BLRD Research Career Scientist Award Application

Miami Va Health Care System, Miami FL

Investigators

Linked publications & trials

Abstract

Dr. El-Rifai is a Research Career Scientist funded by a VA merit award since 2012. He is a member of the Research and Development committee at the Miami VA who participates in active mentoring of junior scientists. He is also the vice chair and Professor of Surgery, Leader of the Tumor Biology Research Program, and Associate Director for Program Development at the University of Miami Miller School of Medicine and Sylvester Comprehensive Cancer Center. As the Associate Director for Program Development at Sylvester, he works with the senior leadership to create new research programs, including faculty alignment, recruitment and resource allocation. Dr. El-Rifai oversees the research development, mentors junior faculty, and participates in research training of residents and fellows. Dr. El-Rifai’s research is funded by VA merit awards since 2012 and continuous NCI funding for 20 years with 197 peer-reviewed publications, and over 220 scientific abstracts. His research aims for a better understanding of the biology of gastro-esophageal cancers and developing novel therapeutic approaches. His laboratory provides unique training experiences in genetics, epigenetics, and cancer biology, focusing on molecular mechanisms of gastrointestinal tumorigenesis and the development of novel strategies for cancer therapeutics. Dr. El-Rifai has trained more than 75 personnel that included undergraduate and graduate students, postdocs, and residents. He has mentored more than 15 junior faculty members, many of whom have progressed to independent faculty positions. Dr. El-Rifai’s laboratory works closely with basic science and clinical research colleagues for one common goal; a better clinical outcome. The El-Rifai laboratory utilizes innovative mouse models, 3D organoid cultures, and human tissue samples. Dr. El-Rifai has made significant contributions in the area of gastric cancer and esophageal adenocarcinoma. He has been successful in identifying the signaling links between inflammation and cancer in gastric and esophageal adenocarcinomas, discovering novel genes that mediate drug resistance, and developing targeted therapy approaches for upper GI cancers. Dr. El-Rifai 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 the development of gastric cancer in mouse and human. Dr. El-Rifai lab has made significant contributions to the current understanding of the molecular mechanisms underlying the development of esophageal adenocarcinoma (EAC). Barrett’s esophagus, the main risk factor for EAC, develops as a consequence of chronic gastroesophageal reflux disease. He demonstrated an epigenetic switch that turns off several anti-tumorigenic antioxidant response genes, concordant with activation of other genes that promote a pro-tumorigenic antioxidant response. 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 EAC. The pro-tumorigenic response included constitutive overexpression of redox factor 1 (REF1, also known as APE1) and transcription factor NFE2- related factor 2 (NRF2), promoting DNA damage repair, oncogenic signaling, and cancer cell survival Working with pharmaceutical companies, he tested novel targeted therapy strategies and established MLN8237, alisertib, as a potent anti-cancer drug. MLN8237 is now listed on the NCI Cooperative Research and Development Agreement (CRADA) and is studied in several clinical trials. Dr. El- Rifai, working with medical oncology colleagues, has moved several concepts such as targeting AURKA and mTOR into clinical trials. In summary, cancer is a disease with no boundaries; Dr. El-Rifai has a firm belief that clinical and translational research founded on strong basic science discoveries is the way to win our battle against cancer.