Howard Rockman

Summary

Affiliation: Duke University Medical Center
Country: USA

Publications

  1. pmc beta-Arrestin-dependent activation of Ca(2+)/calmodulin kinase II after beta(1)-adrenergic receptor stimulation
    Supachoke Mangmool
    Department of Medicine, Duke University Medical Center, Durham, NC 27710, USA
    J Cell Biol 189:573-87. 2010
  2. pmc Phosphoinositide 3-kinase regulates beta2-adrenergic receptor endocytosis by AP-2 recruitment to the receptor/beta-arrestin complex
    Sathyamangla V Naga Prasad
    Department of Medicine, Duke University Medical Center, Durham, NC 27710, USA
    J Cell Biol 158:563-75. 2002
  3. ncbi request reprint Seven-transmembrane-spanning receptors and heart function
    Howard A Rockman
    Departments of Medicine and Cell Biology, Duke University Medical Center, Durham, North Carolina 27710, USA
    Nature 415:206-12. 2002
  4. pmc Intermittent pressure overload triggers hypertrophy-independent cardiac dysfunction and vascular rarefaction
    Cinzia Perrino
    Duke University Medical Center, Durham, North Carolina 27710, USA
    J Clin Invest 116:1547-60. 2006
  5. ncbi request reprint Genetic alterations that inhibit in vivo pressure-overload hypertrophy prevent cardiac dysfunction despite increased wall stress
    Giovanni Esposito
    Department of Medicine, Duke University Medical Center, Durham, NC 27710, USA
    Circulation 105:85-92. 2002
  6. ncbi request reprint Imaging methods for morphological and functional phenotyping of the rodent heart
    Cristian T Badea
    Center for In Vivo Microscopy, Duke University Medical Center, Durham, North Carolina 27710, USA
    Toxicol Pathol 34:111-7. 2006
  7. pmc Cardiac micro-computed tomography for morphological and functional phenotyping of muscle LIM protein null mice
    Cristian T Badea
    Center for In Vivo Microscopy, Department of Radiology, Duke University Medical Center, Durham, NC, USA
    Mol Imaging 6:261-8. 2007
  8. ncbi request reprint Redefining heart failure: the utility of genomics
    Mark P Donahue
    Duke University Medical Center Department of Medicine, Division of Cardiovascular Medicine, Durham, North Carolina 27710, USA
    J Am Coll Cardiol 48:1289-98. 2006
  9. pmc β-Arrestin mediates oxytocin receptor signaling, which regulates uterine contractility and cellular migration
    Chad A Grotegut
    Div of Maternal Fetal Medicine, Dept of Obstetrics and Gynecology, Duke University School of Medicine, Durham, NC 27710, USA
    Am J Physiol Endocrinol Metab 300:E468-77. 2011
  10. ncbi request reprint QTL mapping in a mouse model of cardiomyopathy reveals an ancestral modifier allele affecting heart function and survival
    Ferrin C Wheeler
    Department of Molecular Genetics and Microbiology, Duke University Medical Center, CARL Building Room 265, DUMC 3175, Durham, North Carolina 27710, USA
    Mamm Genome 16:414-23. 2005

Research Grants

  1. BETA ADRENERGIC RECEPTOR PHOSPHORYLATION--HEART FAILURE
    Howard Rockman; Fiscal Year: 2003
  2. MULTIDISCIPLINARY HEART AND VASCULAR DISEASES
    Howard Rockman; Fiscal Year: 2007
  3. MECHANISMS OF MALADAPTATION IN HEART FAILURE
    Howard Rockman; Fiscal Year: 2003
  4. Modifier Genes in Heart Failure
    Howard Rockman; Fiscal Year: 2005
  5. MECHANISMS OF MALADAPTATION IN HEART FAILURE
    Howard Rockman; Fiscal Year: 2009
  6. Identifying Cardiomyopathy Genes in Mice and Drosophila
    Howard Rockman; Fiscal Year: 2009
  7. Identifying Cardiomyopathy Genes in Mice and Drosophila
    Howard Rockman; Fiscal Year: 2007
  8. PHENOTYPIC SCREENS FOR CARDIOVASCULAR MUTATIONS IN MICE
    Howard Rockman; Fiscal Year: 2003
  9. MECHANISMS OF MALADAPTATION IN HEART FAILURE
    Howard A Rockman; Fiscal Year: 2010
  10. MECHANISMS OF MALADAPTATION IN HEART FAILURE
    Howard Rockman; Fiscal Year: 2007

Collaborators

Detail Information

Publications74

  1. pmc beta-Arrestin-dependent activation of Ca(2+)/calmodulin kinase II after beta(1)-adrenergic receptor stimulation
    Supachoke Mangmool
    Department of Medicine, Duke University Medical Center, Durham, NC 27710, USA
    J Cell Biol 189:573-87. 2010
    ..The essential role for beta-arrestin and identification of the molecular mechanism by which only beta(1)-ARs and not beta(2)-ARs activate CaMKII significantly advances our understanding of this important cellular pathway...
