Despite modern practices, heart failure remains an important cause of morbidity and mortality worldwide. The overarching goal of our laboratory is to identify disease mechanisms that contribute to the pathogenesis of heart failure and design novel strategies to effectively treat these important diseases. To tackle these challenging issues we have focused our efforts on two poorly understood areas with limited available therapies.
Precision Therapies for Heart Failure
For patients with dilated cardiomyopathies, little is known regarding precise mechanisms by which genetic variants result in heart failure and by what extent these mechanisms may vary between different genetic etiologies. To approach this problem and define precision therapeutics for dilated cardiomyopathy, we utilize Zebrafish and Mouse models in conjunction with advanced imaging and high throughput chemical screening platforms.
Immune Cell Heterogeneity and Ontogeny
Independent of the cause of heart failure once patients develop heart failure, the majority of individuals will experience disease progression and eventually progress to end-stage disease. However, a small number of patients will experience disease remission and may spontaneously recover cardiac function. To define the mechanisms that dictate whether a patient will experience disease progression or recover from heart failure, we have focused on understanding how the innate immune system influences the heart’s response to acute and chronic tissue injury. Through these studies we have discovered that the heart contains a diverse and heterogeneous complement of immune cells derived from divergent embryonic origins with unique reparative and inflammatory functions. Current projects in the laboratory are focused on understanding the exact origins of these cells in the mouse and human heart, identifying molecular determinants of cell fate, and deciphering mechanisms by which each cell type is mobilized, activated and mediates its effector functions during development, disease, and regeneration.