We are interested in why the heart fails. Heart failure is an enormous and growing cause of death and disability throughout the world. In addition, the heart provides a model system for studying fundamental cellular processes from cell growth and programmed death, to cell-lineage determination and regeneration.

Recently we’ve been interested in understanding how exercise protects the heart against heart failure. A variety of high throughput profiling techniques are being used to identify pathways differentially regulated in heart growth associated with exercise in comparison to the heart growth that precedes heart failure. These screens have identified interrelated transcriptional pathways (Cell, 2010) and microRNA pathways (Cell Metabolism, 2015), which appear to mediate many of the phenotypic effects of exercise in vivo. In vivo gain- and loss-of-function models are being used to explore the functional effects and molecular mechanisms of this pathway in more detail.

we have been interested in another member of this family, the serine-threonine kinase SGK1, which is activated in diseased but not exercised hearts. We’ve found that genetic inhibition of SGK1 has profound protective effects in the heart, which has prompted a computational small molecule screen to identify SGK1 inhibitors. We are now interested in understanding the upstream and downstream pathways involved in SGK1’s effects in the heart.