  2. pmc Phosphoinositide 3-kinase regulates beta2-adrenergic receptor endocytosis by AP-2 recruitment to the receptor/beta-arrestin complex
    Sathyamangla V Naga Prasad
    Department of Medicine, Duke University Medical Center, Durham, NC 27710, USA
    J Cell Biol 158:563-75. 2002
    ....
  3. ncbi request reprint Seven-transmembrane-spanning receptors and heart function
    Howard A Rockman
    Departments of Medicine and Cell Biology, Duke University Medical Center, Durham, North Carolina 27710, USA
    Nature 415:206-12. 2002
    ..Most of these discoveries have focused on the most common type of cardiac receptor - the seven-transmembrane-spanning receptor or G-protein-coupled receptor...
  4. pmc Intermittent pressure overload triggers hypertrophy-independent cardiac dysfunction and vascular rarefaction
    Cinzia Perrino
    Duke University Medical Center, Durham, North Carolina 27710, USA
    J Clin Invest 116:1547-60. 2006
    ..Thus stress-induced activation of pathogenic signaling pathways, not the duration of stress or the hypertrophic growth per se, is the molecular trigger of cardiac dysfunction...
  5. ncbi request reprint Genetic alterations that inhibit in vivo pressure-overload hypertrophy prevent cardiac dysfunction despite increased wall stress
    Giovanni Esposito
    Department of Medicine, Duke University Medical Center, Durham, NC 27710, USA
    Circulation 105:85-92. 2002
    ..Epidemiological data, however, have shown that cardiac hypertrophy is associated with increased mortality, thus casting doubt on the validity of this hypothesis...
  6. ncbi request reprint Imaging methods for morphological and functional phenotyping of the rodent heart
    Cristian T Badea
    Center for In Vivo Microscopy, Duke University Medical Center, Durham, North Carolina 27710, USA
    Toxicol Pathol 34:111-7. 2006
    ....
  7. pmc Cardiac micro-computed tomography for morphological and functional phenotyping of muscle LIM protein null mice
    Cristian T Badea
    Center for In Vivo Microscopy, Department of Radiology, Duke University Medical Center, Durham, NC, USA
    Mol Imaging 6:261-8. 2007
    ..Other sources of errors for micro-CT are also analyzed. Micro-CT can provide the four-dimensional data (three-dimensional isotropic volumes over time) required for morphological and functional phenotyping in mice...
  8. ncbi request reprint Redefining heart failure: the utility of genomics
    Mark P Donahue
    Duke University Medical Center Department of Medicine, Division of Cardiovascular Medicine, Durham, North Carolina 27710, USA
    J Am Coll Cardiol 48:1289-98. 2006
    ..Here we will review genomic evidence to date and how it can and may be considered in the evaluation and management of cardiomyopathies...
  9. pmc β-Arrestin mediates oxytocin receptor signaling, which regulates uterine contractility and cellular migration
    Chad A Grotegut
    Div of Maternal Fetal Medicine, Dept of Obstetrics and Gynecology, Duke University School of Medicine, Durham, NC 27710, USA
    Am J Physiol Endocrinol Metab 300:E468-77. 2011
    ..The development of unique OXTR ligands that prevent receptor desensitization may be a novel approach in the treatment of adverse clinical events secondary to prolonged oxytocin therapy...
  10. ncbi request reprint QTL mapping in a mouse model of cardiomyopathy reveals an ancestral modifier allele affecting heart function and survival
    Ferrin C Wheeler
    Department of Molecular Genetics and Microbiology, Duke University Medical Center, CARL Building Room 265, DUMC 3175, Durham, North Carolina 27710, USA
    Mamm Genome 16:414-23. 2005
    ..Identification of the genes at these QTLs in the mouse will provide novel candidate genes that can be evaluated for their role in human heart failure...
  11. ncbi request reprint Role of beta-adrenergic receptor signaling and desensitization in heart failure: new concepts and prospects for treatment
    Douglas G Tilley
    Department of Medicine Duke University Medical Center Durham, NC 27710, USA
    Expert Rev Cardiovasc Ther 4:417-32. 2006
    ..This review explores the signaling cascades induced by beta-adrenergic receptor activation in normal and desensitized states to provide new insight into the effective treatment of cardiac dysfunction...
  12. pmc Drosophila as a model for the identification of genes causing adult human heart disease
    Matthew J Wolf
    Department of Medicine, Duke University, Durham, NC 27110, USA
    Proc Natl Acad Sci U S A 103:1394-9. 2006
    ....
  13. ncbi request reprint Heart size-independent analysis of myocardial function in murine pressure overload hypertrophy
    Hideyuki Takaoka
    Department of Medicine, Duke University Medical Center, Durham, North Carolina 27710, USA
    Am J Physiol Heart Circ Physiol 282:H2190-7. 2002
    ..These data suggest that the development of cardiac hypertrophy is associated with a heightened contractile state, perhaps as an early compensatory response to pressure overload...
