Proteomic Analysis of Mitochondrial and Sarcomeric Proteins in Cardiomyopathy

Type of Award: Catalyst
Award Number:
Award Period: January 2008 - December 2008
Amount Awarded: $ 199,992.00
PI(s): E. McNally, MD, PhD, UChicago; P. Schumacker, PhD, NU; R. J. Solaro, PhD, UIC; H. Ardehali, NU;

Abstract: Heart Failure is a major epidemic in the developed world. More than 5 million Americans are diagnosed with this disorder and our annual expenses related to heart failure approaches $38 billion. Cardiomyopathy (CM) is defined as the inability of the heart to deliver adequate blood flow to the body and generally leads to heart failure. Although we have made significant progress in diagnosing and treating CM, the molecular pathogenesis of this disorder is not totally understood. This is to a great extent due to limited collaboration among groups that study CM. In June 2006, several lead investigators from UIC, University of Chicago and Northwestern University started the Chicago Cardiac Genomic and Proteomic Center. The purpose of the group was to bring diverse expertise in CM research from different institutions together to start a de novo collaboration and identify the molecular defects in CM. The group has met multiple times since last year and our plans and aims have improved significantly. We hypothesize that the primary defects and triggers of CM are alterations of mitochondrial and sarcomeric proteins as a consequence of excessive oxidative stress. Mitochondria (also called the "powerhouse" of the cell) are organelles that regulate three important cellular processes: 1) generation of energy, 2) mediating cell death and survival in response to injurious insults, and 3) production of molecules that cause oxidative stress on cells. Sarcomeric structures are proteins that mediate force generation by the heart cells and cause beating of the heart. In this proposal, we will use novel techniques to study whether modifications occur in mitochondrial and sarcomeric proteins in animal models of CM. We will then apply the knowledge obtained from these studies to perform genetic analysis in patients with CM. These studies would not be possible without close collaboration among the involved groups. We believe CCGPC will build the infrastructure to make Chicago the leading heart failure research center in the world. The CCGPC is in the process of applying to Center Grants and invited grants from the National Institute of Health and would use the CBC award as a catalyst for these larger Center Awards.