Signaling Processes Underlying Cardiovascular Function

Summary

Principal Investigator: Jeffrey Robbins
Abstract: DESCRIPTION (provided by applicant): The central objective of our Program Project Grant "Signaling Processes Underlying Cardiovascular Function," is to extend our investigation of integrating specific signaling pathways underlying cardiac function to normal and pathogenic fibrosis. The central hypothesis is that the signaling pathways centered in the fibroblast are critical to the fibrotic processes characteristic of so much cardiovascular disease and heart failure. There is truly a remarkable lack of data and understanding as to if and how fibroblasts themselves contribute to cardiac disease. The 3 Projects will direct their efforts at determining the exact identity of the signaling pathways within fibroblasts that mediate myofibroblast transformation and longstanding fibrosis in surgically, pharmacologically- and genetically-induced cardiac disease. All of the Projects will also attempt to identify therapeutic windows for impacting favorably on the processes'pathogenic consequences. Our group consists of 3 Project Leaders and 4 Core-oriented investigators who have a track record of sustained and productive collaboration. The synergy and collaborations that underlie the PPG are underscored by the commonality of approach and the seamless use of models across the Projects. The goal of this Program is to prove proof-of-concept of fibroblast-based signaling pathways'importance in cardiac disease. Project 1's title is: Fibrotic signaling in cardiomyopathy. Jeffrey Robbins, Ph.D., Professor of Pediatrics, will focus on testing the central hypothesis that TGF[unreadable] signaling processes that are fibroblast-based play a critical role in the fibrotic response in sarcomere-based and nonsarcomere- based disease. Project 2's title is: Wnt/[unreadable]-catenin signaling and cardiac fibrosis. Katherine Yutzey, Ph.D., Professor of Pediatrics, will test the hypothesis that Wnt/[unreadable]-catenin signaling promotes normal development of interstitial fibroblasts and also contributes to pathologic interstitial fibrosis in adult cardiovascular disease. Project 3's title s: TGF[unreadable] signaling and its role in cardiac fibrosis. Jeffery Molkentin, PhD., Professor of Pediatrics, will focus on canonical and non-canonical TGF[unreadable] signaling in the cardiac fibroblast during cardiac disease development induced as a result of surgical intervention. The hypothesis is that the fibroblast responds to TGF[unreadable] and other cytokines through select signaling pathways in promoting fibrosis and maladaptive remodeling. These projects are supported by 3 Cores: Core A: The Administrative Core;Core B: The Physiology Core and Core C: The Imaging-Cell Culture Core. (End of Abstract)
Funding Period: 2002-06-06 - 2018-05-31
more information: NIH RePORT

Top Publications

  1. pmc Myosin-binding protein C displaces tropomyosin to activate cardiac thin filaments and governs their speed by an independent mechanism
    Ji Young Mun
    Department of Cell and Developmental Biology, University of Massachusetts Medical School, Worcester, MA 01655
    Proc Natl Acad Sci U S A 111:2170-5. 2014
  2. pmc Electron microscopy and 3D reconstruction of F-actin decorated with cardiac myosin-binding protein C (cMyBP-C)
    Ji Young Mun
    Department of Cell Biology, University of Massachusetts Medical School, 55 Lake Avenue North, Worcester, MA 01655, USA
    J Mol Biol 410:214-25. 2011
  3. pmc A critical function for Ser-282 in cardiac Myosin binding protein-C phosphorylation and cardiac function
    Sakthivel Sadayappan
    Department of Cell and Molecular Physiology, Stritch School of Medicine, Loyola University Chicago, IL, USA
    Circ Res 109:141-50. 2011
  4. pmc Altered myofilament stoichiometry in response to heart failure in a cardioprotective α-myosin heavy chain transgenic rabbit model
    Brian A Stanley
    Department of Medicine, Division of Cardiology, Johns Hopkins University, Baltimore, MD, USA
