute (NCI)
Research Project--Cooperative Agreements (U01)
Project #
Application #
Study Section
Special Emphasis Panel (ZCA1-SRLB-X (O1))
Program Officer
Mohla, Suresh
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
University of Pennsylvania
Internal Medicine/Medicine
Schools of Medicine
United States
Zip Code
Arvold, Nils D; Heidari, Pedram; Kunawudhi, Anchisa et al. (2016) Tumor Hypoxia Response After Targeted Therapy in EGFR-Mutant Non-Small Cell Lung Cancer: Proof of Concept for FMISO-PET. Technol Cancer Res Treat 15:234-42
Schellnegger, Raphael; Quante, Anne; Rospleszcz, Susanne et al. (2016) Goblet Cell Ratio in Combination with Differentiation and Stem Cell Markers in Barrett Esophagus Allow Distinction of Patients with and without Esophageal Adenocarcinoma. Cancer Prev Res (Phila) :
Heidari, Pedram; Esfahani, Shadi A; Turker, Nazife S et al. (2015) Imaging of Secreted Extracellular Periostin, an Important Marker of Invasion in the Tumor Microenvironment in Esophageal Cancer. J Nucl Med 56:1246-51
Karakasheva, Tatiana A; Waldron, Todd J; Eruslanov, Evgeniy et al. (2015) CD38-Expressing Myeloid-Derived Suppressor Cells Promote Tumor Growth in a Murine Model of Esophageal Cancer. Cancer Res 75:4074-85
Kagawa, S; Natsuizaka, M; Whelan, K A et al. (2015) Cellular senescence checkpoint function determines differential Notch1-dependent oncogenic and tumor-suppressor activities. Oncogene 34:2347-59
Long, Apple; Giroux, Véronique; Whelan, Kelly A et al. (2015) WNT10A promotes an invasive and self-renewing phenotype in esophageal squamous cell carcinoma. Carcinogenesis 36:598-606
Rhim, Andrew D; Rustgi, Anil K (2015) Three-dimensional organotypic culture of stratified epithelia. Cold Spring Harb Protoc 2015:349-53
Sheth, Rahul A; Arellano, Ronald S; Uppot, Raul N et al. (2015) Prospective trial with optical molecular imaging for percutaneous interventions in focal hepatic lesions. Radiology 274:917-26
Turker, N Selcan; Heidari, Pedram; Kucherlapati, Raju et al. (2014) An EGFR targeted PET imaging probe for the detection of colonic adenocarcinomas in the setting of colitis. Theranostics 4:893-903
Habibollahi, Peiman; Waldron, Todd; Heidari, Pedram et al. (2014) Fluorescent nanoparticle imaging allows noninvasive evaluation of immune cell modulation in esophageal dysplasia. Mol Imaging 13:1-11

Showing the most recent 10 out of 25 publications