Introduction: Changes in protein expression and post-translational modifications (PTMs) are essential mechanisms for biological regulation in normal physiology and numerous diseases, including those of the cardiovascular disease [1-4]. Characterizing these changes can provide valuable information for the elucidation of disease etiology, identification of clinically useful biomarkers, and development of novel therapeutics. Thus, methods for the identification of proteins and characterization of protein PTMs are essential to modern biomedical research. In recent years, mass spectrometry (MS)-based proteomics has become the technology of choice for these purposes. MS-based proteomics takes advantage of the modern mass spectrometer's superior resolution power and accuracy in peptide sequencing [5]. It allows for the rapid, large-scale identification and quantification of proteins and their PTMs in multiprotein complexes, whole cells, tissues and organisms with sub-femto mole level sensitivity (100-1000 times more sensitive than traditional technologies). Recently, MS combined with stable isotope labeling technologies (i.e. quantitative proteomics) has emerged as a powerful tool to quantitatively assess dynamic changes in protein expression, subcellular compartmentalization and PTMs on a proteome-wide scale [6]. Therefore, MS-based proteomics is unequaled as a tool for studying complex biological systems and disease in the post-genomic era. All these various tools are particularly applicable to cardiovascular research and should allow us to carry out the goals of this PPG. The ability to deliver genes efficiently to cultured cardiomyocytes and in vivo to the rodent heart is critical to many of the experiments described in the three PPG projects. Viral vectors offer greater transduction efficiency to cultured cardiomyocytes than nonviral methodology such as plasmid DNA delivery via liposomal reagents, electroporation or nucleofector techniques [7]. Similarly, viral vectors are more efficient than non-viral gene delivery methods in mediating gene delivery in vivo to the heart [8]. The Viral Vector Core will provide adenoviral and adeno-associated viral vector development, manufacturing, purification, and validation services to this PPG.

Agency
National Institute of Health (NIH)
Type
Research Program Projects (P01)
Project #
5P01HL075443-10
Application #
8687718
Study Section
Heart, Lung, and Blood Program Project Review Committee (HLBP)
Project Start
Project End
Budget Start
Budget End
Support Year
10
Fiscal Year
2014
Total Cost
Indirect Cost
Name
Duke University
Department
Type
DUNS #
City
Durham
State
NC
Country
United States
Zip Code
27705
Abraham, Dennis M; Davis 3rd, Robert T; Warren, Chad M et al. (2016) β-Arrestin mediates the Frank-Starling mechanism of cardiac contractility. Proc Natl Acad Sci U S A 113:14426-14431
Hullmann, Jonathan; Traynham, Christopher J; Coleman, Ryan C et al. (2016) The expanding GRK interactome: Implications in cardiovascular disease and potential for therapeutic development. Pharmacol Res 110:52-64
Zhang, Rongli; Hess, Douglas T; Reynolds, James D et al. (2016) Hemoglobin S-nitrosylation plays an essential role in cardioprotection. J Clin Invest 126:4654-4658
Woodall, Meryl C; Woodall, Benjamin P; Gao, Erhe et al. (2016) Cardiac Fibroblast GRK2 Deletion Enhances Contractility and Remodeling Following Ischemia/Reperfusion Injury. Circ Res 119:1116-1127
Feldman, Arthur M; Gordon, Jennifer; Wang, JuFang et al. (2016) BAG3 regulates contractility and Ca(2+) homeostasis in adult mouse ventricular myocytes. J Mol Cell Cardiol 92:10-20
Adachi, Naoko; Hess, Douglas T; McLaughlin, Precious et al. (2016) S-Palmitoylation of a Novel Site in the β2-Adrenergic Receptor Associated with a Novel Intracellular Itinerary. J Biol Chem 291:20232-46
Hodavance, Sima Y; Gareri, Clarice; Torok, Rachel D et al. (2016) G Protein-coupled Receptor Biased Agonism. J Cardiovasc Pharmacol 67:193-202
Waldschmidt, Helen V; Homan, Kristoff T; Cruz-Rodríguez, Osvaldo et al. (2016) Structure-Based Design, Synthesis, and Biological Evaluation of Highly Selective and Potent G Protein-Coupled Receptor Kinase 2 Inhibitors. J Med Chem 59:3793-807
Carr 3rd, Richard; Schilling, Justin; Song, Jianliang et al. (2016) β-arrestin-biased signaling through the β2-adrenergic receptor promotes cardiomyocyte contraction. Proc Natl Acad Sci U S A 113:E4107-16
Watson, Lewis J; Alexander, Kevin M; Mohan, Maradumane L et al. (2016) Phosphorylation of Src by phosphoinositide 3-kinase regulates beta-adrenergic receptor-mediated EGFR transactivation. Cell Signal 28:1580-92

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