Unraveling the molecular mechanisms driving mechanical dysfunction in heart disease requires a system capable of precision tuning of the mechanical environment during long-term culture that is compatible with genetic and pharmaceutical therapies and advanced characterization techniques (microscopy). Our lab leverages ECT technology to study the long-term consequences of mechanical stress on cardiac remodeling as well as to evaluate the potential efficacy of therapeutic interventions. We are also focused in developing this technology so that it can more accurately simulate real conditions of cardiac function and stress.

Human heart disease is multifactorial and develops over decades, essentially meaning that no two hearts behave the same. This can be seen in family members carrying heart-disease causing mutations where one family member develops heart failure early in life and another never does. Little is known about the molecular mechanisms that give rise to this divergence, but they key to preventing patients with known cardiac mutations from developing heart failure. Our lab is extremely interested in developing tools that can be taken from bedside to benchtop and back. To this end, we employ computational tools to correlate mechanical and functional differences in patient tissue with clinical data to determine how changes at the molecular level manifest in patient quality of life. The dream is that as we refine our ability to mimic cardiac function in biopsy preparations we will have a predictive tool that can be used to test patient tissue and directly personalize therapeutic strategies.

Extracellular matrix remodeling in heart failure is progressive and contributes to both systolic and diastolic dysfunction. Cardiomyocytes directly “feel” their ECM and respond to remodeling by changing their contractile performance that feeds forward to promote further ECM remodeling. No existing therapies target this run-away train in heart failure, largely because the molecular regulators are poorly understood. Our lab is using the ECT platform which allows precise tuning of ECM composition to dissect the factors that drive pathological remodeling of the cardiomyocyte.

Having recently demonstrated that stabilization of the microtubule network increases cardiomyocyte viscoelasticity and reduces contractile performance in heart failure. Our lab is interested in understanding the molecular mechanisms that give rise to increased microtubule stability in the cardiomyocyte. Depending on the etiology of heart disease, differential regulation of specific microtubule associated proteins (MAPs) changes their affinity for the microtubule network that directly modulate microtubule stability.