Laboratory Papers from 2000 to Present
Millay DP, Sargent MA, Osinska H, Barton ER, Vaugniaux G, Sweeney HL, Robbins J, Molkentin JD. Genetic and pharmacologic inhibition of mitochondrial-dependent necrosis attenuates muscular dystrophy. Nat. Med. 14:442-447. 2008.
Houser SR, Molkentin JD. Does contractile Ca2+ control calcineurin-NFAT signaling and pathological hypertrophy in cardiac myocytes? Science Signal. 1(25):pe31. 2008.
Taigen T, De Windt LJ, Lim HW, Molkentin JD. Targeted inhibition of calcineurin prevents agonist-induced cardiomyocyte hypertrophy. Proc. Natl. Acad. Sci. USA. 97:1196-1201, 2000.
De Windt LJ, Lim HW, Taigen T, Wencker D, Condorelli G, Dorn GW II, Kitsis RN, Molkentin JD. Calcineurin mediated hypertrophy protects cardiomyocytes from apoptosis in vitro and in vivo: An apoptosis independent model of dilated heart failure. Circ. Res. 86:255-263, 2000.
Lim HW, Mante J, Kimball TR, Witt SA, Sussman MA, Molkentin JD. Reversal of cardiac hypertrophy in transgenic disease models by calcineurin inhibition. J. Mol. Cell. Cardiol. 32:697-709, 2000.
Sussman MA, Welch S, Walker A, Klevitsky R, Hewett TE, Witt SA, Kimball TR, Price RL, Lim HW and Molkentin JD. Hypertrohic defect unmasked by calcineurin expression in Asymptomatic Tropomodulin Overexpressing Transgenic mice. Cardiovascular Res. 46:90-101, 2000.
De Windt LJ, Lim HW, Haq S, Force T, Molkentin JD. Calcineurin promotes protein kinase C and c-Jun NH2-terminal kinase activation in the heart: Evidence of crosstalk between cardiac hypertrophic signaling pathways. J. Biol. Chem. 275:13571-13579, 2000.
Lim HW, De Windt LJ, Steinberg L, Taigen T, Witt SA, Kimball TR, Molkentin JD. Calcineurin expression, activation, and function in cardiac pressure overload hypertrophy. Circulation. 101:2431-2437, 2000.
Molkentin JD, Tymitz KM, Richardson JA, Olson EN. Abnormalities of the Genitourinary tract in female mice lacking GATA5. Mol. Cell. Biol. 20:5256-5260, 2000.
Delling U, Tureckova J, Lim HW, De Windt LJ, Rotwein P, Molkentin JD. A calcineurin/NFATc3-dependent pathway regulates skeletal muscle differentiation and slow myosin heavy chain expression. Mol. Cell. Biol. 20:6600-6611, 2000.
Delling U, Sussman MA, Molkentin JD. Re-evaluating sarcoplasmic reticulum function in heart failure. Nat. Med. 6:942-943, 2000.
Molkentin JD. Calcineurin and Beyond: Cardiac Hypertrophyc Signaling. Circ. Res. 87:731-738, 2000.
Bueno OF, De Windt LJ, Tymitz KM, Witt SA, Kimball TR, Klevitsky R, Hewett TE, Jones SP, Lefer DJ, Peng C-F, Kitsis RN, Molkentin JD. The MEK1 - ERK1/2 signaling pathway promotes compensated cardiac hypertrophy in transgenic mice. EMBO J. 19:6341-6350, 2000.
Molkentin JD. The zinc finger-containing transcription factors GATA-4, -5, and 06: ubiquitously expressed regulators of tissue-specific gene expression. J. Biol. Chem. 275:38949-38952, 2000.
Han J, Molkentin JD. Regulation of MEF2 by p38 MAPK and its implication in cardiomyocyte biology. Trends Cardiovasc. Med 10:19-22, 2000.
Bueno OF, De Windt LJ, Lim HW, Tymitz KM, Witt SA, Kimball TR, Molkentin JD. The dual-specificity phosphatase MKP-1 limits the cardiac hypertrophic response in vitro and in vivo. Circ. Res. 88:88-96, 2001.
De Windt LJ, Lim HW, Bueno OF, Liang Q, Delling U, Braz JC, Glascock BJ, Kimball TF, del Monte F, Hajjar RJ, Molkentin JD. Targeted inhibition of calcineurin attenuates cardiac hypertrophy in vivo. Proc. Natl. Acad. Sci. USA. 98:3322-3327, 2001.
Yatani A, Honda R, Tymitz KM, Lalli MJ, Molkentin JD. Enhanced Ca2+ channel currents in cardiac hypertrophy induced by activation of calcineurin-dependent pathway. J. Mol Cell. Cardiol. 33:249-259, 2001.
