Jeffery D Molkentin

Howard Hughes Medical Institute, Ashburn, Virginia, United States

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Publications (347)3062.2 Total impact

  • Jop H van Berlo, Jeffery D Molkentin
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    ABSTRACT: Cardiac regeneration is a rapidly evolving and controversial field of research. The identification some 12 years ago of progenitor cells that reside within the heart spurred enthusiasm for cell-based regenerative therapies. However, recent evidence has called into question both the presence of a biologically important stem cell population in the heart and the ability of exogenously derived cells to promote regeneration through direct formation of new cardiomyocytes. Here, we discuss recent developments that suggest an emerging consensus on the ability of different cell types to regenerate the adult mammalian heart.
    Nature medicine. 12/2014; 20(12):1386-93.
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    ABSTRACT: Latent transforming growth factor-β (TGFβ) binding proteins (LTBPs) bind to inactive TGFβ in the extracellular matrix. In mice, muscular dystrophy symptoms are intensified by a genetic polymorphism that changes the hinge region of LTBP, leading to increased proteolytic susceptibility and TGFβ release. We have found that the hinge region of human LTBP4 was also readily proteolysed and that proteolysis could be blocked by an antibody to the hinge region. Transgenic mice were generated to carry a bacterial artificial chromosome encoding the human LTBP4 gene. These transgenic mice displayed larger myofibers, increased damage after muscle injury, and enhanced TGFβ signaling. In the mdx mouse model of Duchenne muscular dystrophy, the human LTBP4 transgene exacerbated muscular dystrophy symptoms and resulted in weaker muscles with an increased inflammatory infiltrate and greater LTBP4 cleavage in vivo. Blocking LTBP4 cleavage may be a therapeutic strategy to reduce TGFβ release and activity and decrease inflammation and muscle damage in muscular dystrophy.
    Science translational medicine 10/2014; 6(259):259ra144. · 10.76 Impact Factor
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    ABSTRACT: -Programmed necrosis (necroptosis) plays an important role in development, tissue homeostasis, and disease pathogenesis. The molecular mechanisms that regulate necroptosis in the heart and its physiological relevance in myocardial remodeling and heart failure remain largely unknown.
    Circulation 10/2014; · 15.20 Impact Factor
  • Jeffery D Molkentin
    Circulation Research 09/2014; 115(8):e21-3. · 11.86 Impact Factor
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    ABSTRACT: Muscular dystrophy (MD) is a disease characterized by skeletal muscle necrosis and the progressive accumulation of fibrotic tissue. While transforming growth factor (TGF)-β has emerged as central effector of MD and fibrotic disease, the cell types in diseased muscle that underlie TGFβ-dependent pathology have not been segregated. Here we generated transgenic mice with myofiber-specific inhibition of TGFβ signaling due to expression of a TGFβ type II receptor dominant negative (dnTGFβRII) truncation mutant. Expression of dnTGFβRII in myofibers mitigated the dystrophic phenotype observed in δ-sarcoglycan-null (Sgcd(-/-)) mice through a mechanism involving reduced myofiber membrane fragility. The dnTGFβRII transgene also reduced muscle injury and improved muscle regeneration after cardiotoxin injury, as well as increased satellite cell numbers and activity. An unbiased global expression analysis revealed a number of potential mechanisms for dnTGFβRII mediated protection, one of which was induction of the antioxidant proteins metallothionein (Mt). Indeed, TGFβ directly inhibited Mt gene expression in vitro, the dnTGFβRII transgene conferred protection against ROS accumulation in dystrophic muscle, and treatment with Mt mimetics protected skeletal muscle upon injury in vivo and improved the membrane stability of dystrophic myofibers. Hence, our results show that the myofibers are central mediators of the deleterious effects associated with TGFβ signaling in MD.
