University of Pittsburgh

My primary research interest is in the regulation of the Epithelial Sodium Channel (ENaC). Research focuses on ENaC regulation in two systems, the distal kidney nephron and airway epithelia. Investigations are carried out on kidney cortical collecting duct cells to elucidate the mechanism of acute (minute time-scale) upregulation of ENaC in response to cAMP stimulation, and the fate of ENaC following withdrawal of this stimulation. From this work we identified and characterized an intracellular vesicular recycling pool responsible for targeted exocytic insertion of ENaC into the apical membrane. Research is now focused on understanding the intracellular pathways responsible for returning ENaC to this recycling vesicle pool. In separate, but related studies, primary human bronchiolar epithelia cultures are used to characterize ENaC regulation in the distal airway. Little is known about the mode of ENaC regulation in these cells, in particular mechanisms which may contribute to disease states like cystic fibrosis. We make use of a range of electrophysiological techniques to measure ion transport in polarized epithelial monolayers. In addition we have developed both live cell and membrane-isolated fluorescent imaging techniques to investigate the regulation of ENaC in these polarized cultures. By comparing ENaC regulation in two distinct cell systems, areas of common and divergent regulation can been established.