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El-Rifai Lab

Molecular mechanisms of gastroesophageal tumorigenesis

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Investigator / Contact Person Wael El-Rifai, M.D., Ph.D.


Dr. Wael El-Rifai is a Professor in the Department of Surgery at the University of Miami Leonard M. Miller School of Medicine, as well as the Associate Director of Basic Science and Co-Leader of the Tumor Biology Program. Dr. El-Rifai holds the John and Judy Schulte Senior Endowed Chair in Cancer Research. Dr. El-Rifai has authored more than 200 peer-reviewed articles that share his groundbreaking research on upper gastrointestinal carcinomas. He is an elected fellow of the American Association for Advances in Science. Dr. El-Rifai is the principal investigator on several National Cancer Institute grants, including a Research Program Project to study esophageal cancers. 

Dr. El-Rifai’s laboratory provides unique training experiences in diverse areas of cancer research, including molecular mechanisms of tumorigenesis, drug resistance, and targeted therapy. His research focuses especially on upper gastrointestinal carcinomas, examining the roles of infection, inflammation, and oxidative stress in tumorigenesis to develop more effective cancer treatments.

The El-Rifai lab is currently pursuing the following projects

The role of H. pylori infection in gastric tumorigenesis

Gastric cancer is the third leading cause of cancer-associated death with an estimated 1,033,701 new gastric cancer cases and 782,685 deaths in 2018. The overall 5-year survival rate of patients with gastric cancer is approximately 20%. However, the majority of gastric cancer patients are diagnosed at a late stage (Stage III or IV) in the United States, with a poor five-year survival rate of 5.2%. The World Health Organization has classified H. pylori as a class I carcinogen and the main risk factor for gastric cancer. Infection with H. pylori affects approximately 4.4 billion people around the globe. Cellular stress in response to infection or chemotherapy generates high levels of reactive oxygen species (ROS) and oxidative stress. Uncontrolled accumulation of ROS and high levels of oxidative stress are lethal cellular events. Therefore, gastric cells must develop protective antioxidant mechanisms to maintain oxidative stress below lethal levels. El-Rifai lab investigate the cross-talk between infection, inflammatory, oncogenic stress signaling and antioxidant response mechanisms. His lab also works to identify the druggable molecular vulnerabilities in treatment-resistant cancer cells. These studies are actively investigating the roles of FGFRs, AURKA and CDK1 in promoting stemness and EMT phenotypes in treatment resistance cancer cells.

Identify redox-dependent transcription networks in esophageal adenocarcinomas

The incidence of esophageal adenocarcinoma (EAC) has increased more than six-fold over the past three decades and continues to be on the rise in the Western world. EAC patients' 5-year survival rate being less than 15% underscores the need to understand the underlying biology to identify new therapeutic approaches.

Chronic gastroesophageal reflux disease (GERD), where acidic bile salts (ABS) abnormally refluxate into the esophagus, is the main risk factor for the development of metaplastic Barrett’s esophagus (BE) and

progression to EAC. Alterations in the redox status of reactive cysteine residues, located within the DNA-binding domain of redox-sensitive transcription factors (TFs), can suppress TFs’ DNA binding affinity and transcription activity. Therefore, the cellular redox capacity is paramount in promoting activity of oncogenic transcription factors, protecting tumorigenic cells and promoting their survival and expansion. In response to therapy, cancer cells undergo reprogramming of molecular networks to drive adaption and resistance to therapy. This reprogramming leads to the development of acquired adaptive survival properties with expansion of treatment-resistant cells (TRCs). The existence of TRCs is a major cause of both inherent (intrinsic) and acquired resistance, promoting therapeutic failure and tumor recurrence. TRCs develop an acquired adaptive phenotype, enriched for survival and expansion properties under genotoxic stimuli. Along these lines, several recent findings from mouse and human, suggest that APE1 and NRF2 activation play central role in shaping cell fate by promoting survival and expansion of cancer cells. El-Rifai lab investigates how the unique reflux-mediated oxidative environment during EAC tumorigenesis leads to the development of an adaptive increase in redox-dependent transcription network and stemness properties to mediate survival and expansion of cancer cells. This inherent adaptive mechanism is also crucial for cancer cell survival and resistance to chemotherapeutics. The lab also investigates novel approaches to target these redox-dependent activities to overcome therapeutic resistance in EAC.