    Human Molecular Genetics 08/2014; · 7.69 Impact Factor
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    ABSTRACT: Rationale: The cellular and molecular basis for post myocardial infarction (MI) structural and functional remodeling is not well understood. Objective: To determine if Ca(2+) influx through transient receptor potential (canonical) (TRPC) channels contributes to post-MI structural and functional remodeling. Methods and Results: TRPC1/3/4/6 channel mRNA increased after MI in mice and was associated with TRPC-mediated Ca(2+) entry. Cardiac myocyte specific expression of a dominant negative (dn: loss of function) TRPC4 channel increased basal myocyte contractility and reduced hypertrophy and cardiac structural and functional remodeling after MI while increasing survival. We used adenovirus-mediated expression of TRPC3/4/6 channels in cultured adult feline myocytes (AFMs) to define mechanistic aspects of these TRPC-related effects. TRPC3/4/6 over expression in AFMs induced calcineurin (Cn)-Nuclear Factor of Activated T cells (NFAT) mediated hypertrophic signaling, which was reliant on caveolae targeting of TRPCs. TRPC3/4/6 expression in AFMs increased rested state contractions and increased spontaneous sarcoplasmic reticulum (SR) Ca(2+) sparks mediated by enhanced phosphorylation of the ryanodine receptor. TRPC3/4/6 expression was associated with reduced contractility and response to catecholamines during steady state pacing, likely due to enhanced SR Ca(2+) leak. Conclusions: Ca(2+) influx through TRPC channels expressed after MI activates pathological cardiac hypertrophy and reduces contractility reserve. Blocking post-MI TRPC activity improved post-MI cardiac structure and function.
    Circulation Research 07/2014; · 11.86 Impact Factor
  • Jason Karch, Jeffery D Molkentin
    Proceedings of the National Academy of Sciences of the United States of America. 07/2014;
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    ABSTRACT: Muscular dystrophies are a group of genetic diseases that lead to muscle wasting and in most cases, premature death. Cytokines and inflammatory factors are released during the disease process where they promote deleterious signaling events that directly participate in myofiber death. Here we show that p38α, a kinase in the greater mitogen-activated protein kinase (MAPK) signaling network, serves as a nodal regulator of disease signaling in dystrophic muscle. Deletion of Mapk14 (p38α encoding gene) in the skeletal muscle of mdx (lacking dystrophin) or sgcd (δ-sarcoglycan encoding gene) null mice resulted in a significant reduction in pathology up to 6 months of age. We also generated MAPK kinase 6 (MKK6) muscle-specific transgenic mice to model heightened p38α disease signaling that occurs in dystrophic muscle, which resulted in severe myofiber necrosis and many hallmarks of muscular dystrophy. Mechanistically, we show that p38α directly induces myofiber death through a mitochondrial-dependent pathway involving direct phosphorylation and activation of the pro-death Bcl-2 family member Bax. Indeed, muscle-specific deletion of Bax, but not the apoptosis regulatory gene Tp53 (encoding p53), significantly reduced dystrophic pathology in the muscles of MKK6 transgenic mice. Moreover, use of a p38 MAPK pharmacologic inhibitor reduced dystrophic disease in Sgcd(-/-) mice suggesting a future therapeutic approach to delay disease.
    Human Molecular Genetics 05/2014; · 7.69 Impact Factor
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    ABSTRACT: If and how the heart regenerates after an injury event is highly debated. c-kit-expressing cardiac progenitor cells have been reported as the primary source for generation of new myocardium after injury. Here we generated two genetic approaches in mice to examine whether endogenous c-kit(+) cells contribute differentiated cardiomyocytes to the heart during development, with ageing or after injury in adulthood. A complementary DNA encoding either Cre recombinase or a tamoxifen-inducible MerCreMer chimaeric protein was targeted to the Kit locus in mice and then bred with reporter lines to permanently mark cell lineage. Endogenous c-kit(+) cells did produce new cardiomyocytes within the heart, although at a percentage of approximately 0.03 or less, and if a preponderance towards cellular fusion is considered, the percentage falls to below approximately 0.008. By contrast, c-kit(+) cells amply generated cardiac endothelial cells. Thus, endogenous c-kit(+) cells can generate cardiomyocytes within the heart, although probably at a functionally insignificant level.
    Nature 05/2014; · 38.60 Impact Factor
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    ABSTRACT: The Mitochondrial Permeability Transition (MPT) pore is a voltage-sensitive unselective channel known to instigate necrotic cell death during cardiac disease. Recent models suggest that the isomerase cyclophilin D (CypD) regulates the MPT pore by binding to either the F0F1-ATP synthase lateral stalk or the mitochondrial phosphate carrier (PiC). Here we confirm that CypD, through its N-terminus, can directly bind PiC. We then generated cardiac-specific mouse strains overexpressing or with decreased levels of mitochondrial PiC to assess the functionality of such interaction. While PiC overexpression had no observable pathologic phenotype, PiC knockdown resulted in cardiac hypertrophy along with decreased ATP levels. Mitochondria isolated from hearts of these mouse lines and their respective non-transgenic controls had no divergent phenotype in terms of oxygen consumption and Ca(2+)-induced MPT, as assessed by swelling and Ca(2+)-retention measurements. These results provide genetic evidence indicating that the mitochondrial PiC is not a critical component of the MPT pore.
