Research in the Rosenzweig laboratory is focused identifying new mechanisms and targets in heart failure. Heart failure is closely related to metabolic dysregulation in general and diabetes in particular. In addition to studying what goes wrong in heart disease, a growing area of research has been identification of pathways that keep the heart healthy, using the exercised heart as a model. Earlier studies identified intracellular signaling pathways regulating cardiomyocyte survival and function, including the first demonstration that PI3- kinase and Akt1 are critical in this context. They are also important components in insulin signaling. Subsequent work went on to demonstrate novel targets amenable to pharmacological intervention in heart failure and arrhythmia, such as SGK1, the focus of a recently funded biotech company. Studies of how exercise benefits the heart showed that growth of the heart in response to exercise is fundamentally different from that in response to pathological stimuli such as pressure overload (Cell 2010). Moreover, exercise induces cardiomyogenesis in the adult mammalian heart (Nature Comm 2018). Comprehensive genome-wide analyses have identified candidate pathways that mediate the cardioprotective and regenerative effects of exercise (Cell Metabolism 2015; Circulation 2022). Ongoing efforts seek to exploit the translation potential of targeting these pathways.