Molkentin Lab

Accornero F, Schips TG, Petrosino JM, Gu S-Q, Kanisicak O, van Berlo JH, Molkentin JD. BEX1 is an RNA-dependent mediator of cardiomyopathy. Nat Commun. 2017.  8:1875. doi: 10.1038

Karch J, Schips TG, Maliken BD, Brody MJ, Sargent MA, Molkentin JD. Autophagic cell death is dependent on lysosomal membrane permeability through Bax and Bak. eLife, 2017. 6:10.7554.

Khalil H, Kanisicak O, Prasad V, Correll RN, Fu X, Schips T, Vagnozzi RJ, Liu R, Huynh T, Lee SJ Karch J,  Molkentin JD. Fibroblast-specific genetic dissection of TGFβ-Smad2/3 signaling in cardiac fibrosis. J. Clin. Invest. 2017,  2017;127:3770–3783

Schwanekamp JA, Lorts A, Sargent MA, York AJ, Grimes KM, Fischesser DM, Gokey JJ, Whitsett JA, Conway SJ, Molkentin JD. TGFBI functions similar to periostin but is uniquely dispensable during cardiac injury. PLoS One. 2017;12(7):e0181945.

Cai CL, Molkentin JD. The Elusive Progenitor Cell in Cardiac Regeneration: Slip Slidin' Away. Circ Res. 2017;120:400-406.

Molkentin JD*, Bugg D, Ghearing N, Dorn LE, Kim P, Sargent MA, Gunaje J, Otsu K, Davis J*. Fibroblast-specific genetic manipulation of p38 MAPK in vivo reveals its central regulatory role in fibrosis. Circulation. 2017. *co-corresponding

Correll RN, Makarewich CA, Zhang H, Zhang C, Sargent MA, York AJ, Berretta RM, Chen X, Houser SR, Molkentin JD. Caveolae-localized L-type Ca2+ channels do not contribute to function or hypertrophic signalling in the mouse heart. Cardiovasc Res. 2017 Jun 1;113(7):749-759.

Tallquist MD, Molkentin JD. Cardiac fibroblast identity and function in ventricular remodeling. Nat Rev Cardiol. 2017 Apr 24.

Correll NC, Lynch JM, Schips TG, Prasad V, York YJ, Sargent MA, Brochet DXP, Ma J, Molkentin JD. Mitsugumin 29 regulates t-tubule architecture in the failing heart. Scientific Reports. 2017.

Liu R, Khalil H, Lin SJ, Sargent MA, York AJ, Molkentin JD. Nemo-Like Kinase (NLK) Is a Pathological Signaling Effector in the Mouse Heart. PLoS One. 2016;11:e0164897.

Liu R, Molkentin JD. Regulation of cardiac hypertrophy and remodeling through the dual-specificity MAPK phosphatases (DUSPs). J Mol Cell Cardiol. 2016 2828:30318-2. 

Liu R, van Berlo JH, York AJ, Maillet M, Vagnozzi RJ, Molkentin JD. DUSP8 Regulates Cardiac Ventricular Remodeling by Altering ERK1/2 Signaling. Circ Res. 2016;119:249-260.

Vanhoutte D, Schips TG, Kwong JQ, Davis J, Tjondrokoesoemo A, Brody MJ, Sargent MA, Kanisicak O, Yi H, Gao QQ, Rabinowitz JE, Volk T, McNally EM, Molkentin JD. Thrombospondin expression in myofibers stabilizes muscle membranes. eLife. 2016 Sep 26;5.

van Berlo JH, Molkentin JD. Most of the Dust Has Settled: cKit+ Progenitor Cells Are an Irrelevant Source of Cardiac Myocytes In Vivo.  Circ Res. 2016;118:17-19.

Tjondrokoesoemo A, Schips TG, Sargent MA, Vanhoutte D, Kanisicak O, Prasad V, Lin SJ, Maillet M, Molkentin JD. Cathepsin S contributes to the pathogenesis of muscular dystrophy in mice. J Biol Chem. 2016  291:9920-9928.

Davis J,  Davis LC  Correll RN, Makarewich CA, Schwanekamp JA, Moussavi-Harami F, Wang D, York AJ, Wu H, Houser SR, Seidman CE, Seidman JG, Regnier M, Metzger JM, Wu JC, Molkentin JD. A tension based model distinguishes hypertrophic versus dilated cardiomyopathy. Cell.  2016;165:1-13.