    Journal of Molecular and Cellular Cardiology 04/2014; · 5.15 Impact Factor
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    ABSTRACT: Unregulated Ca(2+) entry is thought to underlie muscular dystrophy. Here we generated skeletal muscle-specific transgenic mice expressing the Na(+)/Ca(2+) exchanger 1 (NCX1) to model its known augmentation during muscular dystrophy. The NCX1 transgene induced dystrophic-like disease in all hindlimb musculature, as well as exacerbated the muscle disease phenotypes in δ-sarcoglycan (Sgcd(-/-)), Dysf(-/-), and mdx mouse models of muscular dystrophy. Antithetically, muscle-specific deletion of the Slc8a1 (NCX1) gene diminished hindlimb pathology in Sgcd(-/-) mice. Measured increases in baseline Na(+) and Ca(2+) in dystrophic muscle fibers of the hindlimb musculature predicts a net Ca(2+) influx state due to reverse mode operation of NCX1, which mediates disease. However, the opposite effect is observed in the diaphragm where NCX1 overexpression mildly protects from dystrophic disease through a predicted enhancement in forward mode NCX1 operation that reduces Ca(2+) levels. Indeed, Atp1a2(+/-) (encodes Na(+)/K(+) ATPase α2) mice, which have reduced Na(+) clearance rates that would favor NCX1 reverse mode operation, showed exacerbated disease in the hindlimbs of NCX1 TG mice, similar to treatment with the Na(+)/K(+) ATPase inhibitor digoxin. Treatment of Sgcd(-/-) mice with ranolazine, a broadly acting Na(+) channel inhibitor that should increase NCX1 forward mode operation, reduced muscular pathology.
    Molecular and Cellular Biology 03/2014; · 5.04 Impact Factor
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    ABSTRACT: The mitochondrial phosphate carrier (PiC) is critical for ATP synthesis by serving as the primary means for mitochondrial phosphate import across the inner membrane. In addition to its role in energy production, PiC is hypothesized to have a role in cell death as either a component or a regulator of the mitochondrial permeability transition pore (MPTP) complex. Here, we have generated a mouse model with inducible and cardiac-specific deletion of the Slc25a3 gene (PiC protein). Loss of PiC protein did not prevent MPTP opening, suggesting it is not a direct pore-forming component of this complex. However, Slc25a3 deletion in the heart blunted MPTP opening in response to Ca(2+) challenge and led to a greater Ca(2+) uptake capacity. This desensitization of MPTP opening due to loss or reduction in PiC protein attenuated cardiac ischemic-reperfusion injury, as well as partially protected cells in culture from Ca(2+) overload induced death. Intriguingly, deletion of the Slc25a3 gene from the heart long-term resulted in profound hypertrophy with ventricular dilation and depressed cardiac function, all features that reflect the cardiomyopathy observed in humans with mutations in SLC25A3. Together, these results demonstrate that although the PiC is not a direct component of the MPTP, it can regulate its activity, suggesting a novel therapeutic target for reducing necrotic cell death. In addition, mice lacking Slc25a3 in the heart serve as a novel model of metabolic, mitochondrial-driven cardiomyopathy.Cell Death and Differentiation advance online publication, 21 March 2014; doi:10.1038/cdd.2014.36.