    Proteomics Clin Appl 5:147-58. 2011
  5. pmc Signaling and myosin-binding protein C
    Jeanne James
    Department of Pediatrics and the Heart Institute, Cincinnati Children s Hospital Medical Center, Cincinnati, Ohio 45229, USA
    J Biol Chem 286:9913-9. 2011
  6. pmc FoxO transcription factors promote cardiomyocyte survival upon induction of oxidative stress
    Arunima Sengupta
    Heart Institute, Division of Molecular Cardiovascular Biology, Cincinnati Children s Medical Center, Cincinnati, Ohio 45229, USA
    J Biol Chem 286:7468-78. 2011
  7. pmc The transcription factor GATA-6 regulates pathological cardiac hypertrophy
    Jop H van Berlo
    Howard Hughes Medical Institute, Cincinnati Children s Hospital Medical Center, 240 Albert Sabin Way, Cincinnati, OH 45229 3039, USA
    Circ Res 107:1032-40. 2010
  8. pmc Manipulation of death pathways in desmin-related cardiomyopathy
    Alina Maloyan
    Molecular Cardiovascular Biology, Heart Institute, Cincinnati Children s Hospital, Cincinnati, Ohio, USA
    Circ Res 106:1524-32. 2010
  9. pmc Genetic deletion of myostatin from the heart prevents skeletal muscle atrophy in heart failure
    Joerg Heineke
    Department of Pediatrics, University of Cincinnati, Cincinnati Children s Hospital Medical Center, Cincinnati, USA
    Circulation 121:419-25. 2010
  10. pmc Cardiac stem cell genetic engineering using the alphaMHC promoter
    Brandi Bailey
    San Diego State University, SDSU Heart Institute, Department of Biology, San Diego, CA 92182, USA
    Regen Med 4:823-33. 2009

Research Grants

  1. CARDIOVASCULAR DYNAMICS AND THEIR CONTROL
    John E Hall; Fiscal Year: 2013

Detail Information

Publications62

  1. pmc Myosin-binding protein C displaces tropomyosin to activate cardiac thin filaments and governs their speed by an independent mechanism
    Ji Young Mun
    Department of Cell and Developmental Biology, University of Massachusetts Medical School, Worcester, MA 01655
    Proc Natl Acad Sci U S A 111:2170-5. 2014
    ..These results suggest that cMyBP-C may both modulate thin filament activity, by physically displacing tropomyosin from its low Ca(2+) position on actin, and govern contractile speed by an independent molecular mechanism. ..
  2. pmc Electron microscopy and 3D reconstruction of F-actin decorated with cardiac myosin-binding protein C (cMyBP-C)
    Ji Young Mun
    Department of Cell Biology, University of Massachusetts Medical School, 55 Lake Avenue North, Worcester, MA 01655, USA
    J Mol Biol 410:214-25. 2011
    ..The location of binding was such that it could modulate tropomyosin position and would interfere with myosin head binding to actin...
  3. pmc A critical function for Ser-282 in cardiac Myosin binding protein-C phosphorylation and cardiac function
    Sakthivel Sadayappan
    Department of Cell and Molecular Physiology, Stritch School of Medicine, Loyola University Chicago, IL, USA
    Circ Res 109:141-50. 2011
    ..In vitro and in vivo experiments suggest the nonequivalence of these sites and the potential importance of Ser-282 phosphorylation in modulating the protein's overall phosphorylation and myocardial function...
  4. pmc Altered myofilament stoichiometry in response to heart failure in a cardioprotective α-myosin heavy chain transgenic rabbit model
    Brian A Stanley
    Department of Medicine, Division of Cardiology, Johns Hopkins University, Baltimore, MD, USA
    Proteomics Clin Appl 5:147-58. 2011
    ..Hypothesizing that MHC isoform content alterations would impact sarcomere and mitochondrial energetics protein complement, we investigated the impact of α-MHC overexpression on global cardiac protein expression...
  5. pmc Signaling and myosin-binding protein C
    Jeanne James
    Department of Pediatrics and the Heart Institute, Cincinnati Children s Hospital Medical Center, Cincinnati, Ohio 45229, USA
    J Biol Chem 286:9913-9. 2011
    ..Thus, cMyBP-C is a critical nodal point that has both important structural and signaling roles and whose modifications are known to cause significant human cardiac disease...