Kanisicak O, Khalil H, Ivey M, Karch J, Maliken BD, Correll RN, Brody MJ, Lin S-H J,  Aronow BJ, Tallquist MD, Molkentin JD. Genetic lineage tracing defines myofibroblast origin and function in the injured heart. Nature Commun. 2016;7:12260.

Schwanekamp JA, Lorts A, Vagnozzi RJ, Vanhoutte D, Molkentin JD. Deletion of Periostin Protects Against Atherosclerosis in Mice by Altering Inflammation and Extracellular Matrix Remodeling. Arterioscler Thromb Vasc Biol. 2016;36:60-68.

Tjondrokoesoemo A, Schips T, Kanisicak O, Sargent MA, Molkentin JD. Genetic overexpression of Serpina3n attenuates muscular dystrophy in mice. Hum Mol Genet. 2016;25:1192-1202.

Liu R, Correll RN, Davis J, Vagnozzi RJ, York AJ, Sargent MA, Nairn AC, Molkentin JD. Cardiac-specific deletion of protein phosphatase 1? promotes increased myofilament protein phosphorylation and contractile alterations. J Mol Cell Cardiol. 2015;87:204-213.

Brody MJ, Schips TG, Vanhoutte D, Kanisicak O, Karch J, Maliken BD, Blair NS, Sargent MA, Prasad V, Molkentin JD. Dissection of thrombospondin-4 domains involved in intracellular adaptive ER Stress responsive signaling. Mol Cell Biol. 2015;36:2-12.

Davis J, Salomonis N, Ghearing N, Lin S-H J, Kwong JQ, Sargent MA, Mohan A, Swanson MS, Molkentin JD.  MBNL1-mediated regulation of differentiation RNAs promotes myofibroblast transformation and the fibrotic response. Nature Commun. 2015:16:10084.

Kwong JQ, Molkentin JD. Physiological and pathological roles of the mitochondrial permeability transition pore in the heart. Cell Metabolism. 2015 Feb 3;21(2):206-14.

Accornero F, van Berlo JH, Correll RN, Elrod JW, Sargent MA, York A, JE Rabinowitz, Leask A, Molkentin JD. Genetic analysis of CTGF as an effector of TGFb signaling and cardiac remodeling. Mol Cell Biol. 2015;35:2154-2164.

Karch J, Kanisicak O, Brody MJ, Sargent MA, Michael DM, Molkentin JD. Necroptosis interfaces with MOMP and the MPTP in mediating cell death. PLOS one. 2015;10(6):e0130520.

Karch J, Molkentin JD. Regulated Necrotic Cell Death: The Passive Aggressive Side of Bax and Bak. Circ Res. 2015;116:1800-1809.

Kwong JQ, Lu X, Correll RN, Vagnozzi RJ, Sargent MA, York AJ, Zhang J, Bers DM, Molkentin JD. The mitochondrial calcium uniporter selectively matches metabolic output to acute contractile stress in the heart. Cell Reports. 2015;12:15-22.

Burr AR, Molkentin JD. Genetic evidence in the mouse solidifies the calcium hypothesis of myofiber death in muscular dystrophy. Cell Death & Diff. 2015 Sep;22(9):1402-12.

Correll RN, Goonasekera SA, van Berlo J, Burr AR, Accornero F, York AJ, Sargent MA, Houser SR, Molkentin JD. STIM1 elevation in the heart results in aberrant Ca2+ handling and cardiomyopathy. J Mol Cell Cardiol. 2015 Aug 1;87:38-47.

Goonasekera SA, Kwong JQ, Davis J, Accornero F, Wei-LaPierre L, Sargent MA, Dirksen RT, Molkentin JD. Enhanced Ca2+ influx from STIM1-Orai1 underlies muscle pathology in mouse models of muscular dystrophy. Hum Mol Genetics. 2014;23:3706-3715

Kwong JQ, Davis J, Baines CP, Sargent MA, Karch J, Wang X, Huang T, Molkentin JD. Genetic deletion of the mitochondrial phosphate carrier desensitizes the mitochondrial permeability transition pore and causes cardiomyopathy. Cell Death & Diff. 2014;21:1209-1217

van Berlo JH, Kanisicak O, Maillet M, Vagnozzi RJ, Karch J, Lin S-CJ, Middleton RC, Marbán E, Molkentin JD. C-kit+ cells minimally contribute cardiomyocytes to the heart. Nature. 2014;509:337-341.

