Peter J. Mohler, Ph.D.
110G DHLRI; 473 West 12th Avenue
General Research Interest
Our research focuses on the molecular mechanisms underlying ion channel and transporter targeting in cardiac and other excitable cells. In particular, we are interested in the role of membrane-associated ankyrin family of polypeptides in the targeting and function of ion channels and transporters. One line of our work has established that loss-of-function mutations in ankyrin-B is the basis for a new human cardiac arrhythmia syndrome associated with sinus node dysfunction, repolarization defects, and polymorphic tachyarrhythmia in response to stress and/or exercise (“ankyrin-B syndrome”).
A second line of work in the lab is focused on the role of ankyrin-G for targeting voltage-gated Na channels in heart. These studies establish a physiological requirement for ankyrins in localization of a variety of ion channels in excitable membranes in the heart and demonstrate a new class of functional ‘channelopathies’ due to abnormal cellular localization of functionally-related ion channels and transporters.
A third line of work involves the role of ankyrin-B in the regulation of insulin secretion. Our studies identified a key binding partner for ankyrin-B in the pancreatic beta cell, the KATP channel. This channel serves as a metabolic sensor that regulates insulin secretion. Ankyrin-B is necessary not only for the targeting of this channel to the plasma membrane, but also for the ability of the channel to respond to changes in the metabolic state of the cell. We identified a known human mutation in a KATP channel gene that disrupts the ankyrin-B interaction, resulting in permanent neonatal diabetes mellitus (PNDM).
Faith Kline, Ph.D.
Research Associate, Lab Manager
Jingdong Li, M.D.
Farshid Kashef, M.D.
Lan Qian, Ph.D.
Jerry Curran, Ph.D.