Orson W. Moe, M.D.
Professor of Internal Medicine and Physiology
Director, Charles and Jane Pak Center for Mineral Metabolism and Clinical Research

The major focus of the Moe laboratory is to study the mechanisms of regulation of the principal sodium transporter in the kidney, Na /H exchanger type 3 (NHE3). Normal NHE3 function and regulation are essential for the maintenance of normal extracellular fluid volume, blood pressure and acid-base balance. All the following projects are currently involving or will involve trainees:

Regulation of NHE3. Role of protein trafficking. NHE3 can be acutely regulated by alterations in endocytotic retrieval or exocytotic insertion into the membrane. We are currently studying the regulation of both of these trafficking events. We have recently uncovered a non-genomic mechanism of activation of NHE3 by glucocorticoid hormones through NHE3 exocytosis.

Regulation of NHE3.Role of phosphorylation and binding proteins. Phosphorylation of NHE3 is necessary but insufficient to affect its regulation. We propose that regulatory cofactors are crucial to modulate the phosphorylated protein. We are using multiple approaches to isolate these protein factors. The figure shows one such interacting partner which is calcineurin homologous protein (CHP). CHP-1 interacts with NHE3 and is responsible for mediating the regulation of NHE3 by adenosine.