Investigator: Yinsheng Wan, Providence College

Scientific Theme: Cancer

Abstract: Melanoma is a disease that is extremely aggressive and yet lack of cure. The cellular and molecular mechanism of the aggressiveness remains to be fully elucidated. Our previous studies have shown that melanoma cells exhibit constitutive mTOR activity that may be associated with aggressiveness. However, the cell signaling pathways leading to mTOR up-regulation is unclear. Published data have suggested that cell membrane channels may contribute to the mTOR activity in malignant tumor. However, the studies on electrophysiology of melanoma cells and their counterpart melanocytes are sporadic. Our preliminary studies have indicated that melanoma cells have aberrant Na current compared to normal melanocytes. In this proposed project, Na channels on melanocytes and melanoma cells and mTOR activity will be investigated using Patch Clamping technique, Western blot analysis and confocal microscopy. Inhibitors of mTOR will be used to study the Na current and Na channel blockers will be applied to study the mTOR activity in both cells. At the completion of this proposed project, our research will provide insights into the understanding of the molecular mechanism of aggressiveness of melanoma and reveal molecular targets for drug development. This project will be performed at Providence College during summer of 2015 and ensuing fall and spring semesters with three undergraduate students including Ryan Garrity, Jeanine Justiniano and Ben Gallant who are currently working in our laboratories.

Human Health Relevance: Melanoma is a disease that is extremely aggressive and yet lack of cure. The cellular and molecular mechanism of the aggressiveness remains to be fully elucidated. Our research will provide insights into the understanding of the molecular mechanism of aggressiveness of melanoma and reveal molecular targets for drug development.