  14. ncbi request reprint Pressure overload selectively up-regulates Ca2+/calmodulin-dependent protein kinase II in vivo
    Josep M Colomer
    Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, North Carolina 27710, USA
    Mol Endocrinol 17:183-92. 2003
    ..We conclude that CaMKII is the multifunctional CaMK most likely to mediate Ca(2+)- dependent protein phosphorylation events in response to TAC-induced cardiac hypertrophy...
  15. pmc Beta-blockers alprenolol and carvedilol stimulate beta-arrestin-mediated EGFR transactivation
    Il Man Kim
    Department of Medicine, Duke University Medical Center, Durham, NC 27710, USA
    Proc Natl Acad Sci U S A 105:14555-60. 2008
    ..Our findings demonstrate that Alp and Car are ligands that not only act as classical receptor antagonists, but can also stimulate signaling pathways in a G protein-independent, beta-arrestin-dependent fashion...
  16. ncbi request reprint JNK1 is required to preserve cardiac function in the early response to pressure overload
    Hideo Tachibana
    Department of Medicine, Cell Biology and Genetics, Duke University Medical Center, Durham, NC 27710, USA
    Biochem Biophys Res Commun 343:1060-6. 2006
    ..These data suggest that JNK1 plays a protective role in response to pressure overload, preventing the early deterioration in cardiac function following an acute increase in afterload...
  17. ncbi request reprint Level of beta-adrenergic receptor kinase 1 inhibition determines degree of cardiac dysfunction after chronic pressure overload-induced heart failure
    Hideo Tachibana
    Departments of Medicine, Duke University Medical Center, Durham, NC 27710, USA
    Circulation 111:591-7. 2005
    ..Because inhibition of betaARK activity is pivotal for amelioration of cardiac dysfunction, we investigated whether the level of betaARK1 inhibition correlates with the degree of heart failure...
  18. ncbi request reprint Network integration of the adrenergic system in cardiac hypertrophy
    Liza Barki-Harrington
    Departments of Medicine, Cell Biology and Molecular Genetics, Duke University Medical Center, DUMC 3104 226 CARL Building, Research Drive, Durham, NC 27710, USA
    Cardiovasc Res 63:391-402. 2004
    ..Understanding the signaling mechanisms of these receptors in the context of the heart is likely to provide a better therapeutic approach towards treatment of heart failure...
  19. pmc Beta1-adrenergic receptors stimulate cardiac contractility and CaMKII activation in vivo and enhance cardiac dysfunction following myocardial infarction
    ByungSu Yoo
    Departments of Medicine, Cell Biology and Molecular Genetics, Duke University Medical Center, Durham, North Carolina 27710, USA
    Am J Physiol Heart Circ Physiol 297:H1377-86. 2009
    ..Moreover, it appears that beta(1)AR signaling is detrimental to cardiac function following MI, possibly through activation of CaMKII...
  20. pmc Inhibition of receptor-localized PI3K preserves cardiac beta-adrenergic receptor function and ameliorates pressure overload heart failure
    Jeffrey J Nienaber
    Department of Medicine, Duke University Medical Center, Durham, North Carolina, USA
    J Clin Invest 112:1067-79. 2003
    ....
  21. ncbi request reprint Differential myocardial gene expression in the development and rescue of murine heart failure
    Burns C Blaxall
    Department of Surgery, Duke University Medical Center, Durham, North Carolina 27710, USA
    Physiol Genomics 15:105-14. 2003
    ..Thus we have identified methodologies that have the potential to be used for predictive genomic profiling of cardiac phenotype, including cardiovascular disease...
  22. pmc TRPC1 channels are critical for hypertrophic signaling in the heart
    Malini Seth
    Department of Medicine, Duke University School of Medicine, Durham, NC, USA
    Circ Res 105:1023-30. 2009
    ..G protein-coupled receptor signaling is known to govern the hypertrophic response through the regulation of ion channel activity and downstream signaling in failing cardiomyocytes...
  23. pmc A role for the thromboxane receptor in L-NAME hypertension
    Helene Francois
    Department of Medicine, Duke University Medical Center, Rm 2018 MSRB II, 106 Research Drive, Durham, NC 27710, USA
    Am J Physiol Renal Physiol 295:F1096-102. 2008
    ..01). Thus, in L-NAME hypertension, TP receptors contribute to elevated blood pressure and cardiac hypertrophy. In this model, TP receptors also provided unexpected protection against kidney injury...
  24. ncbi request reprint Role of phosphoinositide 3-kinase in cardiac function and heart failure
    Sathyamangla V Naga Prasad
    Department of Medicine, Cell Biology and Genetics, Duke University Medical Center, Durham, NC 27710, USA
    Trends Cardiovasc Med 13:206-12. 2003
    ..This article reviews the role of PI3K in regulating cardiac growth, contractility, beta-adrenergic receptor function, and hypertrophy, as well as possible novel therapeutic strategies in the treatment of heart failure...
