research overview
- My lab has a long-standing interest in genetic diseases of the heart caused by mutations in the motor protein myosin. 500 mutations in the 10-member striated muscle myosin gene family cause a variety of cardiac and skeletal muscle myopathies. We research how such mutations cause disease using multiscale systems ranging from single molecule functional measurement in vitro, cell-based systems using cardiomyocytes, engineered heart tissues, genetically modified mice, and human heart tissues. We have intriguing data about an unorthodox myosin, MYH7b that is not expressed in specialized striated muscles, but also in the brain and inner ear. Mutations in MYH7b cause hereditary hearing loss but by unknown mechanisms. We have also recently discovered, through single molecule imaging that myosin molecules travel in and out of sarcomeres very frequently and we are studying the significance of this shuttling and how myosin mutations affect this process. As always, we continue to investigate how myosin mutation effects and muscle adaptations to different stimuli differ in male and female hearts and cardiac myocytes. We also have a large program studying pythons' novel biology that they evolved to survive extreme environments and how this can be translated to promote human health. More recently, we have turned to understanding how muscles and the heart maintain protein quality control in health and disease. Since cardiomyocytes are as old as the organism, this is particularly challenging.
