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My lab has multiple research interests in oro-esophageal cancer. We were interested in targeting oxidative stress and aberrant arachidonic acid metabolism for chemoprevention of oral squamous cell carcinoma and esophageal adenocarcinoma. Later we were interested in the molecular mechanisms of Barrett’s esophagus (BE) and gastroesophageal reflux disease (GERD). Over time, we have shifted our focus on cancer cell signaling and metabolism in esophageal squamous cell carcinoma (ESCC) with a translational intention.

1. Molecular mechanisms and targeted therapy of Nrf2high-ESCC: The goal is to understand how Nrf2 hyperactivation (due to DNA mutations) contribute to ESCC and to develop inhibitors of Nrf2 or its downstream kinases for targeted therapy of Nrf2high-ESCC. Our long-term goal is to translate some of these inhibitors into clinical trials. We believe Nrf2 inhibitors will be potentially used in combination with chemoradiotherapy and immunotherapy.

2. Molecular mechanisms and chemoprevention of alcohol-associated ESCC: We focus on the roles of Notch-Pax9 signaling and Nrf2-Acss2 axis-mediated metabolism in alcohol-associated carcinogenesis. Our long-term goal is to develop “benign cell boosters” (Nrf2 activators, Notch activators) as chemopreventive agents based on the concept of cancer evolution.