  25. pmc Beta-arrestin-mediated beta1-adrenergic receptor transactivation of the EGFR confers cardioprotection
    Takahisa Noma
    Department of Medicine, Duke University Medical Center, Durham, North Carolina 27710, USA
    J Clin Invest 117:2445-58. 2007
    ....
  26. ncbi request reprint Genetic modifier loci affecting survival and cardiac function in murine dilated cardiomyopathy
    Miwako Suzuki
    Department of Medicine and Genetics, Duke University Medical Center, Durham, NC 27710, USA
    Circulation 105:1824-9. 2002
    ..One approach to identify genes that modify disease outcome is to use mouse models that show strong genetic variation of the disease phenotype...
  27. pmc An N-ethyl-N-nitrosourea mutagenesis recessive screen identifies two candidate regions for murine cardiomyopathy that map to chromosomes 1 and 15
    Liliana Fernandez
    Department of Medicine, Duke University Medical Center, DUMC, Durham, NC 27710, USA
    Mamm Genome 20:296-304. 2009
    ..The identification of the genes responsible for the observed phenotype in these families will be strong candidates for disease-causing or disease-modifying genes in patients with heart failure...
  28. pmc Functional selectivity in adrenergic and angiotensin signaling systems
    Chetan B Patel
    Duke University Medical Center, Durham, NC 27710, USA
    Mol Pharmacol 78:983-92. 2010
    ....
  29. pmc Altered blood pressure responses and normal cardiac phenotype in ACE2-null mice
    Susan B Gurley
    Division of Nephrology, Department of Medicine, Duke University and Durham VA Medical Centers, Durham, North Carolina 27705, USA
    J Clin Invest 116:2218-25. 2006
    ..Our data suggest that ACE2 is a functional component of the renin-angiotensin system, metabolizing Ang II and thereby contributing to regulation of blood pressure...
  30. ncbi request reprint Cardiac hypertrophy and altered beta-adrenergic signaling in transgenic mice that express the amino terminus of beta-ARK1
    Janelle R Keys
    Department of Surgery, Duke University Medical Center, Durham, NC 27710, USA
    Am J Physiol Heart Circ Physiol 285:H2201-11. 2003
    ..Thus the amino terminus of beta-ARK1 appears to be critical for normal beta-AR regulation in vivo, which further supports the hypothesis that beta-ARK1 plays a key role in normal and compromised cardiac GPCR signaling...
  31. ncbi request reprint Cardiac hypertrophy: role of G protein-coupled receptors
    Giovanni Esposito
    Department of Medicine, Duke University Medical Center, Durham, North Carolina 27710, USA
    J Card Fail 8:S409-14. 2002
    ....
  32. ncbi request reprint Methods for the detection of altered beta-adrenergic receptor signaling pathways in hypertrophied hearts
    Matthew J Wolf
    Department of Medicine, Duke University Medical Center, Durham, NC, USA
    Methods Mol Med 112:353-62. 2005
    ....
  33. pmc Beta-arrestin-mediated signaling in the heart
    Priyesh A Patel
    School of Medicine, Duke University, Durham, NC, USA
    Circ J 72:1725-9. 2008
    ....
  34. ncbi request reprint Multiple quantitative trait loci modify the heart failure phenotype in murine cardiomyopathy
    Philippe Le Corvoisier
    Department of Medicine, Duke University Medical Center, Durham, NC 27710, USA
    Hum Mol Genet 12:3097-107. 2003
    ..The identification of these novel modifier genes will serve as strong candidates for the discovery of modifiers in human heart failure...
  35. doi request reprint Physiologic and cardiac roles of beta-arrestins
    Priyesh A Patel
    Duke University School of Medicine, Durham, North Carolina 27710, USA
    J Mol Cell Cardiol 46:300-8. 2009
    ..Identifying novel ligands for GPCRs that can block G protein-mediated signaling while simultaneously promoting beta-arrestin-mediated signaling could provide powerful new therapies for cardiac disease...
  36. ncbi request reprint cTnT1, a cardiac troponin T isoform, decreases myofilament tension and affects the left ventricular pressure waveform
    Rashid Nassar
    Department of Pediatrics, Duke University, Durham, NC, USA
    Am J Physiol Heart Circ Physiol 288:H1147-56. 2005
    ....
  37. ncbi request reprint Role for thromboxane receptors in angiotensin-II-induced hypertension
    Helene Francois
    Division of Nephrology, Department of Medicine, Duke University, and Durham VA Medical Centers, Durham, NC 27705, USA
    Hypertension 43:364-9. 2004
    ..However, irrespective of genetic background, the TP receptor makes a robust contribution to the pathogenesis of angiotensin II-dependent hypertension...
