Jeffery Molkentin

Summary

Affiliation: Cincinnati Children's Hospital Medical Center
Country: USA

Publications

  1. pmc Targeted inhibition of p38 MAPK promotes hypertrophic cardiomyopathy through upregulation of calcineurin-NFAT signaling
    Julian C Braz
    Department of Pediatrics, University of Cincinnati, Children s Hospital Medical Center, Cincinnati, Ohio, USA
    J Clin Invest 111:1475-86. 2003
  2. pmc Apoptosis repressor with a CARD domain (ARC) restrains Bax-mediated pathogenesis in dystrophic skeletal muscle
    Jennifer Davis
    Department of Pediatrics, Cincinnati Children s Hospital Medical Center, University of Cincinnati, Cincinnati, Ohio, United States of America
    PLoS ONE 8:e82053. 2013
  3. pmc Heart-specific deletion of CnB1 reveals multiple mechanisms whereby calcineurin regulates cardiac growth and function
    Marjorie Maillet
    Department of Pediatrics, University of Cincinnati, Cincinnati Children s Hospital Medical Center, Howard Hughes Medical Institute, Cincinnati, Ohio 45229 3039, USA
    J Biol Chem 285:6716-24. 2010
  4. pmc Modulation of chromatin position and gene expression by HDAC4 interaction with nucleoporins
    Izhak Kehat
    Department of Pediatrics, Cincinnati Children s Hospital Medical Center, University of Cincinnati, Cincinnati, OH 45229, USA
    J Cell Biol 193:21-9. 2011
  5. pmc Parsing the roles of the transcription factors GATA-4 and GATA-6 in the adult cardiac hypertrophic response
    Jop H van Berlo
    Department of Pediatrics, Cincinnati Children s Hospital Medical Center, University of Cincinnati, Ohio, United States of America
    PLoS ONE 8:e84591. 2013
  6. pmc CIB1 is a regulator of pathological cardiac hypertrophy
    Joerg Heineke
    Howard Hughes Medical Institute, Department of Pediatrics, University of Cincinnati, Cincinnati, OH, USA
    Nat Med 16:872-9. 2010
  7. pmc Parsing good versus bad signaling pathways in the heart: role of calcineurin-nuclear factor of activated T-cells
    Jeffery D Molkentin
    Department of Pediatrics, Cincinnati Children s Hospital Medical Center, University of Cincinnati, Howard Hughes Medical Institute, Cincinnati, OH 45229, USA
    Circ Res 113:16-9. 2013
  8. doi Unrestrained p38 MAPK activation in Dusp1/4 double-null mice induces cardiomyopathy
    Mannix Auger-Messier
    Department of Pediatrics, Cincinnati Children s Hospital Medical Center, Cincinnati, OH 45229, USA
    Circ Res 112:48-56. 2013
  9. pmc Inhibition of PKCα/β with ruboxistaurin antagonizes heart failure in pigs after myocardial infarction injury
    Dennis Ladage
    Cardiovascular Research Center, Mount Sinai School of Medicine, New York, NY, USA
    Circ Res 109:1396-400. 2011
  10. 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

Research Grants

  1. MOLECULAR PATHWAYS CONTROLLING CARDIAC GENE EXPRESSION
    Jeffery Molkentin; Fiscal Year: 2007
  2. CARDIAC HYPERTROPHIC INTRACELLULAR SIGNALING PATHWAYS
    Jeffery Molkentin; Fiscal Year: 2005
  3. MOLECULAR PATHWAYS CONTROLLING CARDIAC GENE EXPRESSION
    Jeffery Molkentin; Fiscal Year: 2006
  4. CARDIAC HYPERTROPHIC INTRACELLULAR SIGNALING PATHWAYS
    Jeffery Molkentin; Fiscal Year: 2006
  5. Mitochondrial Regulated Cardiac Myocyte Death
    Jeffery Molkentin; Fiscal Year: 2006
  6. Mitochondrial Regulated Cardiac Myocyte Death
    Jeffery Molkentin; Fiscal Year: 2007
  7. CARDIAC HYPERTROPHIC INTRACELLULAR SIGNALING PATHWAYS
    Jeffery Molkentin; Fiscal Year: 2007
  8. CARDIAC HYPERTROPHIC INTRACELLULAR SIGNALING PATHWAYS
    Jeffery Molkentin; Fiscal Year: 2009
  9. MOLECULAR PATHWAYS CONTROLLING CARDIAC GENE EXPRESSION
    Jeffery Molkentin; Fiscal Year: 2005
  10. CARDIAC HYPERTROPHIC INTRACELLULAR SIGNALING PATHWAYS
    Jeffery Molkentin; Fiscal Year: 2004

Collaborators

Detail Information

Publications77

  1. pmc Targeted inhibition of p38 MAPK promotes hypertrophic cardiomyopathy through upregulation of calcineurin-NFAT signaling
    Julian C Braz
    Department of Pediatrics, University of Cincinnati, Children s Hospital Medical Center, Cincinnati, Ohio, USA
    J Clin Invest 111:1475-86. 2003
    ..Collectively, these observations indicate that reduced p38 signaling in the heart promotes myocyte growth through a mechanism involving enhanced calcineurin-NFAT signaling...
