Xander Wehrens Lab

Current major projects in the lab focus on the molecular basis of inherited arrhythmia syndromes like catecholaminergic polymorphic ventricular tachycardia (CPVT), congenital long QT syndrome (LQTS), and Wolff-Parkinson-White syndrome (WPW), as well as other more complex, multifactorial cardiac diseases like atrial fibrillation and hypertrophic cardiomyopathy. These translational studies are aimed at developing new therapeutic targets for heart disease.

Proper contraction and relaxation of the heart depends on the coordinated flux of calcium ions in and out of individual cardiac muscle cells. Research in our lab focuses on understanding how these calcium dynamics are regulated in normal and diseased hearts, and how abnormal intracellular calcium release may contribute to the development of cardiac arrhythmias, hypertrophy, and heart failure.

We are particularly interested in the genetic and posttranslational regulation of key molecules involved in intracellular calcium handling, including the ryanodine receptor type 2 (RyR2), striated muscle preferentially expressed protein kinase (SPEG), junctophilin-2 (JPH2), and nucleoside-diphosphate kinase (NDPK). In addition, we study the paracrine signaling interactions between cardiac fibroblasts and myocytes, and their role in profibrotic signaling.

New therapies in development include small molecule inhibitors of the RyR2 calcium release channel and gene therapy vectors for CRISPR/Cas9-mediated genome editing.