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.

Public Health Relevance

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.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
2R01HL082727-06A1
Application #
8581597
Study Section
Electrical Signaling, Ion Transport, and Arrhythmias Study Section (ESTA)
Program Officer
Krull, Holly
Project Start
2005-12-01
Project End
2017-05-31
Budget Start
2013-09-01
Budget End
2014-05-31
Support Year
6
Fiscal Year
2013
Total Cost
$403,410
Indirect Cost
$165,410
Name
New York University
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
121911077
City
New York
State
NY
Country
United States
Zip Code
10016
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Remo, Benjamin F; Giovannone, Steven; Fishman, Glenn I (2012) Connexin43 cardiac gap junction remodeling: lessons from genetically engineered murine models. J Membr Biol 245:275-81
Lorentz, R; Shao, Q; Huang, T et al. (2012) Characterization of gap junction proteins in the bladder of Cx43 mutant mouse models of oculodentodigital dysplasia. J Membr Biol 245:345-55
Park, David S; Fishman, Glenn I (2012) Forever young: induced pluripotent stem cells as models of inherited arrhythmias. Circulation 125:3055-6
Giovannone, Steven; Remo, Benjamin F; Fishman, Glenn I (2012) Channeling diversity: gap junction expression in the heart. Heart Rhythm 9:1159-62
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

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