Human diseases associated with altered calcium signaling in muscle and neurons
My research focuses on acquiring a better understanding of calcium channel function and protein interactions involved in calcium signaling in muscle and neurons. Calcium serves as a second messenger in many cellular functions throughout the nervous system and in skeletal and cardiac muscle. As a result of the diverse roles of calcium ions in cellular function, genetic mutations in calcium channels can affect not only the electrical activity of cells but also diverse downstream signaling. Mutations of genes encoding calcium have been implicated in the etiology of a diverse group of nerve and muscle diseases. Calcium channel defects are responsible for inherited human disorders of skeletal muscle (including hypokalemic periodic paralysis, malignant hyperthermia and central core disease), and of cardiac muscle (arrhythmogenic right ventricular cardiomyopathy type-2 and familial polymorphic ventricular tachycardia). Neuronal calcium channels have been associated with several dominantly-inherited human diseases ranging from visual disorders to migraines, ataxia, and seizures such as familial hemiplegic migraine, cerebellar ataxia-2, congenital night blindness, generalized epilepsy, and absence seizures. In addition, disruption in calcium homeostasis has been implicated in the pathology of several other human diseases that are not directly due to mutations in calcium-regulating proteins; for example, spinocerebellar ataxia 1, 2 and 3, Alzheimer's disease, amyotrophic lateral sclerosis, Huntington's disease, and Parkinson's disease. Research in my lab incorporates a multi-faceted approach combining electrophysiology, confocal microscopy, calcium imaging and molecular biology. The information gained through these functional studies will be critical not only for understanding an essential function in muscular and nervous systems, but also for determining how mutational alterations of calcium channels lead to human disease, and for developing therapeutic approaches for these diseases.