Molecular mechanisms of cardiac dysfunction - Pilot Project of the COBRE for the Center for Molecular Medicine

The goal of this 2-year pilot award is to generate 4 publications that will support a major NIH application (a 3 PI R01, or a PPG) focusing on heart failure. The large grant will be submitted in Fall 2016 and will use a multi-scale computer model to integrate experimental data from molecular and cell-level experiments to predict effective therapies for human heart failure. This pilot award will support the main application by testing the hypothesis that increasing the relative phosphorylation of troponin I in sub-epicardial myocardium (the heart’s outer layer) will improve cardiac function in rats with heart failure. The pilot plan leverages the skills of 3 researchers: Kenneth Campbell, PhD (cell and molecular-level experiments), Brandon Fornwalt, MD, PhD (cardiac magnetic resonance imaging), and Jonathan Wenk, PhD (finite element modeling). Aim 1 quantifies cardiac function in rats with heart failure by simultaneously measuring left ventricular pressure and myocardial strain rates. Aim 2 uses these data to validate a new computer model that quantifies how cardiac output is modulated when a specific sarcomeric protein is phosphorylated. Together, these aims will demonstrate that the PIs can xtrapolate data from molecular-level experiments to predict whether therapies can rescue organ-level function.