  38. ncbi request reprint Left ventricular functional assessment in mice: feasibility of high spatial and temporal resolution ECG-gated blood pool SPECT
    Bennett B Chin
    Department of Radiology, Duke University School of Medicine, Durham, NC 27710, USA
    Radiology 245:440-8. 2007
    ..To prospectively determine feasibility of evaluating murine left ventricular (LV) function with electrocardiographically (ECG)-gated blood pool single photon emission computed tomography (SPECT)...
  39. pmc Cardiac GPCRs: GPCR signaling in healthy and failing hearts
    Natasha C Salazar
    Department of Medicine, Duke University Medical Center, Durham, NC 27710, USA
    Biochim Biophys Acta 1768:1006-18. 2007
    ..The focus of this review is to highlight the most commonly studied and clinically targeted cardiac GPCRs, placing emphasis on their common signaling components implicated in cardiac disease...
  40. ncbi request reprint Regulation of beta-adrenergic receptor signaling by S-nitrosylation of G-protein-coupled receptor kinase 2
    Erin J Whalen
    Department of Medicine, Duke University Medical Center, Durham, NC 27710, USA
    Cell 129:511-22. 2007
    ..Cys340 of GRK2 is identified as a principal locus of inhibition by S-nitrosylation. Our studies thus reveal a central molecular mechanism through which GPCR signaling is regulated...
  41. pmc beta-Arrestin-biased agonism of the angiotensin receptor induced by mechanical stress
    Kriti Rakesh
    Department of Medicine, Duke University Medical Center, DUMC 3104, 226 CARL Building, Durham, NC 27710, USA
    Sci Signal 3:ra46. 2010
    ..These data show that the heart responds to acute increases in mechanical stress by activating beta-arrestin-mediated cell survival signals...
  42. pmc Endogenous S-nitrosothiols protect against myocardial injury
    Brian Lima
    Department of Surgery, Duke University Medical Center, Durham, NC 27710, USA
    Proc Natl Acad Sci U S A 106:6297-302. 2009
    ..These results suggest innovative approaches to modulate angiogenesis and preserve cardiac function...
  43. pmc Cardiac copper deficiency activates a systemic signaling mechanism that communicates with the copper acquisition and storage organs
    Byung Eun Kim
    Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, NC 27710, USA
    Cell Metab 11:353-63. 2010
    ..These studies identify ATP7A as a candidate for hepatic Cu mobilization in response to peripheral tissue demand, and illuminate a systemic regulation in which the Cu status of the heart is signaled to organs that take up and store Cu...
  44. pmc Gene deletion screen for cardiomyopathy in adult Drosophila identifies a new notch ligand
    Il Man Kim
    Department of Medicine, Duke University Medical Center, Durham, NC 27710, USA
    Circ Res 106:1233-43. 2010
    ..Drosophila has been recognized as a model to study human cardiac diseases...
  45. pmc Cardiovascular phenotyping of the mouse heart using a 4D radial acquisition and liposomal Gd-DTPA-BMA
    Elizabeth Bucholz
    Center for In Vivo Microscopy, Duke University, Durham, North Carolina, USA
    Magn Reson Med 63:979-87. 2010
    ..This study shows that MRI is capable of efficient, high-throughput, four-dimensional cardiovascular phenotyping of the mouse...
  46. pmc Beta-arrestin2-mediated inotropic effects of the angiotensin II type 1A receptor in isolated cardiac myocytes
    Keshava Rajagopal
    Department of Surgery, Howard Hughes Medical Institute, Duke University Medical Center, Durham, NC 27710, USA
    Proc Natl Acad Sci U S A 103:16284-9. 2006
    ..Such ligands may have potential as a novel class of therapeutic agents...
  47. ncbi request reprint Dual inhibition of beta-adrenergic and angiotensin II receptors by a single antagonist: a functional role for receptor-receptor interaction in vivo
    Liza Barki-Harrington
    Department of Medicine, Duke University Medical Center, Durham, NC, 27710, USA
    Circulation 108:1611-8. 2003
    ..Although the renin-angiotensin and the beta-adrenergic systems are interrelated, a direct interaction between beta-adrenergic receptors (betaARs) and angiotensin II type 1 receptors (AT1Rs) has not been identified...
  48. ncbi request reprint Vascular-targeted overexpression of G protein-coupled receptor kinase-2 in transgenic mice attenuates beta-adrenergic receptor signaling and increases resting blood pressure
    Andrea D Eckhart
    Department of Surgery, Duke University Medical Center, Durham, North Carolina 27710, USA
    Mol Pharmacol 61:749-58. 2002
    ..Moreover, they suggest that GRK2 plays an important role in vascular control and may represent a novel therapeutic target for hypertension...
