This R21 proposal is designed to use cell and mouse models to understand the role of NOTCH-PAX9 signaling pathway in alcohol-induced esophageal injury. We hypothesize that ethanol suppresses esophageal squamous cell differentiation through inhibition of the NOTCH-PAX9 signaling. We plan to test our hypothesis with two specific aims: (1) To determine whether ethanol suppresses esophageal squamous epithelial cell differentiation through inhibition of the NOTCH-PAX9 signaling. (2) To investigate whether NOTCH activation counteracts alcohol-induced esophageal injury. These studies are aimed to elucidate the role of NOTCH-PAX9 signaling in alcohol-induced esophageal injury. If proved true, it will lay down a solid mechanistic foundation to further study NOTCH activation as a novel mechanism-based preventive measure against alcohol-induced esophageal injury.
Alcohol drinking is a risk factor for esophageal diseases, however, the molecular mechanisms that alcohol drinking causes esophageal injury remains unclear. In this proposal, we hypothesize that ethanol suppresses esophageal squamous cell differentiation through inhibition of NOTCH-PAX9 signaling. If proved true, this study will lay down a solid mechanistic foundation to further study NOTCH activation as a novel mechanism- based preventive measure against alcohol-induced esophageal injury.