  6. pmc FoxO transcription factors promote cardiomyocyte survival upon induction of oxidative stress
    Arunima Sengupta
    Heart Institute, Division of Molecular Cardiovascular Biology, Cincinnati Children s Medical Center, Cincinnati, Ohio 45229, USA
    J Biol Chem 286:7468-78. 2011
    ..These data support a critical role for FoxOs in promoting cardiomyocyte survival during conditions of oxidative stress through induction of antioxidants and cell survival pathways...
  7. pmc The transcription factor GATA-6 regulates pathological cardiac hypertrophy
    Jop H van Berlo
    Howard Hughes Medical Institute, Cincinnati Children s Hospital Medical Center, 240 Albert Sabin Way, Cincinnati, OH 45229 3039, USA
    Circ Res 107:1032-40. 2010
    ..The highly related transcription factor GATA-6 is also expressed in the adult heart, although its role in controlling the hypertrophic program is unknown...
  8. pmc Manipulation of death pathways in desmin-related cardiomyopathy
    Alina Maloyan
    Molecular Cardiovascular Biology, Heart Institute, Cincinnati Children s Hospital, Cincinnati, Ohio, USA
    Circ Res 106:1524-32. 2010
    ..However, the role of mitochondrial dysfunction and apoptosis in the overall course of the disease was unclear...
  9. pmc Genetic deletion of myostatin from the heart prevents skeletal muscle atrophy in heart failure
    Joerg Heineke
    Department of Pediatrics, University of Cincinnati, Cincinnati Children s Hospital Medical Center, Cincinnati, USA
    Circulation 121:419-25. 2010
    ..Myostatin is a cytokine of the transforming growth factor-beta superfamily that is known to control muscle wasting...
  10. pmc Cardiac stem cell genetic engineering using the alphaMHC promoter
    Brandi Bailey
    San Diego State University, SDSU Heart Institute, Department of Biology, San Diego, CA 92182, USA
    Regen Med 4:823-33. 2009
    ..The early increased expression of survival kinases augments expansion of the cardiogenic CSC pool and subsequent daughter progeny...
  11. pmc Enhancement of myocardial regeneration through genetic engineering of cardiac progenitor cells expressing Pim-1 kinase
    Kimberlee M Fischer
    San Diego State Heart Institute, San Diego State University, San Diego, CA, USA
    Circulation 120:2077-87. 2009
    ....
  12. pmc Effects of myosin heavy chain manipulation in experimental heart failure
    Jeanne James
    The Heart Institute, Cincinnati Children s Hospital Medical Center and the University of Cincinnati School of Medicine, 241 Albert Sabin Way MLC 7020, Cincinnati, OH 45229 3039, USA
    J Mol Cell Cardiol 48:999-1006. 2010
    ..Future considerations of myosin isoform manipulation as a therapeutic strategy should consider the underlying etiology of cardiac dysfunction...
  13. pmc ASK1 regulates cardiomyocyte death but not hypertrophy in transgenic mice
    Qinghang Liu
    Department of Pediatrics, Division of Molecular Cardiovascular Biology, University of Cincinnati, Cincinnati Children s Hospital Medical Center, Cincinnati, OH 45229 3039, USA
    Circ Res 105:1110-7. 2009
    ..Apoptosis signal-regulating kinase (ASK)1 is a central upstream kinase in the greater mitogen-activated protein kinase cascade that mediates growth and death decisions in cardiac myocytes in response to diverse pathological stimuli...
  14. pmc Effects of cardiac myosin isoform variation on myofilament function and crossbridge kinetics in transgenic rabbits
    Takeki Suzuki
    Department of Medicine, Cardiology Unit, Fletcher Allen Health Care, Burlington, VT 05401, USA
    Circ Heart Fail 2:334-41. 2009
    ..This study was undertaken to identify a myofilament-based mechanism underlying tachycardia-induced cardiomyopathy protection and to extrapolate the impact of MHC isoform variation on myofilament function in human hearts...
  15. pmc Atg7 induces basal autophagy and rescues autophagic deficiency in CryABR120G cardiomyocytes
    J Scott Pattison
    Department of Pediatrics, Division of Molecular Cardiovascular Biology, Cincinnati Children s Hospital Medical Center, Cincinnati, OH 45229 3039, USA
    Circ Res 109:151-60. 2011
    ..Impaired autophagic function is a potential cause of misfolded protein accumulations, cytoplasmic aggregate loads, and cardiac disease. Atg7, a mediator of autophagosomal biogenesis, is a putative regulator of autophagic function...
