The focus of our laboratory is to understand the molecular mechanisms of hypertrophy and heart failure. To achieve this goal, our laboratory uses a number of animal models, including mouse and Drosophila, to determine the molecular and genetic basis of heart failure. Strategies that combine state-of-the-art molecular and genetic techniques with sophisticated cardiac phenotyping are routinely used.
Areas of Research
- Signaling: G protein-coupled receptor signaling in hypertrophy and heart failure, focusing on the interaction of phosphoinositide-3 kinase with ß-adrenergic receptors.
- Identification of genetic modifiers of heart failure: Quantitative Trait Loci mapping to identify genetic modifiers of heart failure using sensitized mouse models of heart failure. Genetic screens in mutagenized mice and Drosophila deletion mutants. Candidate genes identified in the mouse are then tested in association-outcome studies in patients with severe heart failure.
- Molecular physiology: In-depth physiological analysis of cardiac function in genetically altered mice to understand the role of G protein-coupled receptor signaling pathways on the development of heart failure in vivo.
- Tachibana H, Naga Prasad SV, Lefkowitz RJ, Koch, WJ, Rockman HA. Level of βARK1 inhibition determines the degree of cardiac dysfunction following chronic pressure overload induced heart failure. Circulation 2005:111;591-597.
- Perrino C, Naga Prasad SV, Schroder JN, Hata JA, Milano C, Rockman HA. Targeted disruption of the β adrenergic receptor kinase 1/phosphoinositide 3-kinase complex restores contractile function in heart failure. Circulation2005:111;579-2587.
- Naga Prasad SV, Jayatilleke A, Madamanchi A, Rockman HA. Protein kinase activity of phosphoinositide 3-kinase regulates β-adrenergic receptor endocytosis. Nature Cell Biol. 2005:7;785-796.
- Perrino C, Naga Prasad SV, Mao L, Noma T, Yan Z, Kim HS, Smithies O, Rockman HA. Intermittent pressure overload triggers hypertrophy-independent cardiac dysfunction and vascular rarefaction. J Clin Invest. 2006:116;1547-1560.
- Wolf MJ, Amrein H, Izatt JA, Choma MA, Reedy MC, Rockman HA. Drosophila as a model for the identification of genes causing adult human heart disease. Proc Natl Acad Sci USA 2006:103;1394-1399.
Howard A. Rockman, MD, Director
Office: 226 Clinical Research Lab Building, Durham, NC, 27710
Campus mail: DUMC Box 3104, Durham, NC, 27710