  2. pmc Apoptosis repressor with a CARD domain (ARC) restrains Bax-mediated pathogenesis in dystrophic skeletal muscle
    Jennifer Davis
    Department of Pediatrics, Cincinnati Children s Hospital Medical Center, University of Cincinnati, Cincinnati, Ohio, United States of America
    PLoS ONE 8:e82053. 2013
    ..Thus Arc deficiency in dystrophic muscle exacerbates disease pathogenesis due to a Bax-mediated sensitization of mitochondria-dependent death mechanisms. ..
  3. pmc Heart-specific deletion of CnB1 reveals multiple mechanisms whereby calcineurin regulates cardiac growth and function
    Marjorie Maillet
    Department of Pediatrics, University of Cincinnati, Cincinnati Children s Hospital Medical Center, Howard Hughes Medical Institute, Cincinnati, Ohio 45229 3039, USA
    J Biol Chem 285:6716-24. 2010
    ..Loss of calcineurin also directly impacted cellular proliferation in the postnatal developing heart. These results reveal multiple mechanisms whereby calcineurin regulates cardiac development and myocyte contractility...
  4. pmc Modulation of chromatin position and gene expression by HDAC4 interaction with nucleoporins
    Izhak Kehat
    Department of Pediatrics, Cincinnati Children s Hospital Medical Center, University of Cincinnati, Cincinnati, OH 45229, USA
    J Cell Biol 193:21-9. 2011
    ..We thus propose a novel mechanism of action for HDAC4, suggesting it can function to dynamically regulate gene expression through changes in chromatin-nucleoporin association...
  5. pmc Parsing the roles of the transcription factors GATA-4 and GATA-6 in the adult cardiac hypertrophic response
    Jop H van Berlo
    Department of Pediatrics, Cincinnati Children s Hospital Medical Center, University of Cincinnati, Ohio, United States of America
    PLoS ONE 8:e84591. 2013
    ....
  6. pmc CIB1 is a regulator of pathological cardiac hypertrophy
    Joerg Heineke
    Howard Hughes Medical Institute, Department of Pediatrics, University of Cincinnati, Cincinnati, OH, USA
    Nat Med 16:872-9. 2010
    ..Thus, CIB1 functions as a previously undescribed regulator of cardiac hypertrophy through its ability to regulate the association of calcineurin with the sarcolemma and its activation...
  7. pmc Parsing good versus bad signaling pathways in the heart: role of calcineurin-nuclear factor of activated T-cells
    Jeffery D Molkentin
    Department of Pediatrics, Cincinnati Children s Hospital Medical Center, University of Cincinnati, Howard Hughes Medical Institute, Cincinnati, OH 45229, USA
    Circ Res 113:16-9. 2013
    ..Since this time we and others have continued to uncover how this signaling effector pathway functions in the heart in regulating specific aspects of the growth response during disease and with exercise...
  8. doi Unrestrained p38 MAPK activation in Dusp1/4 double-null mice induces cardiomyopathy
    Mannix Auger-Messier
    Department of Pediatrics, Cincinnati Children s Hospital Medical Center, Cincinnati, OH 45229, USA
    Circ Res 112:48-56. 2013
    ..A family of dual-specificity phosphatases (DUSPs) directly inactivates each of the MAPK terminal effectors, potentially serving a cardioprotective role...
  9. pmc Inhibition of PKCα/β with ruboxistaurin antagonizes heart failure in pigs after myocardial infarction injury
    Dennis Ladage
    Cardiovascular Research Center, Mount Sinai School of Medicine, New York, NY, USA
    Circ Res 109:1396-400. 2011
    ..Pharmacological inhibition of PKCα/β with Ro-32-0432, Ro-31-8220 or ruboxistaurin (LY333531) similarly enhances cardiac function and antagonizes heart failure in multiple models of disease in both mice and rats...
  10. 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...
  11. pmc Analysis of the transcriptional activity of endogenous NFAT5 in primary cells using transgenic NFAT-luciferase reporter mice
    Beatriz Morancho
    Immunology Unit, Department of Experimental and Health Sciences, Universitat Pompeu Fabra, Barcelona, Spain
    BMC Mol Biol 9:13. 2008
    ..Since the NFAT site of this reporter was very similar to an optimal NFAT5 site, we tested whether this reporter could detect the activation of NFAT5 in transgenic cells...
  12. pmc Dichotomy of Ca2+ in the heart: contraction versus intracellular signaling
    Jeffery D Molkentin
    Cincinnati Children s Hospital Medical Center, University of Cincinnati, Cincinnati, Ohio 45229, USA
    J Clin Invest 116:623-6. 2006
    ....
  13. ncbi Calcineurin-NFAT signaling regulates the cardiac hypertrophic response in coordination with the MAPKs
    Jeffery D Molkentin
    Division of Molecular Cardiovascular Biology, Department of Pediatrics, Cincinnati Children s Hospital Medical Center, 3333 Burnet Avenue, Cincinnati, OH 45229 3039, USA
    Cardiovasc Res 63:467-75. 2004
    ..Thus, an emerging paradigm suggests that calcineurin-NFAT and MAPK signaling pathways are inter-dependent and together orchestrate the cardiac hypertrophic response...