  49. ncbi request reprint Competitive displacement of phosphoinositide 3-kinase from beta-adrenergic receptor kinase-1 improves postinfarction adverse myocardial remodeling
    Antonio Curcio
    Dept of Medicine, Cell Biology, and Molecular Genetics, Duke Univ Medical Center, DUMC 3104, Durham, NC 27710, USA
    Am J Physiol Heart Circ Physiol 291:H1754-60. 2006
    ..Together, these results demonstrate that adverse remodeling of the ventricle after MI can be attenuated by a strategy that prevents recruitment of PI3K to the plasma membrane and restores normal beta-AR function...
  50. ncbi request reprint Protein kinase activity of phosphoinositide 3-kinase regulates beta-adrenergic receptor endocytosis
    Sathyamangla V Naga Prasad
    Division of Cardiology, Department of Medicine, Duke University Medical Center, Durham, NC 27710, USA
    Nat Cell Biol 7:785-96. 2005
    ..These studies demonstrate a previously unknown role for the protein phosphorylation activity of PI(3)K in betaAR internalization and identify non-muscle tropomyosin as a cellular substrate for protein kinase activity of PI(3)K...
  51. ncbi request reprint Targeted inhibition of beta-adrenergic receptor kinase-1-associated phosphoinositide-3 kinase activity preserves beta-adrenergic receptor signaling and prolongs survival in heart failure induced by calsequestrin overexpression
    Cinzia Perrino
    Department of Medicine, Duke University Medical Center, Durham, North Carolina, USA
    J Am Coll Cardiol 45:1862-70. 2005
    ..Desensitization and down-regulation of beta-adrenergic receptors (betaARs) are prominent features of heart failure largely mediated by increased levels of betaAR kinase-1 (betaARK1)...
  52. ncbi request reprint Protein kinase A and G protein-coupled receptor kinase phosphorylation mediates beta-1 adrenergic receptor endocytosis through different pathways
    Antonio Rapacciuolo
    Department of Medicine and Cell Biology, Medical Center, Duke University, Durham, North Carolina 27710, USA
    J Biol Chem 278:35403-11. 2003
    ..e. PKA-mediated phosphorylation directs internalization via a caveolae pathway, whereas GRK-mediated phosphorylation directs it through clathrin-coated pits...
  53. pmc An essential role for mitochondrial aldehyde dehydrogenase in nitroglycerin bioactivation
    Zhiqiang Chen
    Department of Medicine and Howard Hughes Medical Institute, Duke University Medical Center, Durham, NC 27710, USA
    Proc Natl Acad Sci U S A 102:12159-64. 2005
    ....
  54. pmc High oxygen prevents fetal lethality due to lack of catecholamines
    Margie A Ream
    Dept of Neurobiology, Box 3209, Duke Univ Medical Center, Durham, NC 27710, USA
    Am J Physiol Regul Integr Comp Physiol 295:R942-53. 2008
    ..We suggest that norepinephrine mediates fetal survival by maintaining oxygen homeostasis...
  55. pmc beta-Arrestin mediates beta1-adrenergic receptor-epidermal growth factor receptor interaction and downstream signaling
    Douglas G Tilley
    Department of Medicine, Duke University, Medical Center, Durham, North Carolina 27710, USA
    J Biol Chem 284:20375-86. 2009
    ..These data reveal a new signaling paradigm in which beta-arrestin is required for the maintenance of a beta1AR-EGFR interaction that can direct cytosolic targeting of ERK in response to catecholamine stimulation...
  56. ncbi request reprint Restoration of beta-adrenergic receptor signaling and contractile function in heart failure by disruption of the betaARK1/phosphoinositide 3-kinase complex
    Cinzia Perrino
    Department of Medicine, Cell Biology and Molecular Genetics, Duke University Medical Center, Durham, NC 27710, USA
    Circulation 111:2579-87. 2005
    ..We tested the hypothesis that inhibition of receptor-targeted PI3K activity would alter receptor trafficking and ameliorate betaAR signaling, ultimately improving contractility of failing cardiomyocytes...
  57. ncbi request reprint Selective inhibition of heterotrimeric Gs signaling. Targeting the receptor-G protein interface using a peptide minigene encoding the Galpha(s) carboxyl terminus
    David S Feldman
    Department of Medicine, Duke University Medical Center, Durham, North Carolina 27710, USA
    J Biol Chem 277:28631-40. 2002
    ..ERK activation by the G(q/11)-coupled alpha(1B)AR was unaffected by GsCT. These findings suggest that peptide G protein inhibitors can provide insights into the complex interplay between G protein pools in cellular regulation...
  58. ncbi request reprint Estrogen receptor-beta mediates male-female differences in the development of pressure overload hypertrophy
    Maryanne Skavdahl
    Laboratory of Signal Transduction, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA
    Am J Physiol Heart Circ Physiol 288:H469-76. 2005
    ..These data suggest an important role for estrogen receptor-beta in attenuating the hypertrophic response to pressure overload in females...
