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
Wang, JuFang; Song, Jianliang; Gao, Erhe et al. (2014) Induced overexpression of phospholemman S68E mutant improves cardiac contractility and mortality after ischemia-reperfusion. Am J Physiol Heart Circ Physiol 306:H1066-77
Huang, Zheng Maggie; Gao, Erhe; Chuprun, J Kurt et al. (2014) GRK2 in the heart: a GPCR kinase and beyond. Antioxid Redox Signal 21:2032-43
Kim, Il-Man; Wang, Yongchao; Park, Kyoung-Mi et al. (2014) *-arrestin1-biased *1-adrenergic receptor signaling regulates microRNA processing. Circ Res 114:833-44
Brinks, Henriette; Giraud, Marie-Noelle; Segiser, Adrian et al. (2014) Dynamic patterns of ventricular remodeling and apoptosis in hearts unloaded by heterotopic transplantation. J Heart Lung Transplant 33:203-10
Shinozaki, Shohei; Chang, Kyungho; Sakai, Michihiro et al. (2014) Inflammatory stimuli induce inhibitory S-nitrosylation of the deacetylase SIRT1 to increase acetylation and activation of p53 and p65. Sci Signal 7:ra106
Woodall, Meryl C; Ciccarelli, Michele; Woodall, Benjamin P et al. (2014) G protein-coupled receptor kinase 2: a link between myocardial contractile function and cardiac metabolism. Circ Res 114:1661-70
Brady, Donita C; Crowe, Matthew S; Turski, Michelle L et al. (2014) Copper is required for oncogenic BRAF signalling and tumorigenesis. Nature 509:492-6
Bathgate-Siryk, Ashley; Dabul, Samalia; Pandya, Krunal et al. (2014) Negative impact of *-arrestin-1 on post-myocardial infarction heart failure via cardiac and adrenal-dependent neurohormonal mechanisms. Hypertension 63:404-12
Scimia, Maria Cecilia; Blass, Benjamin E; Koch, Walter J (2014) Apelin receptor: its responsiveness to stretch mechanisms and its potential for cardiovascular therapy. Expert Rev Cardiovasc Ther 12:733-41
Weber, C; Neacsu, I; Krautz, B et al. (2014) Therapeutic safety of high myocardial expression levels of the molecular inotrope S100A1 in a preclinical heart failure model. Gene Ther 21:131-8

Showing the most recent 10 out of 103 publications