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El-Rifai Lab

Molecular mechanisms of gastroesophageal tumorigenesis

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Investigator / Contact Person Wael El-Rifai

Research

Dr. El-Rifai leads a competitively NCI-funded research program in upper GI cancers. Dr. El-Rifai has made significant contributions in the area of gastric cancer, Barrett's esophagus and esophageal adenocarcinoma. His major research interests are in genetics, epigenetics, and cancer biology, focusing on gastrointestinal tumorigenesis and the development of novel strategies for cancer therapeutics. His laboratory provides unique training experiences in diverse areas of cancer research that include molecular mechanisms of tumorigenesis and drug resistance. Dr. El-Rifai's research encompasses animal models as tools for identification of tumor development and progression. In the field of gastric cancer, his work using the trefoil factor 1 knockout mouse model in conjunction with in vitro assays and human tissues samples has shown that TFF1 has potent anti-inflammatory and tumor suppressor functions, which protect against H. pylori-mediated development of gastric cancer in mouse and human.

He has a long-standing interest in understanding the modulation of molecular pathways through genetic and epigenetic events. Dr. El-Rifai lab has made significant contributions to our understanding of the molecular mechanisms underlying the development and progression in Barrett's carcinogenesis. Barrett's esophagus, the main risk factor for esophageal adenocarcinoma, develops as a consequence of chronic gastroesophageal reflux disease where the distal esophagus becomes abnormally exposed to acid and bile refluxate from the stomach. The pioneering work from his lab has shown that DNA methylation wipes out the expression of several protective antioxidant enzymes, important for protecting against reflux-induced oxidative stress and DNA damage, thereby facilitating progression of metaplastic Barrett's esophagus to esophageal cancer. The El-Rifai's laboratory identified a number of genomic hot spots and has systematically characterized the 1q, 17q, and 20q amplicons by integrating genomic and gene expression data. His work has led to the identification of DARPP-32 and Aurora kinase A as critical targets in gastric and esophageal tumorigenesis, which regulate chemotherapeutic response. His published studies have given new insights to understanding the molecular mechanisms of resistance to ERBB2 and EGFR inhibitors.  His pioneering work in understanding the role of Aurora kinase A (AURKA) in carcinogenesis has led to several ongoing clinical trials targeting AURKA in cancer. Dr. El-Rifai serves as a co-investigator on a clinical trial testing AURKA inhibitor (ClinicalTrials.gov Identifier: NCT02319018) for treating gastrointestinal cancers, now open in Vanderbilt, Yale, and Hopkins. Dr. El-Rifai has several international collaborations in Africa, Europe, and South America. He has published more than 150 research articles in highly cited peer-reviewed journals such as Journal of Clinical Oncology, Proceedings of National Academy of Science, Cancer Research, Oncogene, and Gastroenterology.


Complete List of Published Work:


http://www.ncbi.nlm.nih.gov/sites/myncbi/wael.el-rifai.1/bibliography/40773073/public/?sort=date&direction=ascending