Davis J, Molkentin JD. Myofibroblasts: Trust your heart and let fate decide. J Mol Cell Cardiol. 2014;70C:9-18

Burr AR, Millay DP, Goonasekera SA, Park KH, Sargent MA, Collins J, Altamirano F, Philipson KD, Allen PD, Ma J, López JR, Molkentin JD.Na+ dysregulation coupled with Ca2+ entry through NCX1 promotes muscular dystrophy in mice. Mol. Cell. Biol. 2014;34:1991-2002. 

Wissing ER, Boyer JG, Kwong JQ, Sargent MA, Karch J, McNally EM, Otsu K, Molkentin JD. p38alpha MAPK underlies muscular dystrophy and myofiber death through a Bax-dependent mechanism. Hum. Mol. Genetics. 2014 Oct 15;23(20):5452-63.

Karch J, Molkentin JD. Identifying the components of the elusive mitochondrial permeability transition pore. Proc. Natl. Acad. Sci. USA. 2014 Jul 22;111(29):10396-7.

Kwong JQ, Molkentin JD. In sickness and health: role of the mitochondrial permeability transition pore in the heart. Cell Metabolism. 2014;21:206-214.

Davis J, Kwong JQ, Kitsis RN, Molkentin JD. Apoptosis Repressor with a CARD Domain (ARC) Restrains Bax-mediated Pathogenesis in Dystrophic Skeletal Muscle.PLOS One 2013: 8(12),e82053

van Berlo JH, Aronow BJ, Molkentin JD. Parsing the roles of the transcription factors GATA-4 and GATA-6 in the adult cardiac hypertrophic response.PLOS One 2013;8:e84591

Correll RN, Eder P, Burr AR, Despa S, Davis JM, Bers DM, Molkentin JD. Overexpression of the Na+/K+ ATPase α2 but not α1 Isoform Attenuates Pathological Cardiac Hypertrophy and Remodeling. Circ Res. 2013;114:249-256

van Berlo JH, Maillet M, Molkentin JD. Signaling effectors underlying pathologic growth and remodeling of the heart. J Clin Invest. 2013;123:37-45.

Auger-Messier M, Accornero F, Goonasekera SA, Bueno OF, Lorenz JN, van Berlo JH, Willette RN, Molkentin JD. Unrestrained p38 MAPK Activation in Dusp1/4 Double Null Mice Induces Cardiomyopathy. Circ Res. 2013;112:48-56.

Elrod JW, Molkentin JD. Physiologic Functions of Cyclophilin D and the Mitochondrial Permeability Transition Pore. Circ J. 2013;75:1111-1122.

Molkentin JD. Parsing good versus bad signaling pathways in the heart: role of calcineurin-nuclear factor of activated T-cells. Circ Res. 2013;113:16-19.

Karch J, Kwong JQ, Burr AR, Sargent MA, Elrod JW, Peixoto PM, Martinez-Caballero S, Osinka H, Cheng EH, Robbins J, Kinnally KW, Molkentin JD. Bax and Bak function as the outer membrane component of the mitochondrial pore in regulating necrotic cell death. eLife. 2013;2:e00772.

Molkentin JD, Houser SR. Are Resident c-Kit+ Cardiac Stem Cells Really All That Are Needed to Mend a Broken Heart?  Circ Res. 2013;113:1037-1039.

Davis J, Burr AR, Davis GF, Birnbaumer L, Molkentin JD.  A TRPC6-dependent pathway for myofibroblast transdifferentiation and wound healing in vivo.  Dev. Cell  2012. 23:705-715.

Lorts A, Schwanekamp JA, Baudino TA, McNally EM, Molkentin JD.  Deletion of periostin reduced muscular dystrophy and fibrosis in mice by modulating the transforming growth factor-b pathway.  Proc Natl Acad Sci USA.  2012. 109:10978-10983

Lynch JM, Maillet M, Vanhoutte D, Schloemer A, Sargent MA, Blair NS, Lynch KA, Okada T, Aronow BJ, Osinska H, Prywes R, Lorenz JN, Mori K, Lawler J, Robbins J, Molkentin JD. A thrombospondin-dependent pathway for a protective ER stress response.  Cell.  2012. 149,1257-1268

Liu Q, Chen Y, Auger-Messier M, Molkentin JD. Interaction Between NFkB and NFAT Coordinates Cardiac Hypertrophy and Pathological Remodeling. Circ Res. 2012. 110:1077-1086

Goonasekera SA, Molkentin JD. Unraveling the secrets of a double life: Contractile versus signaling Ca(2+) in a cardiac myocyte. J Mol Cell Cardiol. 52:317-322. 2012.