    Cell death and differentiation 03/2014; · 8.24 Impact Factor
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    ABSTRACT: Wound healing after myocardial infarction involves a highly regulated inflammatory response that is initiated by the appearance of neutrophils to clear out dead cells and matrix debris. Neutrophil infiltration is controlled by multiple secreted factors, including the master regulator transforming growth factor beta (TGFβ). Broad inhibition of TGFβ early post-infarction has worsened post-MI remodeling; however, this signaling displays potent cell-specificity and targeted suppression particularly in the myocyte could be beneficial. To test the hypothesis that targeted suppression of myocyte TGFβ signaling suppresses post-infarct remodeling and inflammatory modulation, and identify mechanisms by which this may be achieved. Mice with TGFβ receptor-coupled signaling genetically suppressed only in cardiac myocytes (conditional TGFβ receptor 1 or 2 knockout) displayed marked declines in neutrophil recruitment and accompanying metalloproteinase-9 activation after infarction, and were protected against early onset mortality due to wall rupture. This was a cell-specific effect, as broader inhibition of TGFβ signaling led to 100% early mortality due to rupture. Rather than by altering fibrosis or reducing generation of pro-inflammatory cytokines/chemokines, myocyte-selective TGFβ-inhibition augmented synthesis of a constellation of highly protective cardiokines. These included thrombospondin 4 with associated endoplasmic reticulum stress responses, interleukin-33, follistatin-like 1, and growth and differentiation factor-15 (GDF-15), which is an inhibitor of neutrophil integrin activation and tissue migration. These data reveal a novel role of myocyte canonical TGFβ signaling as a potent regulator of protective cardiokine and neutrophil mediated infarct remodeling.
    Circulation Research 02/2014; · 11.86 Impact Factor
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    ABSTRACT: Muscular dystrophy is a progressive muscle wasting disease that is thought to be initiated by unregulated Ca(2+) influx into myofibers leading to their death. Store-operated Ca(2+) entry (SOCE) through sarcolemmal Ca(2+) selective Orai1 channels in complex with STIM1 in the sarcoplasmic reticulum is one such potential disease mechanism for pathologic Ca(2+) entry. Here we generated a mouse model of STIM1 overexpression in skeletal muscle to determine if this type of Ca(2+) entry could induce muscular dystrophy. Myofibers from muscle-specific STIM1 transgenic mice showed a significant increase in store-operated Ca(2+) entry in skeletal muscle, modeling an observed increase in the same current in dystrophic myofibers. Histological and biochemical analysis of STIM1 transgenic mice showed fulminant muscle disease characterized by myofiber necrosis, swollen mitochondria, infiltration of inflammatory cells, enhanced interstitial fibrosis and elevated serum creatine kinase levels. This dystrophic-like disease in STIM1 transgenic mice was abrogated by crossing in a transgene expressing a dominant negative Orai1 (dnOrai1) mutant. The dnOrai1 transgene also significantly reduced the severity of muscular dystrophy in both mdx (dystrophin mutant mice) and δ-sarcoglycan deficient mouse models of disease. Hence, Ca(2+) influx across an unstable sarcolemma due to increased activity of a STIM1-Orai1 complex is a disease determinant in muscular dystrophy, and hence, SOCE represents a potential therapeutic target.
    Human Molecular Genetics 02/2014; · 7.69 Impact Factor
  • Jeffery D Molkentin, Steven R Houser
    Circulation Research 02/2014; 114(4):e27. · 11.86 Impact Factor
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    ABSTRACT: The Ras-related guanosine triphosphatase RhoA mediates pathological cardiac hypertrophy, but also promotes cell survival and is cardioprotective after ischemia/reperfusion injury. To understand how RhoA mediates these opposing roles in the myocardium, we generated mice with a cardiomyocyte-specific deletion of RhoA. Under normal conditions, the hearts from these mice showed functional, structural, and growth parameters similar to control mice. Additionally, the hearts of the cardiomyocyte-specific, RhoA-deficient mice subjected to transverse aortic constriction (TAC)-a procedure that induces pressure overload and, if prolonged, heart failure-exhibited a similar amount of hypertrophy as those of the wild-type mice subjected to TAC. Thus, neither normal cardiac homeostasis nor the initiation of compensatory hypertrophy required RhoA in cardiomyocytes. However, in response to chronic TAC, hearts from mice with cardiomyocyte-specific deletion of RhoA showed greater dilation, with thinner ventricular walls and larger chamber dimensions, and more impaired contractile function than those from control mice subjected to chronic TAC. These effects were associated with aberrant calcium signaling, as well as decreased activity of extracellular signal-regulated kinases 1 and 2 (ERK1/2) and AKT. In addition, hearts from mice with cardiomyocyte-specific RhoA deficiency also showed less fibrosis in response to chronic TAC, with decreased transcriptional activation of genes involved in fibrosis, including myocardin response transcription factor (MRTF) and serum response factor (SRF), suggesting that the fibrotic response to stress in the heart depends on cardiomyocyte-specific RhoA signaling. Our data indicated that RhoA regulates multiple pathways in cardiomyocytes, mediating both cardioprotective (hypertrophy without dilation) and cardio-deleterious effects (fibrosis).