Haq S, Choukroun G, Lim HW, Tymitz KM, del Monte F, Gwathmey JK, Grazette L, Michael A, Hajjar RJ, Force T, Molkentin JD. Differential activation of signal transduction pathways in human hearts with hypertrophy versus advanced heart failure. Circulation. 103:670-677, 2001.
Molkentin JD, Dorn GW II. Cytoplasmic signaling pathways that regulate cardiac hypertrophy. Ann Rev. of Physiol. 63:391-426, 2001.
Lim HW, New L, Han J, Molkentin JD. Calcineurin enhances MKP-1 expression and p38 MAPK inactivation in cardiac myocytes. J. Biol. Chem. 276:15913-15919, 2001.
Sohal DS, Nghiem M, Crackower MA, Witt SA, Kimball TR, Penninger JM, Molkentin JD. Temporally-regulated and tissue-specific gene manipulations in the adult and embryonic heart using a tamoxifen-inducible Cre protein. Circ. Res. 89:20-25, 2001.
Molkentin JD. Calcineurin, mitochondrial membrane potential, and cardiomyocyte apoptosis. Circ. Res. 88:1220-1222, 2001.
Liang Q, De Windt LJ, Witt SA, Kimball TR, Markham BE, Molkentin JD. The transcription factors GATA4 and GATA6 regulate cardiomyocyte hypertrophy in vitro and in vivo. J. Biol. Chem. 276:30245-30253, 2001.
Liang Q, Wiese RJ, Bueno OF, Sai Y-S, Markham BE, Molkentin JD. The transcription factor GATA4 is activated by ERK1/2-mediated phosphorylation of serine 105 in cardiomyocytes. Mol. Cell. Biol. 21:7460-7469, 2001.
Braz JC, Bueno OF, De Windt LJ, Molkentin JD. Protein kinase Calpha (PKCalpha) regulates the hypertrophic growth of cardiomyocytes through extracellular signal-regulated kinase1/2(ERK1/2). J. Cell Biol. 156:905-919, 2002.
Bueno OF, Wilkins BJ, Tymitz KM, Glascock BJ, Kimball TF, Lorenz JN, Molkentin JD. Impaired cardiac hypertrophic response in calcineurin Aβ-deficient mice. Proc. Natl. Acad. Sci. USA. 99:4586-4591, 2002.
Wilkins BJ, Molkentin JD. Calcineurin and cardiac hypertrophy: Where have we been? Where are we going? J. Physiol. (London). 541:1-8, 2002.
Liang Q, Molkentin JD. Divergent signaling pathways converge on GATA4 to regulate cardiac hypertrophic gene expression. J. Mol Cell. Cardiol. 34:611-616, 2002.
Dai YS, Cserjesi P, Markham BE, Molkentin JD. The transcription factors GATA4 and dHAND physically interact to synergistically activate cardiac gene expression through a p300-dependent mechanism. J. Biol. Chem. 77:24390-24398, 2002.
Bueno OF, Brandt EB, Rothenberg ME, Molkentin JD. Defective T-cell development and function in calcineurin Abeta deficient mice. Proc. Natl. Acad. Sci. USA 99:9398-9403, 2002.
Wilkins BJ, De Windt LJ, Bueno OF, Braz JC, Glascock BJ, Kimball TF, Molkentin JD. Targeted disruption of NFATc3, but not NFATc4 reveals an intrinsic defect in calcineurin-mediated cardiac hypertrophic growth. Mol. Cell. Biol. 22:7603-7613. 2002.
Bueno OF, Molkentin JD. Involvement of extracellular signal-regulated kinases 1/2 (ERK1/2) in cardiac hypertrophy and cell death. Circ. Res. 91:776-781. 2002.
Molkentin JD. A friend within the heart: Natriuretic peptide receptor signaling. J. Clin. Invest. 111:1275-1277. 2003.
Parsons S, Wilkins BJ, Bueno OF, Molkentin JD. Altered skeletal muscle phenotypes in calcineurin A and Aβ gene targeted mice. Mol. Cell. Biol. 23:4331-4343. 2003.
