Cardiac arrhythmias extract a huge public health cost in morbidity and mortality, they are becoming more prevalent as the population ages, and available drug therapies are only partially effective and cause serious adverse effects, including proarrhythmia. The last decade has seen a quantum increase in our understanding of the molecular mechanisms underlying cardiac arrhythmias, due in large part to identification of the genes whose expression results in pore-forming ion channel subunits. However, as our understanding of arrhythmia mechanisms has advanced, it is becoming clear that electrical activity in the heart is driven not by ion channels alone, but by the complex biologic context in which these channels are expressed. Cloning of human and mouse genomes offers an new opportunity to determine the way in which this context - including components such transcription, protein-protein interactions, and post-translational modification by activation of intracellular signaling - can be disrupted to cause arrhythmias. In this Program, a highly interactive group of scientists propose 5 Projects to test a series of specific hypotheses relating arrhythmia susceptibility to dysfunction of myocyte biology. Themes that cross Projects include studies of decreased channel availability, channel interactions with known and new subunits, and altered channel function by activation of intracellular signaling. Scientific tasks common to multiple Projects will be supported in two Cores: a cellular and mouse surgical Core and a microarray Core. This Program, by applying a new, genomic/systems approach to arrhythmias, will improve available therapies through identification of new targets for risk stratification and for antiarrhythmic intervention.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Program Projects (P01)
Project #
5P01HL046681-13
Application #
6785911
Study Section
Heart, Lung, and Blood Initial Review Group (HLBP)
Program Officer
Wang, Lan-Hsiang
Project Start
1992-08-01
Project End
2007-07-31
Budget Start
2004-08-01
Budget End
2005-07-31
Support Year
13
Fiscal Year
2004
Total Cost
$1,174,596
Indirect Cost
Name
Vanderbilt University Medical Center
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
004413456
City
Nashville
State
TN
Country
United States
Zip Code
37212
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