Myosin Binding Protein C structure-function relationships in the failing heart

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DESCRIPTION (provided by applicant): Congestive heart failure (CHF) is associated with an abnormality in cardiac cell function. The molecular mechanisms that underlie this depressed function in CHF are not completely understood. The Major research theme at the Department of Cell and Molecular Physiology at the Loyola University Chicago Stritch School of Medicine is Cardiovascular Research with a special focus on heart failure. The purpose of this proposal is to secure funds to enable hiring of a new Assistant Professor (full time; at least 90% effort dedicated to research) to expand the existing research environment to include studies into heart failure associated malfunction and regulation of thick filament proteins, in particular cardiac Myosin Binding Protein C (cMyoBPC). Mutations in this protein alone are associated with over half of the documented cases of familial hypertrophic cardiomyopathy. In addition, recent data strongly suggest an important role for post-translational modification (phosphorylation) of cMyoBPC in heart failure and ischemia/reperfusion myocardial dysfunction. We have identified a strong candidate who is ready to transition to a junior tenure-track position with a profile that is just right to join our faculty by September 2009. Institutional commitment is secured beyond years 1-2 of this award. Due to the economic downturn, hiring of this promising Assistant Professor in 2009 is in jeopardy. The existing research environment is strong, but would be greatly enhanced by hiring of this candidate. Accurate knowledge regarding the fundamental molecular mechanisms underlying cardiac myocyte dysfunction in heart failure is expected to form the basis for the development of new therapeutic strategies to combat this devastating syndrome. Heart failure is a leading cause of mortality and morbidity is associated with maladaptation of many aspects of cardiac function, including dysfunction of contractile proteins. The purpose of this proposal is to make possible hiring of a new Asst. Prof, to study cardiac Myosin Binding Protein C in health and disease.