Braz JC, Bueno OF, Liang Q, Wilkins BJ, Dai Y-S, Braunwart J, Glascock BJ, Klevitsky R, Kimball TF, Hewett TE, Molkentin JD. Targeted inhibition of p38 MAPK promotes hypertrophic cardiomyopathy through upregulation of calcineurin-NFAT signaling. J. Clin Invest. 111:1475-1486. 2003
Liang Q, Bueno OF, Wilkins BJ, Jones F, Kimball TF, Kuan C-Y, Xia Y, Molkentin JD. C-Jun NH2-terminal kinases (JNK) antagonizes adaptive cardiac growth through cross-talk with the calcineurin-NFAT signaling pathway. EMBO J. 22:5079-5089. 2003
Liang Q, Molkentin JD. Redefining the roles of p38 and JNK signaling in cardiac hypertrophy: dichotomy between cultured myocytes and animal models. J. Mol. Cell. Cardiol. 35:1385-1394. 2003
Bueno OF, Lips DJ, Kaiser RA, Wilkins BJ, Dai Y-S, Glascock BJ, Klevitsky R, Hewett TE, Kimball TR, Aronow BJ, Doevendans PA, Molkentin JD. Calcineurin Aβ gene targeting predisposes the myocardium to acute ischemia-induced apoptosis and dysfunction. Circ. Res. 94:91-99. 2004
Wilkins BJ, Dai Y-S, Bueno OF, Parsons SA, Xu J, Plank DM, Jones F, Kimball TR, Molkentin JD. Calcineurin/NFAT coupling participates in pathologic, but not physiologic cardiac hypertrophy. Circ. Res. 94:110-118. 2004
Purcell NH, Darwis D, Bueno OF, Muller JM, Schule R, Molkentin JD. Extracellular signal-regulated kinase 2 (ERK2) interacts with and is negatively regulated by the LIM-only protein FHL2 in cardiomyocytes. Mol. Cell. Biol. 24:1081-1095. 2004
Dorn GW, Molkentin JD. Manipulating cardiac contractility in heart failure: Data from mice and men. Circulation. 109:150-158. 2004
Braz JC, Gregory K, Pathak A, Zhao W, Sahin B, Klevitsky R, Kimball1 TF, Lorenz JN, Nairn AC, Liggett SB, Iodi B, Wang S, Schwartz A, Lakatta EG, DePaoli-Roach AA, Robbins J, Hewett TE, Bibb JA, Westfall MV, Kranias EG, Molkentin JD. PKCalpha regulates cardiac contractility and propensity towards heart failure. Nat. Med. 10:248-254 2004.
Kaiser RA, Bueno OF, Lips DJ, Doevendans PA, Kimball TF, Molkentin JD. Targeted Inhibition of p38 MAPK Antagonizes Cardiac Injury and Cell Death Following Ischemia-Reperfusion in vivo. J. Biol. Chem. 279:15524-15530. 2004
Lips DJ, Bueno OF, Wilkins BJ, Purcell NH, Kaiser RA, Lorenz JN, Voisin L, Saba-El-Leil MK, Meloche S, Pouyssegur J, Pages G, De Windt LJ, Doevendans PA, Molkentin JD. The MEK1-ERK2 signaling pathway protects the myocardium from ischemic injury in vivo. Circulation. 109:1938-1941. 2004
Parsons SA, Millay DP, Wilkins BJ, Bueno OF, Tsika GL, Neilson JR, Liberatore CM, Yutzey KE, Crabtree GR, Tsika RW, and Molkentin JD. Genetic loss of calcineurin blocks mechanical overload-induced skeletal muscle fiber-type switching, but not hypertrophy. J. Biol. Chem. 279:26192-26200. 2004
Sanna B, Bueno OF, Dai Y-S, Wilkins BJ, Molkentin JD. Direct and indirect interactions between calcineurin-NFAT and MEK1-ERK1/2 signaling pathways regulate gene expression and cellular growth. Mol. Cell. Biol. 25:865-878. 2005
Baines CP, Kaiser RA, Purcell NH, Blair NS, Osinska H, Hambleton MA, Brunskill EW, Sayen MR, Gottlieb RA, Dorn GW, Robbins J, and Molkentin JD. Loss of cyclophilin D reveals a critical role for mitochondrial permeability transition in cell death. Nature 434:658-662 2005.
Oka T, Dai Y-S, Molkentin JD. Regulation of calcineurin through transcriptional induction of the calcineurin Abeta promoter in vitro and in vivo. Mol. Cell. Biol. 25:6649-6659. 2005.
Kaiser RA, Liang Q, Bueno OF, Huang Y, Lackey T, Klevitsky R, Hewett TE, Molkentin JD. Genetic inhibition or activation of JNK1/2 each protects the myocardium from ischemia-reperfusion-induced cell death in vivo. J. Biol. Chem. 280:32602-32608. 2005.
Kaiser RA, Lyons JM, Duffy JY, Wagner CJ, McLean KM, O'Neill TP, Pearl JM, Molkentin JD. Inhibition of p38 reduces myocardial infarction injury in the mouse but not pig following ischemia-reperfusion. Am. J. Physiol. Heart Circ. Physiol. 289:H2747-H2751. 2005.
Dai Y-S, Xu J, Molkentin JD. The DnaJ-related factor Mrj interacts with nuclear factor of activated T cells (NFAT) and mediates transcriptional repression through class II histone deacetylase (HDAC) recruitment. Mol. Cell. Biol. 25:9936-9948. 2005.