    Science Signaling 01/2014; 7(348):ra100. · 7.65 Impact Factor
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    ABSTRACT: The Mitochondrial Permeability Transition (MPT) pore is a voltage-sensitive unselective channel known to instigate necrotic cell death during cardiac disease. Recent models suggest that the isomerase cyclophilin D (CypD) regulates the MPT pore by binding to either the F0F1-ATP synthase lateral stalk or the mitochondrial phosphate carrier (PiC). Here we confirm that CypD, through its N-terminus, can directly bind PiC. We then generated cardiac-specific mouse strains overexpressing or with decreased levels of mitochondrial PiC to assess the functionality of such interaction. While PiC overexpression had no observable pathologic phenotype, PiC knockdown resulted in cardiac hypertrophy along with decreased ATP levels. Mitochondria isolated from hearts of these mouse lines and their respective non-transgenic controls had no divergent phenotype in terms of oxygen consumption and Ca2 +-induced MPT, as assessed by swelling and Ca2 +-retention measurements. These results provide genetic evidence indicating that the mitochondrial PiC is not a critical component of the MPT pore.
    Journal of Molecular and Cellular Cardiology 01/2014; · 5.15 Impact Factor
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    ABSTRACT: The Na(+)/K(+)ATPase (NKA) directly regulates intracellular Na(+) levels, which in turn indirectly regulates Ca(2+) levels by proximally controlling flux through the Na(+)/Ca(2+) exchanger (NCX1). Elevated Na(+) levels have been reported during heart failure, which permits some degree of reverse mode Ca(2+) entry through NCX1, as well as less efficient Ca(2+) clearance. To determine if maintaining lower intracellular Na(+) levels by NKA overexpression in the heart would enhance forward-mode Ca(2+) clearance and prevent reverse-mode Ca(2+) entry through NCX1 to protect the heart. Cardiac-specific transgenic mice overexpressing either the NKA-α1 or α2 were generated and subjected to pressure overload hypertrophic stimulation. We found that while increased expression of NKA-α1 had no protective effect, overexpression of NKA-α2 significantly decreased cardiac hypertrophy after pressure overload in mice at 2, 10 and 16 weeks of stimulation. Remarkably, total NKA protein expression and activity were not altered in either of these two transgenic models, as increased expression of one isoform led to a concomitant decrease in the other endogenous isoform. NKA-α2 overexpression, but not NKA-α1, led to significantly faster removal of bulk Ca(2+) from the cytosol in a manner requiring NCX1 activity. Mechanistically, overexpressed NKA-α2 showed greater affinity for Na(+) compared with NKA-α1, leading to more efficient clearance of this ion. Moreover, overexpression of NKA-α2, but not NKA-α1, was coupled to a decrease in phospholemman expression and phosphorylation, which would favor greater NKA activity, NCX1 activity and Ca(2+) removal. Our results suggest that the protective effect produced by increased expression of NKA-α2 on the heart after pressure overload is due to more efficient Ca(2+) clearance because this isoform of NKA preferentially enhances NCX1 activity compared with NKA-α1.
    Circulation Research 11/2013; · 11.86 Impact Factor
  • Jennifer Davis, Jeffery D Molkentin
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    ABSTRACT: Cardiac fibrosis is a substantial problem in managing multiple forms of heart disease. Fibrosis results from an unrestrained tissue repair process orchestrated predominantly by the myofibroblast. These are highly specialized cells characterized by their ability to secrete extracellular matrix (ECM) components and remodel tissue due to their contractile properties. This contractile activity of the myofibroblast is ascribed, in part, to the expression of smooth muscle α-actin (αSMA) and other tension-associated structural genes. Myofibroblasts are a newly generated cell type derived largely from residing mesenchymal cells in response to both mechanical and neurohumoral stimuli. Several cytokines, chemokines, and growth factors are induced in the injured heart, and in conjunction with elevated wall tension, specific signaling pathways and downstream effectors are mobilized to initiate myofibroblast differentiation. Here we will review the cell fates that contribute to the myofibroblast as well as nodal molecular signaling effectors that promote their differentiation and activity. We will discuss canonical versus non-canonical transforming growth factor-β (TGFβ), angiotensin II (AngII), endothelin-1 (ET-1), serum response factor (SRF), transient receptor potential (TRP) channels, mitogen-activated protein kinases (MAPKs) and mechanical signaling pathways that are required for myofibroblast transformation and fibrotic disease. This article is part of a Special Issue entitled 'Cardiac Fibroblast Review'.