  16. pmc In vivo delivery of nucleic acids via glycopolymer vehicles affords therapeutic infarct size reduction in vivo
    Michael Tranter
    Department of Pharmacology, University of Cincinnati, Cincinnati, Ohio 45267, USA
    Mol Ther 20:601-8. 2012
    ..Additionally, the low toxicity, biodegradation, and outstanding delivery efficacy suggest that these nanomedicines may be clinically applicable for gene regulatory therapy...
  17. ncbi FoxO1 is required in endothelial but not myocardial cell lineages during cardiovascular development
    Arunima Sengupta
    Division of Molecular Cardiovascular Biology, Cincinnati Children s Hospital, Cincinnati, Ohio, USA
    Dev Dyn 241:803-13. 2012
    ..5 with severe cardiovascular defects; however, the cell-type-specific requirements for FoxO1 in cardiovascular development are unknown. Here we examine the role of FoxO1 using a conditional loss of function approach...
  18. pmc Proteotoxicity: an underappreciated pathology in cardiac disease
    Marco Sandri
    Venetian Institute of Molecular Medicine VIMM, Padova, Italy Consiglio Nazionale delle Ricerche CNR Institute of Neuroscience, Padova, Italy Department of Biomedical Sciences, University of Padova, Padova, Italy
    J Mol Cell Cardiol 71:3-10. 2014
    ..This article is part of a Special Issue entitled "Protein Quality Control, the Ubiquitin Proteasome System, and Autophagy." ..
  19. pmc Proteasomal and lysosomal protein degradation and heart disease
    Xuejun Wang
    Division of Basic Biomedical Sciences, Sanford School of Medicine of the University of South Dakota, Vermillion, SD 57069, USA Electronic address
    J Mol Cell Cardiol 71:16-24. 2014
    ..This article is part of a Special Issue entitled "Protein Quality Control, the Ubiquitin Proteasome System, and Autophagy". ..
  20. pmc Post-translational control of cardiac hemodynamics through myosin binding protein C
    Manish K Gupta
    The Heart Institute, Department of Pediatrics, The Cincinnati Children s Hospital Medical Center, Cincinnati, OH, 45229, USA
    Pflugers Arch 466:231-6. 2014
    ..Phosphorylation of the M domain can regulate the manner in which actin and myosin interact, affecting the cross bridge cycle and ultimately, cardiac hemodynamics. ..
  21. pmc Differential expression of embryonic epicardial progenitor markers and localization of cardiac fibrosis in adult ischemic injury and hypertensive heart disease
    Caitlin M Braitsch
    The Heart Institute, Division of Molecular Cardiovascular Biology, Cincinnati Children s Hospital Medical Center, 240 Albert Sabin Way, ML 7020, Cincinnati, OH 45229, USA
    J Mol Cell Cardiol 65:108-19. 2013
    ..Together, these data provide evidence for distinct fibrogenic mechanisms that include Tcf21, separate from Wt1 and Tbx18, in different fibroblast populations in response to specific types of cardiac injury. ..
  22. pmc Functional dissection of myosin binding protein C phosphorylation
    Manish K Gupta
    The Heart Institute, Department of Pediatrics, Cincinnati Children s Hospital Medical Center, Cincinnati, OH 45229, USA
    J Mol Cell Cardiol 64:39-50. 2013
    ..The new DAA and AAD constructs show that phosphorylation at one site in the absence of the ability to phosphorylate the other sites, depending upon the particular residues involved, can lead to severe cardiac remodeling and dysfunction. ..
  23. pmc An endogenously produced fragment of cardiac myosin-binding protein C is pathogenic and can lead to heart failure
    Md Abdur Razzaque
    Department of Pediatrics, The Heart Institute, The Cincinnati Children s Hospital Medical Center, Cincinnati, OH 45229, USA
    Circ Res 113:553-61. 2013
    ..Elevated levels of the fragment can be detected in the diseased mouse and human heart, but its ability to interfere with normal cardiac function in the intact animal is unexplored...