  14. ncbi Contribution of MKP-1 regulation of p38 to endotoxin tolerance
    Marianne Nimah
    Division of Critical Care Medicine, Cincinnati Children s Hospital Research Foundation, University of Cincinnati Medical School, Cincinnati, Ohio 45229 3039, USA
    Shock 23:80-7. 2005
    ..wild type) mice (24% vs. 72% reductions, respectively). These data demonstrate that the dual specific phosphatase MKP-1 is an important mediator of endotoxin tolerance via p38 regulation...
  15. doi TRPC channels as effectors of cardiac hypertrophy
    Petra Eder
    Department of Pediatrics, Division of Molecular Cardiovascular Biology, Howard Hughes Medical Institute, Cincinnati Children s Hospital Medical Center, 240 Albert Sabin Way, Cincinnati, OH 45229 3039, USA
    Circ Res 108:265-72. 2011
    ....
  16. pmc Placental growth factor regulates cardiac adaptation and hypertrophy through a paracrine mechanism
    Federica Accornero
    Howard Hughes Medical Institute, Cincinnati Children s Hospital Medical Center, 240 Albert Sabin Way, Cincinnati, OH 45229, USA
    Circ Res 109:272-80. 2011
    ....
  17. pmc Extracellular signal-regulated kinases 1 and 2 regulate the balance between eccentric and concentric cardiac growth
    Izhak Kehat
    Department of Pediatrics, Division of Molecular Cardiovascular Biology, and Howard Hughes Medical Institute, Cincinnati Children s Hospital Medical Center, 240 Albert Sabin Way, Cincinnati, OH 45229 3039, USA
    Circ Res 108:176-83. 2011
    ..The signaling pathways that control eccentric versus concentric heart growth are not well understood...
  18. 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...
  19. ncbi Calcium-calcineurin signaling in the regulation of cardiac hypertrophy
    Benjamin J Wilkins
    Division of Molecular Cardiovascular Biology, Cincinnati Children s Hospital Medical Center, Cincinnati, OH 45229 3039, USA
    Biochem Biophys Res Commun 322:1178-91. 2004
    ..Finally, we will discuss emerging theories as to the mechanisms whereby alterations in intracellular calcium handling might stimulate calcineurin within the context of a contractile cell continually experiencing calcium flux...
  20. pmc MEKK1 transduces activin signals in keratinocytes to induce actin stress fiber formation and migration
    Lin Zhang
    Department of Environmental Health, University of Cincinnati, 123 E Shields St, Cincinnati, OH 45267 0056, USA
    Mol Cell Biol 25:60-5. 2005
    ..Together, these pathways lead to the control of actin cytoskeleton reorganization and epithelial cell migration, contributing to the physiologic and pathological effects of activins on epithelial morphogenesis...
  21. ncbi MEK1-ERK2 signaling pathway protects myocardium from ischemic injury in vivo
    Daniel J Lips
    Department of Cardiology, Maastricht University, and Heart Lung Center Utrecht, Maastricht and Utrecht, Netherlands
    Circulation 109:1938-41. 2004
    ..Specifically, activation of the extracellular signal-regulated kinases 1/2 (ERK1/2) has been associated with cardioprotection, likely through antagonism of apoptotic regulatory pathways...
  22. ncbi STRESS signaling pathways that modulate cardiac myocyte apoptosis
    Christopher P Baines
    Division of Molecular Cardiovascular Biology, Department of Pediatrics, Cincinnati Children s Hospital Medical Center, 3333 Burnet Avenue, Cincinnati, OH 45229 3039, USA
    J Mol Cell Cardiol 38:47-62. 2005
    ....
  23. pmc Direct and indirect interactions between calcineurin-NFAT and MEK1-extracellular signal-regulated kinase 1/2 signaling pathways regulate cardiac gene expression and cellular growth
    Bastiano Sanna
    Division of Molecular Cardiovascular Biology, Cincinnati Children s Hospital Medical Center, 3333 Burnet Ave, MLC7020, Cincinnati, OH 45229 3039, USA
    Mol Cell Biol 25:865-78. 2005
    ..Collectively, these results indicate that calcineurin-NFAT and MEK1-ERK1/2 pathways constitute a codependent signaling module in cardiomyocytes that coordinately regulates the growth response through two distinct mechanisms...
  24. pmc Calreticulin signals upstream of calcineurin and MEF2C in a critical Ca(2+)-dependent signaling cascade
    Jeffrey Lynch
    Department of Biochemistry, University of Alberta, Edmonton, Alberta, Canada T6G 2H7
    J Cell Biol 170:37-47. 2005
    ..Our study illustrates the existence of a positive feedback mechanism that ensures an adequate supply of releasable Ca(2+) is maintained within the cell for activation of calcineurin and, subsequently, for proper functioning of MEF2C...
  25. pmc Regulation of calcineurin through transcriptional induction of the calcineurin A beta promoter in vitro and in vivo
    Toru Oka
    Cincinnati Children s Hospital Medical Center, Division of Molecular Cardiovascular Biology, 3333 Burnet Ave, MLC7020, Cincinnati OH 45229 3039, USA
    Mol Cell Biol 25:6649-59. 2005
    ....
