Wesley McKeithan's Research Focus
Wesley is focused on developing high throughput assays that measure cardiomyocyte action potential and calcium transient kinetics. Current methods of evaluating physiology of cardiomyocytes in vitro are tedious and relatively low throughput. Development of an automated optical means to measure physiological parameters will facilitate large-scale screens of small molecules or RNA libraries to elucidate cellular proteins and signaling pathways that control the normal and pathophysiological function of cardiomyocytes, and potentially develop drugs to treat disease symptoms. The primary focus of the project will be to use normal cardiomyocytes in moderate throughput screens to identify a network of microRNAs and proteins that control contractile function. A second focus of the project will be to model the congenital channel disease Long QT type 3, which causes a delay in action potential repolarization, using cardiomyocytes derived from patient-specific induced pluripotent stem cells (iPSCs). This disease is caused by a “leaky” sodium channel and the “disease-in-a-dish” model will be used to optimize a currently proscribed drug in order to remove an undesired off-target effect that causes a potentially lethal arrhythmia in a subset of patients.