Xu J, Kimball TR, Lorenz JN, Brown DA, Bauskin AR, Klevitsky R, Hewett TE, Breit SN. Molkentin JD. GDF-15 functions as a protective and anti-hypertrophic factor released from the myocardium in association with SMAD activation. Circ. Res. 98:342-350. 2006.
Molkentin JD. Dichotomy of calcium in the heart: contraction versus intracellular signaling. J. Clin. Invest. 116:623-626. 2006.
Xu J, Gong NL, Bodi I, Aronow BJ, Backx PH, Molkentin JD. MEF2A and MEF2C induce dilated cardiomyopathy in transgenic mice. J. Biol. Chem. 281:9152-9162. 2006.
Liu Q, Wilkins BJ, Lee YJ, Ichijo H, Molkentin JD. Direct interaction and reciprocal regulation between ASK1 and calcineurin-NFAT controls cardiomyocyte death and growth. Mol. Cell. Biol. 26:3785-3797. 2006.
Parsons SA, Millay DP, Sargent MA, McNally EM, Molkentin JD. Age-dependent effect of myostatin blockade on disease severity in a murine model of limb-girdle muscular dystrophy. Am. J. Path. 168:1975-1985. 2006.
Oka T, Maillet M, Watt AJ, Schwartz RJ, Aronow BJ, Duncan SA, Molkentin JD. Cardiac-specific deletion of Gata4 reveals its requirement for hypertrophy, compensation, and myocyte viability. Circ. Res. 98:837-845. 2006.
Sanna B, Brandt EB, Kaiser RA, Pfluger P, Witt SA, Kimball TR, van Rooij E, De Windt LJ, Rothenberg ME, Tschop MH, Benoit SC, Molkentin JD. Modulatory calcineurin interacting proteins 1 and 2 function as calcineurin facilitators in vivo. Proc. Natl. Acad. Sci. USA. 103:7327-7332. 2006.
Hambleton M, Hahn H, Pleger ST, Kuhn MC, Klevitsky R, Carr AN, Kimball TF, Hewett TE, Dorn GW, Koch WJ, Molkentin JD. Pharmacologic and genetherapeutic based inhibition of PKCa/b enhances cardiac contractility and attenuates heart failure. Circulation. 114:574-582. 2006.
Heineke J, Molkentin JD. Regulation of cardiac hypertrophy by intracellular signaling pathways. Nat. Rev. Mol. Cell. Biol. 7:589-600. 2006.
Oka T, Xu J, Molkentin JD. Re-employment of developmental transcription factors in adult heart disease. Semin. Cell. Dev. Biol. 18:117-131. 2007.
Parsons SA, Millay DP, Sargent MA, Naya FJ, McNally EM, Sweeney HL, Molkentin JD. Genetic disruption of calcineurin improves skeletal muscle pathology and cardiac disease in a mouse model of limb-girdle muscular dystrophy. J. Biol. Chem. 282:10068-10078. 2007.
Purcell NH, Wilkins BJ, York A, Saba-El-Leil MK, Meloche S, Robbins J, Molkentin JD. Genetic inhibition of cardiac ERK1/2 promotes stress-induced apoptosis and heart failure, but has no effect on hypertrophy in vivo. Proc Natl Acad Sci USA. 104:14074-14079. 2007.
Nakayama H, Chen X, Baines CP, Klevitsky R, Zhang X, Jaleel N, Chua BHL, Hewett TE, Robbins J, Houser SR, Molkentin JD. Calcium and mitochondrial-dependent cardiomyocyte necrosis as a primary mediator of heart failure. J. Clin. Invest. 117:2431-2444. 2007.
Oka T, Xu J, Kaiser RA, Melendez J, Hambleton M, Sargent MA, Lorts A, Brunskill EW, Dorn GW 2nd, Conway SJ, Aronow BJ, Robbins J, Molkentin JD. Genetic Manipulation of Periostin Expression Reveals a Role in Cardiac Hypertrophy and Ventricular Remodeling. Circ Res. 101:313-321. 2007.
Heineke J, Auger-Messier M, Xu J, Oka T, Sargetn MA, York A, Klevitsky R, Vaikunth S, Duncan SA, Aronow BJ, Robbins J, Crombleholme TM, Molkentin JD. Cardiomyocyte GATA4 functions as a stress-responsive regulator of angiogenesis in the heart. J. Clin. Invest. 117:3198-3210. 2007.
Hambleton M, York A, Sargent MA, Kaiser RA, Lorenz JN, Robbins J, Molkentin JD. Inducible and myocyte-specific inhibition of PKCa enhances cardiac contractility and protects against infarction-induced heart failure. Am. J. Physiol. Heart Circ. Phys. 293:H3768-H3771. 2007.