  26. ncbi Regulation of cardiac hypertrophy by intracellular signalling pathways
    Joerg Heineke
    Department of Pediatrics, University of Cincinnati, Children s Hospital Medical Center, Division of Molecular Cardiovascular Biology, 3333 Burnet Ave, Cincinnati, Ohio 45229, USA
    Nat Rev Mol Cell Biol 7:589-600. 2006
    ..Recent findings in genetically modified animal models implicate important intermediate signal-transduction pathways in the coordination of heart growth following physiological and pathological stimulation...
  27. ncbi DSCR1 gene expression is dependent on NFATc1 during cardiac valve formation and colocalizes with anomalous organ development in trisomy 16 mice
    Alexander W Lange
    Division of Molecular Cardiovascular Biology, Children s Medical Center Cincinnati ML 7020, Cincinnati, OH 45229, USA
    Dev Biol 266:346-60. 2004
    ....
  28. pmc Extracellular signal-regulated kinase 2 interacts with and is negatively regulated by the LIM-only protein FHL2 in cardiomyocytes
    Nicole H Purcell
    Department of Pediatrics, University of Cincinnati, Children s Hospital Medical Center, Cincinnati, Ohio 45229 3039, USA
    Mol Cell Biol 24:1081-95. 2004
    ..Collectively, these results suggest that FHL2 serves a repressor function in cardiomyocytes through its ability to inhibit ERK1/2 transcriptional coupling...
  29. ncbi Calcineurin/NFAT coupling participates in pathological, but not physiological, cardiac hypertrophy
    Benjamin J Wilkins
    Division of Molecular Cardiovascular Biology, Department of Pediatrics, Children s Hospital Medical Center, 3333 Burnet Ave, Cincinnati, Ohio 45229 3039, USA
    Circ Res 94:110-8. 2004
    ....
  30. pmc Targeted disruption of NFATc3, but not NFATc4, reveals an intrinsic defect in calcineurin-mediated cardiac hypertrophic growth
    Benjamin J Wilkins
    Division of Molecular Cardiovascular Biology, Department of Pediatrics, Children s Hospital Medical Center, Cincinnati Ohio 45229 3039, USA
    Mol Cell Biol 22:7603-13. 2002
    ..NFATc3-null mice also demonstrated attenuated pressure overload- and angiotensin II-induced cardiac hypertrophy. These results provide genetic evidence that calcineurin-regulated responses require NFAT effectors in vivo...
  31. ncbi Calcineurin and NFAT4 induce chondrogenesis
    Masuhiro Tomita
    Department of Pathology, University of Texas Health Science Center, San Antonio 78229, USA
    J Biol Chem 277:42214-8. 2002
    ..Furthermore, activated NFAT4 induced BMP2 gene expression. These results have important implications for the effects of NFATs during development and adaptive responses...
  32. ncbi Requirement of nuclear factor of activated T-cells in calcineurin-mediated cardiomyocyte hypertrophy
    Eva van Rooij
    Department of Cardiology, Cardiovascular Research Institute Maastricht, University Hospital, P Debyelaan 25, The Netherlands
    J Biol Chem 277:48617-26. 2002
    ..These results indicate that multiple NFAT isoforms are expressed in cardiomyocytes where they function as necessary transducers of calcineurin in facilitating cardiomyocyte hypertrophy...
  33. pmc Inhibition of calcineurin-NFAT hypertrophy signaling by cGMP-dependent protein kinase type I in cardiac myocytes
    Beate Fiedler
    Department of Cardiology and Angiology, Hannover Medical School, 30625 Hannover, Germany
    Proc Natl Acad Sci U S A 99:11363-8. 2002
    ..Inhibition of calcineurin-NFAT signaling by PKG I provides a framework for understanding how NO inhibits cardiac myocyte hypertrophy...
  34. pmc Defective T cell development and function in calcineurin A beta -deficient mice
    Orlando F Bueno
    Division of Molecular Cardiovascular Biology, Department of Pediatrics, Children s Hospital Medical Center, 3333 Burnet Avenue, Cincinnati, OH 45229 3039, USA
    Proc Natl Acad Sci U S A 99:9398-403. 2002
    ..These results establish a critical role for CnA beta signaling in regulating T cell development and activation in vivo...
  35. ncbi The transcription factors GATA4 and dHAND physically interact to synergistically activate cardiac gene expression through a p300-dependent mechanism
    Yan Shan Dai
    Department of Pediatrics, University of Cincinnati, Children s Hospital Medical Center, Cincinnati, Ohio 45229 3039, USA
    J Biol Chem 277:24390-8. 2002
    ....
  36. ncbi Temporal activation of c-Jun N-terminal kinase in adult transgenic heart via cre-loxP-mediated DNA recombination
    Brian G Petrich
    Department of Physiology, University of Maryland School of Medicine, 655 W Baltimore Street, Baltimore, MD 21201, USA
    FASEB J 17:749-51. 2003
    ..Our data also demonstrated that the inducible gene-switch approach reported here may also be applicable in other studies to achieve efficient, tissue-specific, and temporally regulated genetic manipulation in intact animals...
  37. ncbi NFATc3 and NFATc4 are required for cardiac development and mitochondrial function
    Paul B Bushdid
    Division of Molecular Cardiovascular Biology, Children s Hospital Medical Center Cincinnati, ML 7020, 3333 Burnet Ave, Cincinnati, Ohio 45229, USA
    Circ Res 92:1305-13. 2003
    ..Together, these data support the hypothesis that loss of NFAT activity in the heart results in a deficiency in mitochondrial energy metabolism required for cardiac morphogenesis and function...
