Hund Receives Five-Year NIH Award.

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Assistant Professor Thomas Hund has received a five-year grant of $1.9M from the National Institute of Health (NIH), for the project entitled "CaMKII-dependent regulation of cardiac excitability." Cardiac electrical disturbances (arrhythmias) are responsible for most of the 400,000 heart related deaths each year in the United States. At the cellular level, abnormal membrane excitability increases susceptibility to potentially fatal cardiac arrhythmias. These studies will identify molecular pathways for regulation of cell membrane excitability in heart and will generate new insight into mechanisms underlying congenital and common acquired forms of cardiac arrhythmia.

Reseach Abstract:

Excitable cell function depends on highly evolved local signaling domains that exert tight spatial and temporal control over post-translational modification (e.g. phosphorylation, oxidation) of ion channels, transporters and receptors. Disruption of these local signaling domains and/or alterations in post-translational modification of membrane proteins are associated with increased susceptibility to arrhythmia in congenital and acquired forms of heart disease, including heart failure. Calmodulin kinase II is a multifunctional serine/threonine kinase that regulates a broad spectrum of critical cellular functions in heart. Despite the importance of calmodulin kinase II for heart function, little is known regarding the biogenesis of local domains to control signaling.  Our research seeks to understand the cellular pathways responsible for local calmodulin kinase II-dependent regulation of membrane proteins in specific subcellular domains with the overall objective of generating new insight into human cardiac arrhythmia and sudden death. Our studies will test the central hypothesis that the actin-associated polypeptide betaIV-spectrin organizes a local membrane domain at the cardiomyocyte intercalated disc to control phosphorylation of the cardiac voltage-gated sodium channel, and that this spectrin-based complex is critical for regulating channel function in diverse forms of cardiac disease associated with arrhythmias and sudden death. We anticipate that this research will generate new insight into organization of calmodulin kinase II signaling domains, define molecular pathways for regulation of voltage-gated sodium channels and cell excitability, and identify novel mechanisms for arrhythmias in both congenital and acquired heart disease.   

Congratulations Dr. Hund!

 

Click here more details of this NIH-funded research.