  24. ncbi Tbx20 promotes cardiomyocyte proliferation and persistence of fetal characteristics in adult mouse hearts
    Santanu Chakraborty
    Department of Biology, Presidency University, Kolkata 700073, India
    J Mol Cell Cardiol 62:203-13. 2013
    ..Thus, Tbx20 overexpression beginning in the fetal period activates multiple cardiac proliferative pathways after birth and maintains adult cardiomyocytes in an immature state in vivo. ..
  25. pmc FoxO1 and FoxM1 transcription factors have antagonistic functions in neonatal cardiomyocyte cell-cycle withdrawal and IGF1 gene regulation
    Arunima Sengupta
    The Heart Institute, Division of Molecular Cardiovascular Biology, Cincinnati Children s Medical Center, Cincinnati, OH 45229, USA
    Circ Res 112:267-77. 2013
    ..In the mammalian heart, cardiomyocytes withdraw from the cell cycle and initiate hypertrophic growth soon after birth, but the transcriptional regulatory mechanisms that control these neonatal transitions are not well-defined...
  26. pmc Determination of the critical residues responsible for cardiac myosin binding protein C's interactions
    Md Shenuarin Bhuiyan
    J Mol Cell Cardiol 53:838-47. 2012
    ....
  27. pmc Lost in transgenesis: a user's guide for genetically manipulating the mouse in cardiac research
    Jennifer Davis
    Department of Pediatrics, University of Cincinnati, Howard Hughes Medical Institute, Cincinnati Children s Hospital Medical Center, 240 Albert Sabin Way, S4 409, Cincinnati, OH 45229, USA
    Circ Res 111:761-77. 2012
    ..This review uses examples from the field to illustrate the vast spectrum of experimental and design details that must be considered when using genetically modified mouse models to study cardiac biology...
  28. pmc Pod1/Tcf21 is regulated by retinoic acid signaling and inhibits differentiation of epicardium-derived cells into smooth muscle in the developing heart
    Caitlin M Braitsch
    Division of Molecular Cardiovascular Biology, Cincinnati Children s Hospital Medical Center, ML 7020, 240 Albert Sabin Way, Cincinnati, OH 45229, USA
    Dev Biol 368:345-57. 2012
    ..Together, these data demonstrate a critical role for Pod1 in controlling mesenchymal progenitor cell differentiation into SM and fibroblast lineages during cardiac development...
  29. pmc FoxO transcription factors promote autophagy in cardiomyocytes
    Arunima Sengupta
    Division of Molecular Cardiovascular Biology, Cincinnati Children s Medical Center, Cincinnati, Ohio 45229, USA
    J Biol Chem 284:28319-31. 2009
    ..Together these results provide evidence for an important role for FoxO1 and FoxO3 in regulating autophagy and cell size in cardiomyocytes...
  30. pmc Protein kinase C{alpha}, but not PKC{beta} or PKC{gamma}, regulates contractility and heart failure susceptibility: implications for ruboxistaurin as a novel therapeutic approach
    Qinghang Liu
    Children s Hospital Medical Center, Division of Molecular Cardiovascular Biology, 3333 Burnet Ave, University of Cincinnati, Cincinnati, OH 45229 3039, USA
    Circ Res 105:194-200. 2009
    ....
  31. pmc Inhibition of ischemic cardiomyocyte apoptosis through targeted ablation of Bnip3 restrains postinfarction remodeling in mice
    Abhinav Diwan
    Center for Molecular Cardiovascular Research and Department of Pediatrics, University of Cincinnati, Cincinnati, Ohio, USA
    J Clin Invest 117:2825-33. 2007
    ..These studies identify postischemic apoptosis by myocardial Bnip3 as a major determinant of ventricular remodeling in the infarcted heart, suggesting that Bnip3 may be an attractive therapeutic target...
  32. pmc Phospholamban overexpression in transgenic rabbits
    JAMES SCOTT PATTISON
    Division of Molecular Cardiovascular Biology, Cincinnati Children s Hospital Research Foundation, 3333 Burnet Avenue, Cincinnati, OH 45229 3039, USA
    Transgenic Res 17:157-70. 2008
    ..Exceeding a relatively narrow window of phospholamban expression results in significant morbidity and early death...