  38. pmc Requirement of transcription factor NFAT in developing atrial myocardium
    William Schubert
    Dept of Molecular Pharmacology, Albert Einstein College of Medicine, Jack and Pearl Resnick Campus, Bronx, NY 10461, USA
    J Cell Biol 161:861-74. 2003
    ..Thus, regulation of cytoskeletal protein gene expression by NFAT may be important for the structural architecture of the developing atrial myocardium...
  39. ncbi Redefining the roles of p38 and JNK signaling in cardiac hypertrophy: dichotomy between cultured myocytes and animal models
    Qiangrong Liang
    Division of Molecular Cardiovascular Biology, Department of Pediatrics, Cincinnati Children s Hospital Medical Center, 3333 Burnet Avenue, Cincinnati, OH 45229 3039, USA
    J Mol Cell Cardiol 35:1385-94. 2003
    ..However, SAPK signaling is likely maladaptive, despite its putative anti-hypertrophic role in vivo, given the observation of dilated cardiomyopathy and heart failure in gain-of-function transgenic models...
  40. ncbi Calcineurin Abeta gene targeting predisposes the myocardium to acute ischemia-induced apoptosis and dysfunction
    Orlando F Bueno
    Department of Pediatrics, Division of Molecular Cardiovascular Biology, Children s Hospital Medical Center, Cincinnati, Ohio 45229 3039, USA
    Circ Res 94:91-9. 2004
    ..These results represent the first genetic loss-of-function data showing a prosurvival role for calcineurin-NFAT signaling in the heart...
  41. pmc c-Jun N-terminal kinases (JNK) antagonize cardiac growth through cross-talk with calcineurin-NFAT signaling
    Qiangrong Liang
    Department of Pediatrics, University of Cincinnati, Children s Hospital Medical Center, 3333 Burnet Avenue, Cincinnati, OH 45229 3039, USA
    EMBO J 22:5079-89. 2003
    ..These results also suggest that myocardial JNK activation is primarily dedicated to modulating calcineurin-NFAT signaling in the regulation of differentiated heart growth...
  42. ncbi Divergent signaling pathways converge on GATA4 to regulate cardiac hypertrophic gene expression
    Qiangrong Liang
    J Mol Cell Cardiol 34:611-6. 2002
  43. ncbi Is nuclear factor kappaB an attractive therapeutic target for treating cardiac hypertrophy?
    Nicole H Purcell
    Circulation 108:638-40. 2003
  44. ncbi Calcineurin transgenic mice have mitochondrial dysfunction and elevated superoxide production
    M R Sayen
    The Scripps Research Institute, La Jolla, California 92037, USA
    Am J Physiol Cell Physiol 284:C562-70. 2003
    ..Taken together, these data indicate that calcineurin signaling affects mitochondrial energetics and superoxide production. The excessive production of superoxide may contribute to the development of cardiac failure...
  45. doi Calcineurin-induced energy wasting in a transgenic mouse model of heart failure
    Ilka Pinz
    NMR Laboratory for Physiological Chemistry, Division of Cardiovascular Medicine, Department of Medicine, Brigham and Women s Hospital, Boston, MA 02115, USA
    Am J Physiol Heart Circ Physiol 294:H1459-66. 2008
    ....
  46. ncbi Calcineurin and hypertrophic heart disease: novel insights and remaining questions
    Orlando F Bueno
    Division of Molecular Cardiovascular Biology, Department of Pediatrics, Children s Hospital Medical Center, Cincinnati OH, USA
    Cardiovasc Res 53:806-21. 2002
    ....
  47. pmc Periostin is required for maturation and extracellular matrix stabilization of noncardiomyocyte lineages of the heart
    Paige Snider
    Cardiovascular Development Group, Herman B Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, USA
    Circ Res 102:752-60. 2008
    ..Thus, peri(lacZ) knockouts provide a new model of viable latent valve disease...
  48. 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...
  49. pmc Cardiomyocyte GATA4 functions as a stress-responsive regulator of angiogenesis in the murine heart
    Joerg Heineke
    Department of Pediatrics, Cincinnati Children s Hospital Medical Center, University of Cincinnati, Cincinnati, Ohio 45229, USA
    J Clin Invest 117:3198-210. 2007
    ..To our knowledge, these results demonstrate [corrected] a previously unrecognized function for GATA4 as a regulator of cardiac angiogenesis through a nonhypoxic, load, and/or disease-responsive mechanism...
  50. pmc PKC alpha regulates the hypertrophic growth of cardiomyocytes through extracellular signal-regulated kinase1/2 (ERK1/2)
    Julian C Braz
    Department of Pediatrics, University of Cincinnati, Children s Hospital Medical Center, Cincinnati, OH 45229, USA
    J Cell Biol 156:905-19. 2002
    ..These results implicate PKC alpha as a necessary mediator of cardiomyocyte hypertrophic growth, in part, through a ERK1/2-dependent signaling pathway...
  51. ncbi Inhibition of calcineurin and sarcolemmal Ca2+ influx protects cardiac morphology and ventricular function in K(v)4.2N transgenic mice
    Rajan Sah
    Department of Physiology and the Division of Cardiology, University Health Network, University of Toronto, Toronto, Canada
    Circulation 105:1850-6. 2002
    ..2N mice results from elevations in intracellular calcium ([Ca2+]i) secondary to AP prolongation and investigated the putative roles of calcineurin activation in heart disease development of K(v)4.2N mice...
