Jeffery D Molkentin


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


  1. Molkentin J, Bugg D, Ghearing N, Dorn L, Kim P, Sargent M, et al. Fibroblast-Specific Genetic Manipulation of p38 Mitogen-Activated Protein Kinase In Vivo Reveals Its Central Regulatory Role in Fibrosis. Circulation. 2017;136:549-561 pubmed publisher
  2. Cai C, Molkentin J. The Elusive Progenitor Cell in Cardiac Regeneration: Slip Slidin' Away. Circ Res. 2017;120:400-406 pubmed publisher
    ..This review will weigh the emerging evidence, suggesting that the adult mammalian heart lacks a definable myocyte-generating progenitor cell of biological significance. ..
  3. Correll R, Grimes K, Prasad V, Lynch J, Khalil H, Molkentin J. Overlapping and differential functions of ATF6α versus ATF6β in the mouse heart. Sci Rep. 2019;9:2059 pubmed publisher
    ..This work reveals previously unappreciated roles for ATF6α and ATF6β in regulating the pressure overload induced cardiac hypertrophic response and in controlling the expression of genes that condition the ER during hemodynamic stress. ..
  4. Schips T, Vanhoutte D, Vo A, Correll R, Brody M, Khalil H, et al. Thrombospondin-3 augments injury-induced cardiomyopathy by intracellular integrin inhibition and sarcolemmal instability. Nat Commun. 2019;10:76 pubmed publisher
    ..Thus, Thbs proteins mediate the intracellular processing of integrin plasma membrane attachment complexes to regulate the dynamics of cellular remodeling and membrane stability. ..
  5. Molkentin J. Parsing good versus bad signaling pathways in the heart: role of calcineurin-nuclear factor of activated T-cells. Circ Res. 2013;113:16-9 pubmed publisher
    ..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. ..
  6. Kanisicak O, Vagnozzi R, Molkentin J. Identity Crisis for Regenerative Cardiac cKit+ Cells. Circ Res. 2017;121:1130-1132 pubmed publisher
  7. Khalil H, Maillet M, Molkentin J. Spatial Gene Profiling in the Ischemic Heart: Fibroblasts Put on Their SOX. Circulation. 2017;136:1410-1411 pubmed publisher
  8. Vagnozzi R, Sargent M, Lin S, Palpant N, Murry C, Molkentin J. Genetic Lineage Tracing of Sca-1+ Cells Reveals Endothelial but Not Myogenic Contribution to the Murine Heart. Circulation. 2018;: pubmed publisher
  9. Vagnozzi R, Molkentin J, Houser S. New Myocyte Formation in the Adult Heart: Endogenous Sources and Therapeutic Implications. Circ Res. 2018;123:159-176 pubmed publisher
    ..Hence, future therapeutic approaches should take into consideration the fundamental biology of myocyte renewal in designing strategies to potentially replenish these cells in the injured heart. ..