  33. pmc Genetic manipulation of periostin expression reveals a role in cardiac hypertrophy and ventricular remodeling
    Toru Oka
    Department of Pediatrics, University of Cincinnati, Division of Molecular Cardiovascular Biology, Children s Hospital Medical Center, Cincinnati, OH 45229 3039, USA
    Circ Res 101:313-21. 2007
    ..These are the first genetic data detailing the function of Pn in the adult heart as a regulator of cardiac remodeling and hypertrophy...
  34. pmc Unrestrained erythroblast development in Nix-/- mice reveals a mechanism for apoptotic modulation of erythropoiesis
    Abhinav Diwan
    Center for Molecular Cardiovascular Research and Department of Pediatrics, Children s Hospital Medical Center, University of Cincinnati, Cincinnati, OH 45267, USA
    Proc Natl Acad Sci U S A 104:6794-9. 2007
    ..These results suggest that physiological codependence and coordinated regulation of pro- and antiapoptotic Bcl2 family members may represent a general regulatory paradigm in hematopoiesis...
  35. pmc Voltage-dependent anion channels are dispensable for mitochondrial-dependent cell death
    Christopher P Baines
    Department of Pediatrics, University of Cincinnati, Cincinnati Children s Hospital Medical Center, Cincinnati, OH 45229, USA
    Nat Cell Biol 9:550-5. 2007
    ..These results indicate that Vdacs are dispensable for both MPT and Bcl-2 family member-driven cell death...
  36. ncbi Cardiomyocyte degeneration with calpain deficiency reveals a critical role in protein homeostasis
    Anita S Galvez
    Center for Molecular Cardiovascular Research, University of Cincinnati, OH, USA
    Circ Res 100:1071-8. 2007
    ....
  37. pmc Genetic disruption of calcineurin improves skeletal muscle pathology and cardiac disease in a mouse model of limb-girdle muscular dystrophy
    Stephanie A Parsons
    Department of Pediatrics, University of Cincinnati, Cincinnati Children s Hospital Medical Center, Cincinnati, Ohio 45229 3039, USA
    J Biol Chem 282:10068-78. 2007
    ..Our results suggest that inhibition of Cn may benefit select types of muscular dystrophy...
  38. ncbi Developmental regulation of the mouse IGF-I exon 1 promoter region by calcineurin activation of NFAT in skeletal muscle
    Christina M Alfieri
    Division of Molecular Cardiovascular Biology, Cincinnati Children s Medical Center, ML 7020, 3333 Burnet Ave, Cincinnati, OH 45229, USA
    Am J Physiol Cell Physiol 292:C1887-94. 2007
    ..The identification of a calcineurin/NFAT-responsive element in the IGF-I gene represents a potential mechanism of intersection of these signaling pathways in the control of muscle development and homeostasis...
  39. ncbi Heart failure and protein quality control
    Xuejun Wang
    Division of Basic Biomedical Sciences, Sanford School of Medicine of the University of South Dakota, Vermillion, SD, USA
    Circ Res 99:1315-28. 2006
    ..Here, we examine recent data pointing to the importance of protein quality control in cardiac homeostasis and disease...
  40. ncbi Cardiac-specific ablation of G-protein receptor kinase 2 redefines its roles in heart development and beta-adrenergic signaling
    Scot J Matkovich
    Center for Molecular Cardiovascular Research, University of Cincinnati, Ohio, USA
    Circ Res 99:996-1003. 2006
    ..In the adult heart, cardiac GRK2 is a major factor regulating inotropic and lusitropic tachyphylaxis to beta-adrenergic agonist, which likely contributes to its protective effects in catecholamine cardiomyopathy...
  41. ncbi Containing hypertrophy with a PICOT fence
    Gerald W Dorn
    Circ Res 99:228-30. 2006
  42. pmc Pharmacological- and gene therapy-based inhibition of protein kinase Calpha/beta enhances cardiac contractility and attenuates heart failure
    Michael Hambleton
    Department of Pediatrics, University of Cincinnati, Cincinnati Children s Hospital Medical Center, Cincinnati, Ohio 45229 3039, USA
    Circulation 114:574-82. 2006
    ....