  52. ncbi Reduction of I(to) causes hypertrophy in neonatal rat ventricular myocytes
    Zamaneh Kassiri
    Department of Physiology, Heart and Stroke Richard Lewar Center, University of Toronto, Toronto, Canada
    Circ Res 90:578-85. 2002
    ..2)N infection were prevented by blocking Ca2+ entry and excitability with verapamil or high [K+]o. Our studies suggest that reductions of K(v4.2/3)-based I(to) play a role in hypertrophy signaling by activation of calcineurin...
  53. ncbi Insulin inhibits PDGF-directed VSMC migration via NO/ cGMP increase of MKP-1 and its inactivation of MAPKs
    Asha Jacob
    The Diabetes Research Laboratory, Winthrop University Hospital, Mineola 11501, New York
    Am J Physiol Cell Physiol 283:C704-13. 2002
    ..We conclude that insulin inhibition of VSMC migration may be mediated in part by NO/cGMP/cGK Ialpha induction of MKP-1 and consequent inactivation of MAPKs...
  54. ncbi Cardiac function and electrical remodeling of the calcineurin-overexpressed transgenic mouse
    Natalia N Petrashevskaya
    Institute of Molecular Pharmacology and Biophysics, Department of Surgery, Cardiovascular Research Center, University of Cincinnati, 231 Albert Sabin Way, OH 45267, USA
    Cardiovasc Res 54:117-32. 2002
    ....
  55. ncbi Enhanced myocyte contractility and Ca2+ handling in a calcineurin transgenic model of heart failure
    Guoxiang Chu
    Department of Pharmacology and Cell Biophysics, University of Cincinnati College of Medicine, 231 Albert B Sabin Way, OH 45267 0575, USA
    Cardiovasc Res 54:105-16. 2002
    ..We examined whether defects in cardiomyocyte Ca2+ handling properties contribute to the impaired cardiac function in calcineurin transgenic mice...
  56. pmc Evidence from a genetic fate-mapping study that stem cells refresh adult mammalian cardiomyocytes after injury
    Patrick C H Hsieh
    Cardiovascular Division, Department of Medicine, Brigham and Women s Hospital, Harvard Medical School, Cambridge, Massachusetts 02139, USA
    Nat Med 13:970-4. 2007
    ..5% in areas bordering a myocardial infarction, 76.6% in areas away from a myocardial infarction, and 75.7% in hearts subjected to pressure overload, indicating that stem cells or precursor cells had refreshed the cardiomyocytes...
  57. pmc Mediating ERK 1/2 signaling rescues congenital heart defects in a mouse model of Noonan syndrome
    Tomoki Nakamura
    Cincinnati Children s Hospital Medical Center, The Children s Hospital Research Foundation, Division of Molecular Cardiovascular Biology, Cincinnati, Ohio 45229 3039, USA
    J Clin Invest 117:2123-32. 2007
    ....
  58. ncbi Myocyte enhancer factors 2A and 2C induce dilated cardiomyopathy in transgenic mice
    Jian Xu
    Departments of Pharmacology and Pediatrics, Cincinnati Children s Hospital Medical Center, University of Cincinnati, Cincinnati, Ohio 45229, USA
    J Biol Chem 281:9152-62. 2006
    ....
  59. ncbi Temporally controlled onset of dilated cardiomyopathy through disruption of the SRF gene in adult heart
    Ara Parlakian
    Molecular Biology of Differentiation, The Université Paris 7, EA300, Paris, France
    Circulation 112:2930-9. 2005
    ..We have shown, using the Cre/loxP system, that cardiac-specific disruption of SRF gene in the embryonic heart results in lethal cardiac defects. The role of SRF in adult heart is unknown...
  60. pmc The DnaJ-related factor Mrj interacts with nuclear factor of activated T cells c3 and mediates transcriptional repression through class II histone deacetylase recruitment
    Yan Shan Dai
    Department of Pediatrics, University of Cincinnati, Cincinnati Children s Hospital Medical Center, Division of Molecular Cardiovascular Biology, 3333 Burnet Ave, MLC7020, Cincinnati, Ohio 45229 3039, USA
    Mol Cell Biol 25:9936-48. 2005
    ..Collectively, our results define a novel response pathway whereby NFATc3 is negatively regulated by class II histone deacetylases through the DnaJ (heat shock protein-40) superfamily member Mrj...
  61. ncbi Inhibition of p38 reduces myocardial infarction injury in the mouse but not pig after ischemia-reperfusion
    Robert A Kaiser
    Dept of Pediatrics, Cincinnati Children s Hospital Medical Center, Univ of Cincinnati, 3333 Burnet Ave, Cincinnati, OH 45229, USA
    Am J Physiol Heart Circ Physiol 289:H2747-51. 2005
    ....
  62. ncbi Activation of GATA-4 by serotonin in pulmonary artery smooth muscle cells
    Yuichiro J Suzuki
    Department of Medicine, Tufts University, Boston, Massachusetts 02111, USA
    J Biol Chem 278:17525-31. 2003
    ..Thus, GATA-4 mediates 5-HT-induced growth of PASMC and may be an important therapeutic target for the prevention of pulmonary hypertension...
