Chen, Xiaoxin Luke

1. Molecular mechanism of intestinal metaplasia in the esophagus (Barrett's esophagus) and chemoprevention of esophageal adenocarcinoma: The goal of this project is to study the roles of gastroesophageal refluxate (acid and bile acids), genetic and epigenetic pathways in the development of Barrett's esophagus, the premalignant lesion of esophageal adenocarcinoma, in cell culture, animal models, and humans. Current studies focus on three areas: (1) How a group of squamous and intestinal transcription factors contribute to intestinal metaplasia in cell culture, surgical models (rats, mice, pigs) and genetically models (zebrafish, pigs). (2) How genetic factors and gene-environment interactions may contribute to racial disparity of Barrett's esophagus, e.g., why Caucasian Americans are more susceptible to Barrett's esophagus than African Amercians. (3) What molecular pathways may regulate resistance properties of esophageal squamous epithelium in the presence of gastroesophageal reflux.

2. Molecular mechanism and chemoprevention of alcohol and tobacco-associated oral cancer: We focus on aberrant arachidonic acid metabolism (especially the 5-lipoxygenase pathway) and oxidative damage in oral carcinogenesis of carcinogen-induced models in hamsters and mice. Both pharmacological (pharmaceutical and dietary agents) and genetic approaches are employed to elucidate the mechanism of oral carcinogenesis and design mechanism-based chemopreventive strategies. Potential candidate agents are further tested in human clinical trials.