Goonasekera SA, Hammer K, Auger-Messier M, Bodi I, Chen X, Zhang H, Reiken S, Elrod JW, Correll RN, York AJ, Sargent MA, Hofmann F, Moosmang S,  Marks AR, Houser SR, Bers DM, Molkentin JD. Decreased cardiac L-type Ca²⁺ channel activity induces hypertrophy and heart failure in mice. J. Clin Invest. 2012.  122:280-290

Kehat I, Davis J, Tiburcy M, Accornero F, Saba-El-Leil M, Maillet M, York AJ, Lorenz JN, Zimmermann WH, Meloche S, Molkentin JD. Extracellular signal-regulated kinases 1 and 2 regulate the balance between eccentric and concentric cardiac growth. Circ. Res. 108:176-183. 2011.

Goonasekera SA, Lam CK, Millay DP, Sargent MA, Hajjar RJ, Kranias EG, Molkentin JD. Mitigation of muscular dystrophy in mice by SERCA overexpression in skeletal muscle. J. Clin. Invest. 121:1044-1052. 2011.

Kehat I, Accornero F, Aronow BJ, Molkentin JD. Modulation of chromatin position and gene expression by HDAC4 interaction with nucleoporins. J. Cell. Biol. 193:21-29. 2011.

Eder P, Molkentin JD. TRPC channels as effectors of cardiac hypertrophy. Circ Res. 108:265-272. 2011. 

Liu Q, Molkentin JD. Protein kinase Cα as a heart failure therapeutic target. J Mol Cell Cardiol.  51:474-478. 2011

Molkentin JD. The transcription factor C/EBPb serves as a master regulator of physiologic cardiac hypertrophy. Circ Res. 108:277-278.  2011

Kehat I, Accornero F, Aronow BJ, Molkentin JD. Modulation of chromatin position and gene expression by HDAC4 interaction with nucleoporins.  J. Cell. Biol.  193:21-29. 2011

Accornero F, van Berlo JH, Benard MJ, Lorenz JN, Carmeliet P, Molkentin JD. Placental Growth Factor Regulates Cardiac Adaptation and Hypertrophy Through a Paracrine Mechanism. Circ Res.  109:272-280.  2011

van Berlo JH, Elrod JW, Aronow BJ, Pu WT, Molkentin JD. Serine 105 phosphorylation of transcription factor GATA4 is necessary for stress-induced cardiac hypertrophy in vivo. Proc. Natl. Acad. Sci.  108:12331-12336.  2011

van Berlo JH, Elrod JW, van den Hoogenhof MM, York AJ, Aronow BJ, Duncan SA, Molkentin JD. The transcription factor GATA-6 regulates pathological cardiac hypertrophy. Circ Res. 107:1032-1040. 2010.

Elrod JW, Wong R, Mishra S, Vagnozzi RJ, Sakthievel B, Goonasekera SA, Karch J, Gabel S, Farber J, Force T, Brown JH, Murphy E, Molkentin JD.  Cyclophilin D controls mitochondrial pore-dependent Ca(2+) exchange, metabolic flexibility, and propensity for heart failure in mice. J. Clin Invest.120:3680-3687. 2010. 

Nakayama H, Bodi I, Maillet M, Desantiago J, Domeier TL, Mikoshiba K, Lorenz JN, Blatter LA, Bers DM, Molkentin JD. The IP3 receptor regulates cardiac hypertrophy in response to select stimuli. Circ Res. 107:659-666. 2010.

Wissing ER, Millay DP, Vuagniaux G, Molkentin JD. Debio-025 is more effective than prednisone in reducing muscular pathology in mdx mice. Neuromuscul Disord.  20:753-760. 2010.

Heineke J, Auger-Messier M, Correll RN, Xu J, Benard MJ, Yuan W, Drexler H, Parise LV, Molkentin JD. CIB1 is a regulator of pathological cardiac hypertrophy. Nat. Med. 16:872-879. 2010. 

Wu X, Eder P, Chang B, Molkentin JD. TRPC channels are necessary mediators of pathologic cardiac hypertrophy. Proc Natl Acad Sci USA. 107:7000-7005. 2010.

Maillet M, Davis J, Auger-Messier M, York A, Osinska H, Piquereau J, Lorenz JN, Robbins J, Ventura-Clapier R, Molkentin JD. Heart-specific deletion of CNB1 reveals multiple mechanisms whereby calcineurin regulates cardiac growth and function. J Biol Chem. 285:6716-6724. 2010.

Heineke J, Auger-Messier M, Xu J, Sargent M, York A, Welle S, Molkentin JD. Genetic deletion of myostatin from the heart prevents skeletal muscle atrophy in heart failure. Circulation. 121:419-25. 2010.