  63. pmc A friend within the heart: natriuretic peptide receptor signaling
    Jeffery D Molkentin
    Department of Pediatrics, Children s Hospital Medical Center, Cincinnati, Ohio 45229 3039, USA
    J Clin Invest 111:1275-7. 2003
  64. pmc Cardiomyocytes fuse with surrounding noncardiomyocytes and reenter the cell cycle
    Katsuhisa Matsuura
    Department of Cardiovascular Science and Medicine, Chiba University Graduate School of Medicine, Chiba 260 8670, Japan
    J Cell Biol 167:351-63. 2004
    ..These results suggest that cardiomyocytes fuse with other cells and enter the cell cycle by maintaining their phenotypes...
  65. ncbi Genetic loss of calcineurin blocks mechanical overload-induced skeletal muscle fiber type switching but not hypertrophy
    Stephanie A Parsons
    Department of Pediatrics, University of Cincinnati, Cincinnati Children s Hospital Medical Center, Cincinnati, Ohio 45229 3039, USA
    J Biol Chem 279:26192-200. 2004
    ..We conclude that calcineurin expression is important during myogenesis and fiber-type switching, but not for muscle growth in response to hypertrophic stimuli...
  66. ncbi High glucose activates nuclear factor of activated T cells in native vascular smooth muscle
    Jenny Nilsson
    Department of Experimental Medical Science, Lund University, Sweden
    Arterioscler Thromb Vasc Biol 26:794-800. 2006
    ..Atypical Ca2+ signaling and gene expression are characteristic of vascular dysfunction; however, little is known regarding the effects of high glucose on Ca2+-dependent transcription in the vascular wall...
  67. ncbi Targeted inhibition of p38 mitogen-activated protein kinase antagonizes cardiac injury and cell death following ischemia-reperfusion in vivo
    Robert A Kaiser
    Department of Pediatrics, University of Cincinnati, Children s Hospital Medical Center, Division of Molecular Cardiovascular Biology, Cincinnati, Ohio 45229 3039, USA
    J Biol Chem 279:15524-30. 2004
    ..Collectively, these results indicate that p38 functions as a pro-death signaling effector in both cultured myocytes as well as in the intact heart...
  68. ncbi Renaming the DSCR1/Adapt78 gene family as RCAN: regulators of calcineurin
    Kelvin J A Davies
    Ethel Percy Andrus Gerontology Center, and Division of Molecular and Computational Biology, The University of Southern California, Los Angeles, CA 90089 0191, USA
    FASEB J 21:3023-8. 2007
  69. ncbi Inducible cardiac-restricted expression of enteroviral protease 2A is sufficient to induce dilated cardiomyopathy
    Dingding Xiong
    University of California, San Diego, Department of Medicine, 9500 Gilman Dr, La Jolla, CA 92093, USA
    Circulation 115:94-102. 2007
    ..However, the direct effect of protease 2A in enteroviral cardiomyopathy is less clear because other viral proteins are also expressed with viral infection...
  70. ncbi Involvement of extracellular signal-regulated kinases 1/2 in cardiac hypertrophy and cell death
    Orlando F Bueno
    Department of Pediatrics, University of Cincinnati, Division of Molecular Cardiovascular Biology, Children s Hospital Medical Center, Cincinnati, Ohio 45229 3039, USA
    Circ Res 91:776-81. 2002
    ....
  71. 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
    ....
  72. 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...
  73. ncbi Calcineurin regulates NFAT-dependent iNOS expression and protection of cardiomyocytes: co-operation with Src tyrosine kinase
    Kofo Obasanjo-Blackshire
    Cardiovascular Division, King s College London School of Medicine, Department of Cardiology, The Rayne Institute, St Thomas s Hospital, Lambeth Palace Road, London SE1 7EH, UK
    Cardiovasc Res 71:672-83. 2006
    ..To determine the role of calcineurin and Src tyrosine kinase in the regulation of inducible nitric oxide synthase (iNOS) expression and protection in cardiomyocytes...
  74. pmc The beta-catenin/T-cell factor/lymphocyte enhancer factor signaling pathway is required for normal and stress-induced cardiac hypertrophy
    Xin Chen
    Molecular Cardiology Research Institute, Tufts New England Medical Center and Tufts University School of Medicine, USA
    Mol Cell Biol 26:4462-73. 2006
    ..Thus, our studies, employing complementary models in vivo, implicate beta-catenin/Tcf/Lef signaling as an essential growth-regulatory pathway in terminally differentiated cells...
  75. pmc Direct interaction and reciprocal regulation between ASK1 and calcineurin-NFAT control cardiomyocyte death and growth
    Qinghang Liu
    Department of Pediatrics, University of Cincinnati, Cincinnati Children s Hospital Medical Center, 3333 Burnet Ave, MLC7020, Cincinnati Ohio 45229 3039, USA
    Mol Cell Biol 26:3785-97. 2006
    ....
  76. ncbi PKC-alpha regulates cardiac contractility and propensity toward heart failure
    Julian C Braz
    Department of Pediatrics, University of Cincinnati, Children s Hospital Medical Center, Cincinnati, Ohio 45229 3039, USA
    Nat Med 10:248-54. 2004
    ..Thus, PKC-alpha functions as a nodal integrator of cardiac contractility by sensing intracellular Ca(2+) and signal transduction events, which can profoundly affect propensity toward heart failure...