  43. pmc Calcineurin-dependent cardiomyopathy is activated by TRPC in the adult mouse heart
    Hiroyuki Nakayama
    Department of Pediatrics, University of Cincinnati, Children s Hospital Medical Center, Cincinnati, Ohio, USA
    FASEB J 20:1660-70. 2006
    ..Thus, enhanced store-operated Ca2+ entry in the heart can regulate calcineurin-NFAT signaling in vivo, which could secondarily impact the hypertrophic response and cardiomyopathy...
  44. pmc Inducible and myocyte-specific inhibition of PKCalpha enhances cardiac contractility and protects against infarction-induced heart failure
    Michael Hambleton
    Division of Molecular Cardiovascular Biology, Department of Pediatrics, Cincinnati Children s Hospital Medical Center, 3333 Burnet Avenue, Cincinnati, OH 45229 3039, USA
    Am J Physiol Heart Circ Physiol 293:H3768-71. 2007
    ..Thus, myocyte autonomous inhibition of PKCalpha protects the adult heart from decompensation and dilated cardiomyopathy after infarction injury in association with a primary enhancement in contractility...
  45. pmc Role of the acidic N' region of cardiac troponin I in regulating myocardial function
    Sakthivel Sadayappan
    Division of Molecular Cardiovascular Biology, Cincinnati Children s Hospital Medical Center, 3333 Burnet Ave, Cincinnati, OH 45229 3039, USA
    FASEB J 22:1246-57. 2008
    ....
  46. ncbi Regulation of cardiomyocyte proliferation and myocardial growth during development by FOXO transcription factors
    Heather J Evans-Anderson
    Division of Molecular Cardiovascular Biology, Cincinnati Children s Hospital Medical Center, Ohio 45229, USA
    Circ Res 102:686-94. 2008
    ..These data support FOXO transcription factors as negative regulators of cardiomyocyte proliferation and promoters of neonatal cell cycle withdrawal during heart development...
  47. pmc Cardioprotective stimuli mediate phosphoinositide 3-kinase and phosphoinositide dependent kinase 1 nuclear accumulation in cardiomyocytes
    Marta Rubio
    SDSU Heart Institute, Department of Biology, San Diego State University, 5500 Campanile Drive, San Diego, CA 92182, USA
    J Mol Cell Cardiol 47:96-103. 2009
    ..These findings demonstrate the presence of a dynamically regulated nuclear-associated signaling cascade involving PI3K and PDK that presumably influences nuclear Akt activation...
  48. pmc Cardiac myosin binding protein-C phosphorylation in a {beta}-myosin heavy chain background
    Sakthivel Sadayappan
    Department of Pediatrics, Cincinnati Children s Hospital Medical Center, Ohio, USA
    Circulation 119:1253-62. 2009
    ..We determined the effect(s) of cMyBP-C phosphorylation in a beta-MyHC transgenic mouse heart in which >80% of the alpha-MyHC was replaced by beta-MyHC, which is the predominant myosin isoform in human cardiac muscle...
  49. pmc Interaction between TAK1-TAB1-TAB2 and RCAN1-calcineurin defines a signalling nodal control point
    Qinghang Liu
    Department of Pediatrics, University of Cincinnati, Cincinnati Children s Hospital Medical Center, and the Howard Hughes Medical Institute, Cincinnati, Ohio 45229, USA
    Nat Cell Biol 11:154-61. 2009
    ....
  50. pmc Genetic manipulation of periostin expression in the heart does not affect myocyte content, cell cycle activity, or cardiac repair
    Angela Lorts
    Department of Pediatrics, Division of Cardiology, University of Cincinnati, Cincinnati Children s Hospital Medical Center, Ohio, USA
    Circ Res 104:e1-7. 2009
    ..Periostin is a regulator of cardiac remodeling and hypertrophy and may be a reasonable pharmacological target to mitigate heart failure, but manipulation of this protein appears to have no obvious effect on myocardial regeneration...
  51. pmc With great power comes great responsibility: using mouse genetics to study cardiac hypertrophy and failure
    Jeffery D Molkentin
    Department of Pediatrics, University of Cincinnati, Division of Molecular Cardiovascular Biology, Children s Hospital Medical Center, Cincinnati, OH, USA
    J Mol Cell Cardiol 46:130-6. 2009
    ....
