Contact Information
Office: E315 GH
Phone: 319-356-4991
Faculty Profile
Brief description of current research:
In the metabolic syndrome, there is a strong association between diabetes mellitus and hypertension. However, little is known about the mechanisms that underlie this association. Our work focuses on the epithelial Na+ channel ENaC, which functions as a pathway for Na+ absorption in the kidney, and as a receptor for salt taste in the tongue. ENaC mutations cause genetic forms of hypertension (Liddle’s syndrome) and hypotension (PHA I), and defects in ENaC regulation are responsible for many of the known genetic forms of hypertension. ENaC is also a downstream target for signaling pathways that are defective in diabetes. Our goal is to elucidate mechanisms that regulate ENaC and to understand how defects in this regulation cause hypertension and other diseases of Na+ transport, including cystic fibrosis. Using a combination of molecular, biochemical, electrophysiological, and whole-animal approaches, our research investigates molecular mechanisms that regulate ENaC trafficking within the cell, and the mechanisms by which ENaC senses and responds to changes in its external environment through changes in channel gating. The eventual goal of this work is to translate our findings to humans in order to develop more targeted and effective treatments for hypertension.
3 most influential diabetes/obesity/metabolism publications:
- Kabra R, Knight KK, Zhou R, Snyder PM: Nedd4-2 induces endocytosis and degradation of proteolytically cleaved epithelial Na+ channels. J Biol Chem, 283:6033-6039, 2008.
- Collier DM, Peterson ZJ, Blokhin IO, Benson CJ, Snyder PM: Identification of extracellular domain residues required for epithelial Na+ channel activation by acidic pH. J Biol Chem, 287(49):40907-14, 2012.
- Zhou, R., Tomkovicz, V.R., Butler, P.L., Ochoa, L.A., Peterson, Z.J., Snyder, P.M.: Ubiquitin Specific Peptidase 8 (USP8) Regulates Endosomal Trafficking of the Epithelial Na+ Channel. J. Biol. Chem. 2013.