Research Grants24

  1. MOLECULAR PATHWAYS CONTROLLING CARDIAC GENE EXPRESSION
    Jeffery Molkentin; Fiscal Year: 2007
    ....
  2. CARDIAC HYPERTROPHIC INTRACELLULAR SIGNALING PATHWAYS
    Jeffery Molkentin; Fiscal Year: 2005
    ..Yeast 2-hybrid screening has identified a novel class of cardiac-expressed NFAT inhibiting factors that will be further evaluated in vitro and in vivo. ..
  3. MOLECULAR PATHWAYS CONTROLLING CARDIAC GENE EXPRESSION
    Jeffery Molkentin; Fiscal Year: 2006
    ....
  4. CARDIAC HYPERTROPHIC INTRACELLULAR SIGNALING PATHWAYS
    Jeffery Molkentin; Fiscal Year: 2006
    ..Yeast 2-hybrid screening has identified a novel class of cardiac-expressed NFAT inhibiting factors that will be further evaluated in vitro and in vivo. ..
  5. Mitochondrial Regulated Cardiac Myocyte Death
    Jeffery Molkentin; Fiscal Year: 2006
    ....
  6. Mitochondrial Regulated Cardiac Myocyte Death
    Jeffery Molkentin; Fiscal Year: 2007
    ....
  7. CARDIAC HYPERTROPHIC INTRACELLULAR SIGNALING PATHWAYS
    Jeffery Molkentin; Fiscal Year: 2007
    ..Yeast 2-hybrid screening has identified a novel class of cardiac-expressed NFAT inhibiting factors that will be further evaluated in vitro and in vivo. ..
  8. CARDIAC HYPERTROPHIC INTRACELLULAR SIGNALING PATHWAYS
    Jeffery Molkentin; Fiscal Year: 2009
    ..An elucidation of these regulatory relationships surrounding calcineurin is of considerable disease relevance. ..
  9. MOLECULAR PATHWAYS CONTROLLING CARDIAC GENE EXPRESSION
    Jeffery Molkentin; Fiscal Year: 2005
    ....
  10. CARDIAC HYPERTROPHIC INTRACELLULAR SIGNALING PATHWAYS
    Jeffery Molkentin; Fiscal Year: 2004
    ..Yeast 2-hybrid screening has identified a novel class of cardiac-expressed NFAT inhibiting factors that will be further evaluated in vitro and in vivo. ..
  11. MOLECULAR PATHWAYS CONTROLLING CARDIAC GENE EXPRESSION
    Jeffery Molkentin; Fiscal Year: 2004
    ....
  12. MOLECULAR PATHWAYS CONTROLLING CARDIAC GENE EXPRESSION
    Jeffery Molkentin; Fiscal Year: 1999
    ....
  13. MOLECULAR PATHWAYS CONTROLLING CARDIAC GENE EXPRESSION
    Jeffery Molkentin; Fiscal Year: 2000
    ....
  14. CARDIAC HYPERTROPHIC INTRACELLULAR SIGNALING PATHWAYS
    Jeffery Molkentin; Fiscal Year: 2000
    ..The potential ramifications of the successful elucidation of this pathway are extensive given that cyclosporin A and FK506 are potent inhibitors of calcineurin. ..
  15. MOLECULAR PATHWAYS CONTROLLING CARDIAC GENE EXPRESSION
    Jeffery Molkentin; Fiscal Year: 2001
    ....
  16. CARDIAC HYPERTROPHIC INTRACELLULAR SIGNALING PATHWAYS
    Jeffery Molkentin; Fiscal Year: 2001
    ..The potential ramifications of the successful elucidation of this pathway are extensive given that cyclosporin A and FK506 are potent inhibitors of calcineurin. ..
  17. CARDIAC HYPERTROPHIC INTRACELLULAR SIGNALING PATHWAYS
    Jeffery Molkentin; Fiscal Year: 2002
    ..The potential ramifications of the successful elucidation of this pathway are extensive given that cyclosporin A and FK506 are potent inhibitors of calcineurin. ..
  18. MOLECULAR PATHWAYS CONTROLLING CARDIAC GENE EXPRESSION
    Jeffery Molkentin; Fiscal Year: 2002
    ....
  19. CARDIAC HYPERTROPHIC INTRACELLULAR SIGNALING PATHWAYS
    Jeffery Molkentin; Fiscal Year: 2003
    ..Yeast 2-hybrid screening has identified a novel class of cardiac-expressed NFAT inhibiting factors that will be further evaluated in vitro and in vivo. ..
  20. MOLECULAR PATHWAYS CONTROLLING CARDIAC GENE EXPRESSION
    Jeffery Molkentin; Fiscal Year: 2003
    ....
  21. CARDIAC HYPERTROPHIC INTRACELLULAR SIGNALING PATHWAYS
    Jeffery D Molkentin; Fiscal Year: 2010
    ..An elucidation of these regulatory relationships surrounding calcineurin is of considerable disease relevance. ..
  22. Mitochondrial Regulated Cardiac Myocyte Death
    Jeffery Molkentin; Fiscal Year: 2005
    ....