  59. ncbi request reprint Sensing heart stress
    Liza Barki-Harrington
    Nat Med 9:19-20. 2003
  60. pmc Muscle-specific RING finger 1 is a bona fide ubiquitin ligase that degrades cardiac troponin I
    Vishram Kedar
    Carolina Cardiovascular Biology Center, University of North Carolina, Chapel Hill, NC 27599 7126, USA
    Proc Natl Acad Sci U S A 101:18135-40. 2004
    ..In cardiomyocytes, these processes may determine the balance between hypertrophic and antihypertrophic signals and the regulation of myocyte contractile responses in the setting of heart failure...
  61. ncbi request reprint Regional absence of mitochondria causing energy depletion in the myocardium of muscle LIM protein knockout mice
    Bianca J C van den Bosch
    Cardiovascular Research Institute Maastricht CARIM, Department of Genetics and Cell Biology, Maastricht University, P O Box 616, 6200 MD Maastricht, The Netherlands
    Cardiovasc Res 65:411-8. 2005
    ..We tested the hypothesis that defects in the cytoskeleton lead to dilated cardiomyopathy through mitochondrial dysfunction in the MLP mouse model...
  62. pmc Role of soluble epoxide hydrolase in postischemic recovery of heart contractile function
    John M Seubert
    Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, AB, Canada
    Circ Res 99:442-50. 2006
    ..Together, these data suggest that targeted disruption of sEH increases the availability of cardioprotective EETs that work by activating PI3K signaling pathways and K+ channels...
  63. ncbi request reprint Reduced life span with heart and muscle dysfunction in Drosophila sarcoglycan mutants
    Michael J Allikian
    Department of Medicine, University of Chicago, Chicago, IL 60637, USA
    Hum Mol Genet 16:2933-43. 2007
    ..Together, these data demonstrate the essential nature of the transmembrane and extracellular domains of Drosophila delta-sarcoglycan for normal muscle structure and function...
  64. pmc Ankyrin-B syndrome: enhanced cardiac function balanced by risk of cardiac death and premature senescence
    Peter J Mohler
    Department of Internal Medicine, University of Iowa Carver College of Medicine, Iowa City, Iowa, United States of America
    PLoS ONE 2:e1051. 2007
    ..Together these findings suggest a constellation of traits that we term "ankyrin-B syndrome", which may contribute to both aging-related disorders and enhanced cardiac function...
  65. ncbi request reprint Increased myocardial contractility and enhanced exercise function in transgenic mice overexpressing either adenylyl cyclase 5 or 8
    Giovanni Esposito
    Division of Cardiology, University Federico II of Naples, Via Pansini 5, 80131 Naples, Italy
    Basic Res Cardiol 103:22-30. 2008
    ..Whether AC overexpression affects intrinsic cardiac contractility in an isoform-specific fashion determining a change in exercise capacity is currently unknown...
  66. ncbi request reprint Prostacyclin protects against elevated blood pressure and cardiac fibrosis
    Helene Francois
    Department of Medicine, Duke University and Durham VA Medical Centers, Durham, North Carolina 27705
    Cell Metab 2:201-7. 2005
    ..Our data suggest that adjuvant therapy that blocks unrestrained Tx actions might protect against end-organ damage without affecting blood pressure in patients taking COX-2 inhibitors...
  67. ncbi request reprint Enhanced postischemic functional recovery in CYP2J2 transgenic hearts involves mitochondrial ATP-sensitive K+ channels and p42/p44 MAPK pathway
    John Seubert
    Division of Intramural Research, NIEHS NIH, Research Triangle Park, NC 27709, USA
    Circ Res 95:506-14. 2004
    ..Together, these data suggest that CYP2J2-derived metabolites are cardioprotective after ischemia, and the mechanism for this cardioprotection involves activation of mitoK(ATP) and p42/p44 MAPK...
  68. ncbi request reprint G protein-coupled receptor internalization signaling is required for cardioprotection in ischemic preconditioning
    Haiyan Tong
    Laboratory of Signal Transduction, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC 27709, USA
    Circ Res 94:1133-41. 2004
    ..We found that the catalytically inactive mutant of PI3Kgamma blocks the protection of PC. In summary, these data suggest the novel finding that the cardioprotective effect of PC requires receptor internalization...
  69. ncbi request reprint GATA4 and the two sides of gene expression reprogramming
    Cinzia Perrino
    Circ Res 98:715-6. 2006
  70. ncbi request reprint Transgenic overexpression of the Ca2+-binding protein S100A1 in the heart leads to increased in vivo myocardial contractile performance
    Patrick Most
    Medizinische Universitätsklinik und Poliklinik III, Universität zu Heidelberg, 69115 Heidelberg
    J Biol Chem 278:33809-17. 2003
    ..Because S100A1 protein expression is down-regulated in heart failure, increasing S100A1 expression in the heart may represent a novel means to augment contractility...
