My laboratory is focused on better understanding the pathways driving biomechanical stress responses in cardiac muscle as they are major triggers for human genetic-based cardiac diseases. More recently, our major efforts have centralized on complexes at the cardiac muscle cell-cell junction as genetic mutations/deficiencies in components associated with this complex drive the devastating “athlete’s” heart muscle disease, arrhythmogenic right ventricular cardiomyopathy (ARVC), that results in sudden death. We exploit genetically engineered mouse models and induced pluripotent stem cells (iPSCs) from human patients, miniaturized physiological assays, and a range of molecular and cell biological techniques, including yeast-two-hybrid screens to uncover novel protein interactions that may drive cardiac disease pathogenesis. Through collaborations with prominent investigators in the bioengineering/nanoengineering departments, we have exploited in vitro model systems (eg. aligned cardiomyocyte mouse models, co-culture devices, specialized cardiac extracellular matrix coatings, 3D printing) that have uncovered early mechanisms and unconventional roles for cell-cell junction proteins in cardiac muscle, conduction, maturity and human cardiac disease. In this manner, we are developing a comprehensive understanding of the complex role for the cell-cell junction network and its requirement for optimal cardiac function both in vitro and in vivo.