    Journal of Molecular and Cellular Cardiology 11/2013; · 5.15 Impact Factor
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    ABSTRACT: During embryonic heart development, the transcription factors Tcf21, Wt1, and Tbx18 regulate activation and differentiation of epicardium-derived cells, including fibroblast lineages. Expression of these epicardial progenitor factors and localization of cardiac fibrosis was examined in mouse models of cardiovascular disease and in human diseased hearts. Following ischemic injury in mice, epicardial fibrosis is apparent in the thickened layer of subepicardial cells that express Wt1, Tbx18, and Tcf21. Perivascular fibrosis with predominant expression of Tcf21, but not Wt1 or Tbx18, occurs in mouse models of pressure overload or hypertensive heart disease, but not following ischemic injury. Areas of interstitial fibrosis in ischemic and hypertensive hearts actively express Tcf21, Wt1, and Tbx18. In all areas of fibrosis, cells that express epicardial progenitor factors are distinct from CD45-positive immune cells. In human diseased hearts, differential expression of Tcf21, Wt1, and Tbx18 also is detected with epicardial, perivascular, and interstitial fibroses, indicating conservation of reactivated developmental mechanisms in cardiac fibrosis in mice and humans. 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.
    Journal of Molecular and Cellular Cardiology 10/2013; · 5.15 Impact Factor

Publication Stats

21k Citations
3,062.20 Total Impact Points


  • 2009–2014
    • Howard Hughes Medical Institute
      Ashburn, Virginia, United States
    • Duke University
      Durham, North Carolina, United States
    • Indiana University-Purdue University School of Medicine
      • Wells Center for Pediatric Research
      Indianapolis, Indiana, United States
    • Washington University in St. Louis
      • Center for Pharmacogenomics
      Saint Louis, MO, United States
  • 2000–2014
    • University of Cincinnati
      • Department of Pediatrics
      Cincinnati, Ohio, United States
    • The Scripps Research Institute
      • Department of Molecular and Experimental Medicine
      La Jolla, California, United States
  • 1998–2014
    • Cincinnati Children's Hospital Medical Center
      • • Division of Molecular Cardiovascular Biology
      • • Department of Pediatrics
      Cincinnati, Ohio, United States
  • 2008–2013
    • Temple University
      • • Department of Physiology
      • • Independence Blue Cross Cardiovascular Research Center (CVRC)
      Philadelphia, Pennsylvania, United States
  • 2006–2012
    • University of Washington Seattle
      • Department of Physiology and Biophysics
      Seattle, WA, United States
  • 2011
    • Shanghai Jiao Tong University
      Shanghai, Shanghai Shi, China
    • Loyola University Chicago
      • Department of Cell and Molecular Physiology
      Chicago, IL, United States
  • 2010
    • Albert Einstein College of Medicine
      New York City, New York, United States
  • 2009–2010
    • University of Bristol
      • School of Physiology and Pharmacology
      Bristol, ENG, United Kingdom
  • 2007
    • Albany Medical College
      • Center for Immunology and Microbial Disease
      Albany, New York, United States
  • 2002–2007
    • University of Toronto
      • • Heart and Stroke/Richard Lewar Centre of Excellencein Cardiovascular Research
      • • Division of Cardiology
      Toronto, Ontario, Canada
  • 2002–2006
    • Hannover Medical School
      • Department of Cardiology and Angiology
      Hannover, Lower Saxony, Germany
  • 2004
    • University of Freiburg
      Freiburg, Baden-Württemberg, Germany
    • Boston University
      • Department of Medicine
      Boston, MA, United States
  • 2003
    • Tufts University
      • Molecular Cardiology Research Institute (MCRI)
      Medford, MA, United States
  • 2001
    • Massachusetts General Hospital
      • Division of Cardiology
      Boston, MA, United States
  • 1996–2000
    • University of Texas Southwestern Medical Center
      • Department of Molecular Biology
      Dallas, TX, United States
    • University of Texas MD Anderson Cancer Center
      • Department of Biochemistry and Molecular Biology
      Houston, TX, United States
    • University of Texas at Dallas
      Richardson, Texas, United States
  • 1994
    • Medical College of Wisconsin
      • Department of Physiology
      Milwaukee, WI, United States