Heart disease remains the leading cause of death in the United States and other developed countries. Half of these deaths occur suddenly, typically from ventricular tachyarrhythmias that arise in the setting of acute ischemia, acquired heart disease or inherited syndromes including channelopathies and cardiomyopathies. Gap junction channels are responsible for normal impulse propagation and gap junction remodeling contributes to these lethal rhythm disturbances. A detailed understanding of the mechanisms responsible for gap junction remodeling are lacking, preventing the development of anti-arrhythmic strategies targeting the gap junction protein complex. Through the use of genetically engineered mice and novel high throughput genetic screens, we propose a series of experiments to more fully characterize the molecular mechanisms responsible for gap junction remodeling, with the longer term goal of identifying novel therapeutics.
Heart disease is the leading cause of death in the United States and other developed countries and almost half of these deaths occur suddenly from heart rhythm abnormalities. Our research is directed toward understanding the mechanisms responsible for these lethal arrhythmias and identifying potential new therapeutic targets.
|Park, David S; Fishman, Glenn I (2014) Nav-igating through a complex landscape: SCN10A and cardiac conduction. J Clin Invest 124:1460-2|
|Kim, Eugene; Fishman, Glenn I (2013) Designer gap junctions that prevent cardiac arrhythmias. Trends Cardiovasc Med 23:33-8|
|Danielson, Laura S; Park, David S; Rotllan, Noemi et al. (2013) Cardiovascular dysregulation of miR-17-92 causes a lethal hypertrophic cardiomyopathy and arrhythmogenesis. FASEB J 27:1460-7|
|Lader, Joshua M; Vasquez, Carolina; Bao, Li et al. (2011) Remodeling of atrial ATP-sensitive Kýýý channels in a model of salt-induced elevated blood pressure. Am J Physiol Heart Circ Physiol 301:H964-74|
|Remo, Benjamin F; Qu, Jiaxiang; Volpicelli, Frank M et al. (2011) Phosphatase-resistant gap junctions inhibit pathological remodeling and prevent arrhythmias. Circ Res 108:1459-66|
|Bao, Li; Kefaloyianni, Eirini; Lader, Joshua et al. (2011) Unique properties of the ATP-sensitive K? channel in the mouse ventricular cardiac conduction system. Circ Arrhythm Electrophysiol 4:926-35|
|Park, David S; Fishman, Glenn I (2011) The cardiac conduction system. Circulation 123:904-15|
|Levin, Richard I; Fishman, Glenn I (2011) The power of Pasteur's quadrant: cardiovascular disease at the turn of the century. FASEB J 25:1788-92|
|Chin, King-Tung; Kang, Guoxin; Qu, Jiaxiang et al. (2011) The sarcoplasmic reticulum luminal thiol oxidase ERO1 regulates cardiomyocyte excitation-coupled calcium release and response to hemodynamic load. FASEB J 25:2583-91|
|Pallante, Benedetta A; Giovannone, Steven; Fang-Yu, Liu et al. (2010) Contactin-2 expression in the cardiac Purkinje fiber network. Circ Arrhythm Electrophysiol 3:186-94|
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