Anne M. Murphy, MD
Translational Proteomics in Hypertrophic Cardiomyopathy
Johns Hopkins University, Baltimore, MD
2014 Amount Awarded – $50,000
Hypertrophic cardiomyopathy (HCM) is the leading cause of sudden death in young athletes. Symptoms include irregular heart rhythms, difficulty with exercise and heart failure; however some individuals who have HCM never develop symptoms. Although research has shown that HCM is primarily caused by mutations in sarcomeric genes, there are variations in how the disease manifests including age of onset, severity of hypertrophy and risk of sudden death even within a family with the same genetic mutation. One cause of HCM is when only one copy of a gene for a heart muscle motor protein is abnormal. The study will focus on measuring the exact quantity of the abnormal protein as well as the protein that is produced by the normal gene copy in heart muscle. This may help predict who might be at risk of symptoms and increased disease severity from greater amounts of abnormal protein. The results would serve as predictive biomarkers for classifying patient risk for poor outcome and lead to protective therapies for high-risk patients. Another factor that can affect how the heart pumps in HCM is how individual heart motor proteins are modified by a chemical change called phosphorylation in comparison to normal heart. Abnormal phosphorylation of troponin I is known to alter heart relaxation. This study will use a cutting edge "proteomics" technique to measure changes in phosphorylation at every site in this key protein for muscle regulation. Proteomic and phosphoproteomic studies will be performed on cardiac muscle from patients who undergo septal myectomy or transplantation. By determining how phosphorylation affects muscle function differently, new therapies may be developed to correct abnormal phosphorylation of heart muscle proteins.