B.S. Chemistry (Biochemistry ACS Approved), Western Connecticut State University, 2021
Hypertrophic Cardiomyopathy (HCM) is a mendelian inherited genetic disorder that affects 1 in 500 people globally. HCM is clinically defined by left ventricular hypertrophy (LVH) with potential secondary outcomes such as heart failure (HF) and sudden cardiac death (SCD). Causal mutations predominantly map to genes encoding proteins of the sarcomere, the basic contractile unit of cardiac and skeletal muscle. Of all HCM-causing mutations, one-third of them are in beta myosin, the primary motor protein driving ATP-dependent muscle contraction. HCM-causing mutations have been mapped to all structural domains of beta myosin, including the globular head, neck, and rod. While mutations within the globular head and neck are relatively well studied, the role that rod mutations play in disease development is poorly understood. Furthermore, different missense rod mutations within the same amino acid residue of beta-myosin illicit tissue-specific pathology, as R1500W causes HCM in cardiac tissue, while R1500P causes MPD1, a skeletal myopathy. I am investigating the role that the R1500W mutation has on the metabolic and energetic landscape within cardiac and skeletal muscle. Using a variety of models such as iPSC-derived cardiomyocytes, myocytes, and transgenic mice, I aim to elucidate the role that rod mutations have in HCM pathology and the driving force for tissue specificity.