  71. pmc Discordant on/off switching of gene expression in myocytes during cardiac hypertrophy in vivo
    Kumar Pandya
    Department of Pathology and Laboratory Medicine, University of North Carolina, Chapel Hill, NC 27599, USA
    Proc Natl Acad Sci U S A 105:13063-8. 2008
    ....
  72. ncbi request reprint Reversal of cardiac remodeling by modulation of adrenergic receptors: a new frontier in heart failure
    Cinzia Perrino
    Division of Cardiology, Department of Clinical Medicine, Cardiovascular and Immunological Sciences, Federico II University, Naples, Italy
    Curr Opin Cardiol 22:443-9. 2007
    ..Heart failure is a common clinical syndrome, and despite intensive medical therapy it remains a leading cause of global morbidity and mortality. Pathological stimuli promote a general remodeling process in the heart...
  73. ncbi request reprint Targeted inhibition of phosphoinositide 3-kinase activity as a novel strategy to normalize beta-adrenergic receptor function in heart failure
    Cinzia Perrino
    Division of Cardiology, University Federico II, Via Pansini 5, Naples, 80131, Italy
    Vascul Pharmacol 45:77-85. 2006
    ..In this review we will discuss the role of betaAR-targeted PI3K activity and novel experimental strategies to disrupt the betaARK1/PI3K complex and in turn ameliorate betaAR dysfunction and the progression of heart failure...
  74. doi request reprint Beta-arrestins: multifunctional cellular mediators
    Liza Barki-Harrington
    Department of Biology, University of Haifa, Israel
    Physiology (Bethesda) 23:17-22. 2008
    ..This review explores the many functions of beta-arrestins, with an emphasis on their recently identified role as regulators of receptor signaling...

Research Grants36

  1. BETA ADRENERGIC RECEPTOR PHOSPHORYLATION--HEART FAILURE
    Howard Rockman; Fiscal Year: 2003
    ..The collaborations with the other R01's should provide a unique opportunity to understand the relationships between betaAR signaling, E-C coupling and myocyte cell survival. ..
  2. MULTIDISCIPLINARY HEART AND VASCULAR DISEASES
    Howard Rockman; Fiscal Year: 2007
    ..End of Abstract) ..
  3. MECHANISMS OF MALADAPTATION IN HEART FAILURE
    Howard Rockman; Fiscal Year: 2003
    ..Calsequestrin overexpressing mice will be mated to transgenic mice overexpressing the constitutively active and catalytic inactive mutants of PI3Kp110gamma followed by a comprehensive analysis of the phenotype. ..
  4. Modifier Genes in Heart Failure
    Howard Rockman; Fiscal Year: 2005
    ..Genetic epidemiology will be performed in collaboration with the Duke Center for Human Genetics. ..
  5. MECHANISMS OF MALADAPTATION IN HEART FAILURE
    Howard Rockman; Fiscal Year: 2009
    ..This proposal builds on those investigations to advance our understanding of the role PAR dysfunction plays in the development of heart failure. ..
  6. Identifying Cardiomyopathy Genes in Mice and Drosophila
    Howard Rockman; Fiscal Year: 2009
    ..Thus, these four integrated aims will harness the power of mouse and Drosophila genetics to identify and evaluate novel candidate genes for their role in cardiomyopathy. ..
  7. Identifying Cardiomyopathy Genes in Mice and Drosophila
    Howard Rockman; Fiscal Year: 2007
    ..Thus, these four integrated aims will harness the power of mouse and Drosophila genetics to identify and evaluate novel candidate genes for their role in cardiomyopathy. ..
  8. PHENOTYPIC SCREENS FOR CARDIOVASCULAR MUTATIONS IN MICE
    Howard Rockman; Fiscal Year: 2003
    ..4) To develop a high throughput method for detecting plasma peptide hormones and to refine in a high throughput mode, the surrogate marker assays used in specific aims #1, 2, and 3. (End of Abstract.) ..
  9. MECHANISMS OF MALADAPTATION IN HEART FAILURE
    Howard A Rockman; Fiscal Year: 2010
    ..This proposal builds on those investigations to advance our understanding of the role PAR dysfunction plays in the development of heart failure. ..
  10. MECHANISMS OF MALADAPTATION IN HEART FAILURE
    Howard Rockman; Fiscal Year: 2007
    ..This proposal builds on those investigations to advance our understanding of the role ?AR dysfunction plays in the development of heart failure. ..
  11. Genes That Regulate Target Organ Damage in Hypertension
    Howard Rockman; Fiscal Year: 2004
    ..Our long-term goal is to identify genes that confer susceptibility to heart and kidney injury in hypertension. ..
  12. Identifying Cardiomyopathy Genes in Mice and Drosophila
    Howard A Rockman; Fiscal Year: 2010
    ..Simpler model systems, such as Drosophila, provide the unique ability to perform genetic screens to identify genetic modifiers of the Calcineurin pathway that otherwise would be very difficult to do in mammalian systems. ..