  52. pmc DUSP6 (MKP3) null mice show enhanced ERK1/2 phosphorylation at baseline and increased myocyte proliferation in the heart affecting disease susceptibility
    Marjorie Maillet
    Department of Pediatrics, University of Cincinnati, Cincinnati Children s Hospital Medical Center, Cincinnati, Ohio 45229 3039, USA
    J Biol Chem 283:31246-55. 2008
    ..These results demonstrate that ERK1/2 signaling is physiologically restrained by DUSP6 in coordinating cellular development and survival characteristics, directly impacting disease-responsiveness in adulthood...
  53. pmc Protein misfolding and cardiac disease: establishing cause and effect
    J Scott Pattison
    Department of Pediatrics, Division of Molecular Cardiovascular Biology, Cincinnati Children s Hospital Medical Center, Cincinnati, Ohio, USA
    Autophagy 4:821-3. 2008
    ..Evidence of increased autophagy and necrosis accompanied the PQ83 cardiomyocyte pathology. The data confirm that protein misfolding resulting in intracellular PAO accumulation is sufficient to cause cardiomyocyte death and heart failure...
  54. pmc Genetic approaches for changing the heart and dissecting complex syndromes
    Michael Alice Moga
    Department of Pediatrics, MLC7020, Cincinnati Children s Hospital Medical Center, Cincinnati, OH, 45229 3039, USA
    J Mol Cell Cardiol 45:148-55. 2008
    ..Increasingly precise and modifiable animal models of human cardiac disease will allow researchers to determine not only pathogenesis, but also guide treatment and the development of novel therapies...
  55. pmc Does contractile Ca2+ control calcineurin-NFAT signaling and pathological hypertrophy in cardiac myocytes?
    Steven R Houser
    Department of Physiology, Temple University School of Medicine, 3400 North Broad Street, Philadelphia, PA 19140, USA
    Sci Signal 1:pe31. 2008
    ..Here, we critically review evidence that supports the hypothesis that calcineurin-NFAT signaling is regulated by contractile Ca(2+) transients in cardiac myocytes...
  56. pmc The Gordon Wilson Lecture: neurohormonal signaling pathways that link cardiac growth and death
    Gerald W Dorn
    Center for Molecular Cardiovascular Research, University of Cincinnati, Cincinnati, Ohio, USA
    Trans Am Clin Climatol Assoc 118:137-52. 2007
    ....
  57. pmc Myocardial induction of nucleostemin in response to postnatal growth and pathological challenge
    Sailay Siddiqi
    San Diego State University Heart Institute and Department of Biology, San Diego State University, CA 92182, USA
    Circ Res 103:89-97. 2008
    ....
  58. pmc Cardiomyocyte expression of a polyglutamine preamyloid oligomer causes heart failure
    J Scott Pattison
    Department of Pediatrics, Division of Molecular Cardiovascular Biology, Cincinnati Children s Hospital Medical Center, Cincinnati, OH 45229, USA
    Circulation 117:2743-51. 2008
    ....
  59. pmc Genetic and pharmacologic inhibition of mitochondrial-dependent necrosis attenuates muscular dystrophy
    Douglas P Millay
    Department of Pediatrics, University of Cincinnati, Cincinnati Children s Hospital Medical Center, 3333 Burnet Avenue, Cincinnati, Ohio 45229, USA
    Nat Med 14:442-7. 2008
    ..Thus, mitochondrial-dependent necrosis represents a prominent disease mechanism in muscular dystrophy, suggesting that inhibition of cyclophilin D could provide a new pharmacologic treatment strategy for these diseases...
  60. ncbi Neural crest cells retain multipotential characteristics in the developing valves and label the cardiac conduction system
    Tomoki Nakamura
    Department of Pediatrics, Division of Molecular Cardiovascular Biology, Children s Hospital Research Foundation, Cincinnati, Ohio 45229 3039, USA
    Circ Res 98:1547-54. 2006
    ..These results suggest that cardiac NCCs contribute to the mature valves and the cardiac conduction system and retain multipotent characteristics late in development...

Research Grants30

  1. CARDIOVASCULAR DYNAMICS AND THEIR CONTROL
    John E Hall; Fiscal Year: 2013
    ..End of Abstract) ..