PROJECT SUMMARY/ABSTRACT Complications of gastro-esophageal reflux disease (GERD) such as intestinal metaplasia (Barrett’s esophagus) and esophageal adenocarcinoma continue to increase despite advances in medical and surgical therapies. This deficit in management is due in part to the incomplete understanding of the cellular and molecular mechanisms that mediate inflammation and epithelial restitution in GERD rather than progression to metaplasia. The focus of the project will be on the human esophageal myofibroblast (HEMF), a stromal cell with a recognized role in regulation of epithelial inflammation and proliferation via paracrine mediators. HEMFs adapted into three dimensional co-culture models that recapitulate human esophageal stratified squamous epithelium will be used to investigate HEMF-epithelial interactions in GERD. This project is particularly significant because it delineates the poorly understood role of stroma in GERD related esophageal injury and is the basis for the development of novel therapeutics for this chronic disorder.