In the research laboratory, we are examining factors that regulate kidney (or renal) sodium excretion, with special focus on the epithelial sodium channel (ENaC). Increased ENaC activity reduces the sodium excreted in the urine. Using a combination of electrophysiology, animal modeling, and human clinical data we are exploring the roles played by ENaC in regulating sodium excretion and blood pressure in healthy and diseased kidneys. We are examining whether genetic polymorphisms in the genes encoding ENaC alter blood pressure. In experimental systems, ENaC can be activated by extracellular proteases. We are exploring the importance of proteolytic activation of ENaC in vivo in normal physiology and in diseased kidneys. For example, in nephrotic syndrome, a disorder in which damaged kidneys leak blood stream proteins into the urine, it is possible that blood stream proteases such as plasmin activate ENaC in the kidney, reducing excretion of sodium. We are exploring these and other mechanisms of regulation of ENaC. Finally, because ENaC is also expressed in the lung, colon, tongue, blood vessels and brain, we are examining what physiologic roles ENaC plays in sodium transport in these organ systems.