More Information


  1. Brody M, Vanhoutte D, Schips T, Boyer J, Bakshi C, Sargent M, et al. Defective Flux of Thrombospondin-4 through the Secretory Pathway Impairs Cardiomyocyte Membrane Stability and Causes Cardiomyopathy. Mol Cell Biol. 2018;38: pubmed publisher
    ..These results suggest that transit through the secretory pathway is required for Thbs4 to augment sarcolemmal stability, while ER stress induction and vesicular expansion mediated by Thbs4 are exclusively intracellular processes. ..
  2. Kwong J, Molkentin J. Physiological and pathological roles of the mitochondrial permeability transition pore in the heart. Cell Metab. 2015;21:206-14 pubmed publisher
    ..A better understanding of MPTP structure and function will likely suggest novel cardioprotective therapeutic approaches. ..
  3. Accornero F, van Berlo J, Correll R, Elrod J, Sargent M, York A, et al. Genetic Analysis of Connective Tissue Growth Factor as an Effector of Transforming Growth Factor β Signaling and Cardiac Remodeling. Mol Cell Biol. 2015;35:2154-64 pubmed publisher
  4. Maliken B, Kanisicak O, Karch J, Khalil H, Fu X, Boyer J, et al. Gata4-Dependent Differentiation of c-Kit+ Derived Endothelial Cells Underlies Artefactual Cardiomyocyte Regeneration in the Heart. Circulation. 2018;: pubmed publisher
    ..Deletion of Gata4 from c-Kit+ endothelial progenitor cells or adult endothelial cells negatively impacted angiogenesis and capillary network integrity. ..
  5. Schwanekamp J, Lorts A, Vagnozzi R, Vanhoutte D, Molkentin J. Deletion of Periostin Protects Against Atherosclerosis in Mice by Altering Inflammation and Extracellular Matrix Remodeling. Arterioscler Thromb Vasc Biol. 2016;36:60-8 pubmed publisher
    ..The data suggest that periostin could be a therapeutic target for atherosclerotic plaque formation through modulation of the immune response and extracellular matrix remodeling. ..
  6. Karch J, Molkentin J. Regulated necrotic cell death: the passive aggressive side of Bax and Bak. Circ Res. 2015;116:1800-9 pubmed publisher
    ..We will also discuss how these Bcl-2 family member effectors could be part of a larger integrated network that ultimately decides the fate of a given cell somewhere within a molecular continuum between apoptosis and regulated necrosis. ..
  7. Goonasekera S, Davis J, Kwong J, Accornero F, Wei LaPierre L, Sargent M, et al. Enhanced Ca²? influx from STIM1-Orai1 induces muscle pathology in mouse models of muscular dystrophy. Hum Mol Genet. 2014;23:3706-15 pubmed publisher
    ..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. ..
  8. Kwong J, Lu X, Correll R, Schwanekamp J, Vagnozzi R, Sargent M, et al. The Mitochondrial Calcium Uniporter Selectively Matches Metabolic Output to Acute Contractile Stress in the Heart. Cell Rep. 2015;12:15-22 pubmed publisher
    ..Hence, MCU is a dedicated regulator of short-term mitochondrial Ca(2+) loading underlying a "fight-or-flight" response that acutely matches cardiac workload with ATP production. ..
  9. Liu R, van Berlo J, York A, Vagnozzi R, Maillet M, Molkentin J. DUSP8 Regulates Cardiac Ventricular Remodeling by Altering ERK1/2 Signaling. Circ Res. 2016;119:249-60 pubmed publisher
  10. Correll R, Lynch J, Schips T, Prasad V, York A, Sargent M, et al. Mitsugumin 29 regulates t-tubule architecture in the failing heart. Sci Rep. 2017;7:5328 pubmed publisher
    ..Moreover, preservation of t-tubule structure by Mg29 induction significantly increases the function of the failing heart. ..
  11. Tjondrokoesoemo A, Schips T, Sargent M, Vanhoutte D, Kanisicak O, Prasad V, et al. Cathepsin S Contributes to the Pathogenesis of Muscular Dystrophy in Mice. J Biol Chem. 2016;291:9920-8 pubmed publisher
    ..Hence, Ctss induction during muscular dystrophy is a pathologic event that partially underlies disease pathogenesis, and its inhibition might serve as a new therapeutic strategy in DMD. ..
  12. Accornero F, Schips T, Petrosino J, Gu S, Kanisicak O, van Berlo J, et al. BEX1 is an RNA-dependent mediator of cardiomyopathy. Nat Commun. 2017;8:1875 pubmed publisher
    ..Thus, BEX1 functions as an mRNA-dependent effector that augments pathology-promoting gene expression during heart failure. ..
  13. Brody M, Schips T, Vanhoutte D, Kanisicak O, Karch J, Maliken B, et al. Dissection of Thrombospondin-4 Domains Involved in Intracellular Adaptive Endoplasmic Reticulum Stress-Responsive Signaling. Mol Cell Biol. 2016;36:2-12 pubmed publisher
    ..Finally, deletion of Atf6α abrogated Thbs4-induced vesicular expansion. Taken together, these data identify the critical intracellular functional domains of Thbs4, which was formerly thought to have only extracellular functions. ..
  14. Liu R, Correll R, Davis J, Vagnozzi R, York A, Sargent M, et al. Cardiac-specific deletion of protein phosphatase 1β promotes increased myofilament protein phosphorylation and contractile alterations. J Mol Cell Cardiol. 2015;87:204-13 pubmed publisher
    ..These results suggest a unique functional role for the PP1β isoform in affecting cardiac contractile function. ..
  15. Accornero F, Kanisicak O, Tjondrokoesoemo A, Attia A, McNally E, Molkentin J. Myofiber-specific inhibition of TGF? signaling protects skeletal muscle from injury and dystrophic disease in mice. Hum Mol Genet. 2014;23:6903-15 pubmed publisher
    ..Hence, our results show that the myofibers are central mediators of the deleterious effects associated with TGF? signaling in MD. ..
  16. Wissing E, Boyer J, Kwong J, Sargent M, Karch J, McNally E, et al. P38? MAPK underlies muscular dystrophy and myofiber death through a Bax-dependent mechanism. Hum Mol Genet. 2014;23:5452-63 pubmed publisher
    ..Moreover, use of a p38 MAPK pharmacologic inhibitor reduced dystrophic disease in Sgcd(-/-) mice suggesting a future therapeutic approach to delay disease. ..
  17. Liu R, Molkentin J. Regulation of cardiac hypertrophy and remodeling through the dual-specificity MAPK phosphatases (DUSPs). J Mol Cell Cardiol. 2016;101:44-49 pubmed publisher
    ..This review summarizes recent literature on the physiological and pathological roles of MAPK-specific DUSPs in regulating MAPK signaling in the heart and the effect on cardiac growth and remodeling. ..
  18. Davis J, Davis L, Correll R, Makarewich C, Schwanekamp J, Moussavi Harami F, et al. A Tension-Based Model Distinguishes Hypertrophic versus Dilated Cardiomyopathy. Cell. 2016;165:1147-1159 pubmed publisher
    ..This tension-based model also has the potential to inform pharmacologic treatment options in cardiomyopathy patients. ..
  19. Tjondrokoesoemo A, Schips T, Kanisicak O, Sargent M, Molkentin J. Genetic overexpression of Serpina3n attenuates muscular dystrophy in mice. Hum Mol Genet. 2016;25:1192-202 pubmed publisher
    ..These results suggest the use of select protease inhibitors as a strategy for treating MD. ..
  20. Correll R, Goonasekera S, van Berlo J, Burr A, Accornero F, Zhang H, et al. STIM1 elevation in the heart results in aberrant Ca²⁺ handling and cardiomyopathy. J Mol Cell Cardiol. 2015;87:38-47 pubmed publisher
    ..We conclude that STIM1 has an unexpected function in the heart where it alters communication between the sarcolemma and SR resulting in greater Ca(2+) flux and a leaky SR compartment. ..