Heineke J, Wollert KC, Osinska H, Sargent MA, York AJ, Robbins J, Molkentin JD. Calcineurin protects the heart in a murine model of dilated cardiomyopathy. J Mol Cell Cardiol. 48:1080-1087. 2010.

Millay DP, Goonasekera SA, Sargent MA, Maillet M, Aronow BJ, Molkentin JD. Calcium influx is sufficient to induce muscular dystrophy through a TRPC-dependent mechanism. Proc. Natl. Acad. Sci. USA. 106:19023-19028. 2009.

Liu Q, Sargent MA, York AJ, Molkentin JD. ASK1 regulates cardiomyocyte death but not hypertrophy in transgenic mice. Circ Res. 105:1110-1117. 2009.

Nakayama H, Bodi I, Chen X, Lorenz J, Houser SR, Robbins, J, Schwartz A, Molkentin J. a1G T-type current antagonizes cardiac hypertrophy through a NOS3-dependent mechanism. J. Clin. Invest. 119:3787-3796. 2009.

Millay DP, Maillet M, Roche JA, Sargent MA, McNally EM, Bloch RJ, Molkentin JD. Genetic manipulation of dysferlin expression in skeletal muscle: Novel insights into muscular dystrophy. Am. J. Path. 175:1817-1823. 2009.

Maillet M, Lynch JM, Sanna B, York AJ, Zheng Y, Molkentin JD.  Cdc42 is an antihypertrophic molecular switch in the heart. J. Clin. Invest. 119:3079-3088. 2009.

Liu Q, Chen X, Macdonnell SM, Kranias EG, Lorenz JN, Leitges M, Houser SR, Molkentin JD. Protein kinase C{alpha}, but not PKC{beta} or PKC{gamma}, regulates contractility and heart failure susceptibility: implications for ruboxistaurin as a novel therapeutic approach. Circ. Res. 105:194-200. 2009.

Baines CP, Molkentin JD. Adenine nucleotide translocase-1 induces cardiomyocyte death through upregulation of the pro-apoptotic protein Bax. J Mol Cell Cardiol. 46:969-977. 2009.

Wu X, Chang B, Blair NS, Sargent M, York AJ, Robbins J, Shull GE, Molkentin JD.  Plasma membrane Ca2+-ATPase isoform 4 antagonizes cardiac hypertrophy in association with calcineurin inhibition in rodents. J. Clin. Invest. 119:976-985. 2009.

Lorts A, Schwanekamp JA, Elrod JW, Sargent MA, Molkentin JD. Genetic manipulation of periostin expression in the heart does not affect myocyte content, cell cycle activity, or cardiac repair. Circ Res. 104:e1-7. 2009.

Liu Q, Caldwell Busby J, Molkentin JD. Interaction between TAK1-TAB1-TAB2 and RCAN1-calcineurin defines a signaling nodal control point. Nat. Cell Biol. 11:154-161. 2009.

Maillet M, Purcell NH, Sargent MA, York A, Bueno OF, Molkentin JD. Dusp6 (MKP3) null mice show enhanced ERK1/2 phosphorylation at baseline and increased myocyte proliferation in the heart affecting disease susceptibility. J Biol Chem. 283:31246-31255. 2008.

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.

Heineke J, Auger-Messier M, Xu J, Oka T, Sargent 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 murine heart. J. Clin. Invest. 117:3198-3210. 2007.

Nakayama H, Chen X, Baines CP, Klevitsky R, Zhang X, Jaleel N, Chua BHL, Hewett TE, Robbins J, Houser SR, Molkentin JD. Ca2+- and mitochondrial-dependent cardiomyocyte necrosis as a primary mediator of heart failure. J. Clin. Invest. 117:2431-2444. 2007.

Baines CP, Kaiser RA, Sheiko T, Craigen WJ, Molkentin JD. Voltage-dependent anion channels are dispensable for mitochondrial-dependent cell death. Nat. Cell Biol. 9:550-555. 2007.

Baines CP, Kaiser RA, Purcell NH, Blair NS, Osinska H, Hambleton MA, Brunskill EW, Sayen MR, Gottlieb RA, Dorn GW, Robbins J, Molkentin JD. Loss of cyclophilin D reveals a critical role for mitochondrial permeability transition in cell death. Nature. 434:658-662. 2005.

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. PKC-alpha regulates cardiac contractility and propensity towards heart failure. Nat. Med. 10:248-254. 2004.