Peter J. Mohler, Ph.D.

Associate Professor of Medicine and
Molecular Physiology & Biophysics

University of North Carolina at Chapel Hill, 2000, Ph.D.
Howard Hughes Medical Institute, Duke University,
Durham, NC, Post-doc, 2000-2004

Research Interests

A number of serious human genetic diseases, including fatal cardiac arrhythmias, cystic fibrosis, Liddle's syndrome, and epilepsy are caused by abnormal targeting and expression of ion channel and transporters at specialized membrane domains. 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.

Our recent work establishes that loss-of-function mutation in ankyrin-B is the basis for a new human cardiac arrhythmia syndrome associated with bradycardia, abnormal heart rate variability, repolarization defects, and polymorphic tachyarrhythmia in response to stress and/or exercise. Additionally, our work revealed that reduction of ankyrin-B in mice results in reduced levels and abnormal localization of Na/Ca exchanger, Na/K ATPase, and InsP₃ receptor at T-tubule/SR sites in cardiomyocytes and leads to altered Ca²⁺ signaling and extrasystoles that provide a rationale for the arrhythmia. These studies establish a physiological requirement for ankyrins in localization of a variety of ion channels in excitable membranes in the heart and suggest a new class of functional 'channelopathies' due to abnormal cellular localization of functionally-related ion channels and transporters.

Selected Publications

Mohler PJ, JA Healy, H Xue, AA Puca, CF Kline, RR Allingham, EG Kranias, HA Rockman, and V Bennett. Ankyrin-B Syndrome: Enhanced cardiac function balanced by Risk of Cardiac Death and Premature Senescence. Public Library of Science (PLoS) One. 2(10):e1051. 2007.

Mohler PJ and XHT Wehrens. Mechanisms of human arrhythmia syndromes: Abnormal cardiac macromolecular interactions. Physiology. 22:342-50. 2007.

Mohler PJ, MY Zhu, AM Blade, AJ Ham, GS Shelness, and LL Swift. Identification of a novel isoform of microsomal triglyceride transfer protein. The Journal of Biological Chemistry, 282 (37): 26981-26988. 2007.

Anderson ME and PJ Mohler. MicroRNA may have macro effect on sudden death. Nature Medicine. 13: 410-411; 2007.

Bhasin N, SR Cunha, M Mudannayake, MS Gigena, TB Rogers, and PJ Mohler. Molecular basis for PP2A regulatory subunit B56 alpha targeting in cardiomyocytes. American Journal of Physiology: Heart and Circulatory Physiology. 293 (1) H109-119; 2007.

Cunha SR, N Bhasin, and PJ Mohler. Targeting and stability of the Na/Ca exchanger in cardiomyocytes requires direct interaction with the membrane adaptor ankyrin-B. The Journal of Biological Chemistry 282 (7): 4875-4883; 2007.