Joseph Metzger, Ph.D.

Professor and Chair, Dept. of Integrative Biology and Physiology

E-MAIL: metzgerj@umn.edu

Research Interests:

Joseph M. Metzger is Professor and Chair of Integrative Biology and Physiology at the University of Minnesota 's School of Medicine . He holds the Maurice B. Visscher Endowed Chair in Physiology.

The Metzger lab is a dynamic and interactive research group that spans from graduate students to postdoctoral and clinical fellows, and includes undergraduates, visiting professors and research associates. Lab expertise ranges from physiologists, virologists, bioengineers, cardiologists, surgeons, and molecular and cellular biologists. The lab welcomes new investigators from diverse academic backgrounds who share the ultimate goal of translating basic science insights into potential clinical therapies for inherited muscle diseases. The lab features genetic engineering of muscle cells and utilizes state-of-the-art viral vector systems for experimental genetic therapeutics directed at remediation of neuromuscular and cardiovascular disorders. The Metzger lab recently developed a Molecular band-aid for muscle defects of Duchenne Muscular Dystrophy, and Metzger serves as chair of the scientific advisory board of Phrixus Inc. a biotech company pursuing this technology for application in human patients.

Selected Publications:

(For a comprehensive list of recent publications, refer to PubMed, a service provided by the National Library of Medicine.)

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 May 19;165(5):1147-59.

Asp ML, Sjaastad FV, Siddiqui JK, Davis JP, Metzger JM. Effects of Modified Parvalbumin EF-Hand Motifs on Cardiac Myocyte Contractile Function. Biophys J. 2016 May 10;110(9):2094-105.

Heinis FI, Vermillion KL, Andrews MT, Metzger JM. Myocardial performance and adaptive energy pathways in a torpid mammalian hibernator. Am J Physiol Regul Integr Comp Physiol. 2015 Aug 15;309(4):R368-77.

Cui W, Jang A, Zhang P, Thompson B, Townsend D, Metzger JM, Zhang J. Early Detection of Myocardial Bioenergetic Deficits: A 9.4 Tesla Complete Non Invasive 31P MR Spectroscopy Study in Mice with Muscular Dystrophy. PLoS One. 2015 Aug 11;10(8):e0135000.

Barnabei MS, Sjaastad FV, Townsend D, Bedada FB, Metzger JM. Severe dystrophic cardiomyopathy caused by the enteroviral protease 2A-mediated C-terminal dystrophin cleavage fragment. Sci Transl Med. 2015 Jul 1;7(294):294ra106.

McNally EM, Kaltman JR, Benson DW, Canter CE, Cripe LH, Duan D, Finder JD, Groh WJ, Hoffman EP, Judge DP, Kertesz N, Kinnett K, Kirsch R, Metzger JM, Pearson GD, Rafael-Fortney JA, Raman SV, Spurney CF, Targum SL, Wagner KR, Markham LW; Working Group of the National Heart, Lung, and Blood Institute; Parent Project Muscular Dystrophy. Contemporary cardiac issues in Duchenne muscular dystrophy. Working Group of the National Heart, Lung, and Blood Institute in collaboration with Parent Project Muscular Dystrophy. Circulation. 2015 May 5;131(18):1590-8.

Bartos JA, Matsuura TR, Sarraf M, Youngquist ST, McKnite SH, Rees JN, Sloper DT, Bates FS, Segal N, Debaty G, Lurie KG, Neumar RW, Metzger JM, Riess ML, Yannopoulos D. Bundled postconditioning therapies improve hemodynamics and neurologic recovery after 17 min of untreated cardiac arrest. Resuscitation. 2015 Feb;87:7-13.

Bedada FB, Chan SS, Metzger SK, Zhang L, Zhang J, Garry DJ, Kamp TJ, Kyba M, Metzger JM. Acquisition of a quantitative, stoichiometrically conserved ratiometric marker of maturation status in stem cell-derived cardiac myocytes. Stem Cell Reports. 2014 Oct 14;3(4):594-605.

Thompson BR, Metzger JM. Cell biology of sarcomeric protein engineering: disease modeling and therapeutic potential. Anat Rec (Hoboken). 2014 Sep;297(9):1663-9.

Wang W, Asp ML, Guerrero-Serna G, Metzger JM. Differential effects of S100 proteins A2 and A6 on cardiac Ca(2+) cycling and contractile performance. J Mol Cell Cardiol. 2014 Jul;72:117-25.

Thompson BR, Houang EM, Sham YY, Metzger JM. Molecular determinants of cardiac myocyte performance as conferred by isoform-specific TnI residues. Biophys J. 2014 May 20;106(10):2105-14.

Martindale JJ, Metzger JM. Uncoupling of increased cellular oxidative stress and myocardial ischemia reperfusion injury by directed sarcolemma stabilization. J Mol Cell Cardiol. 2014 Feb;67:26-37.

Heinis FI, Andersson KB, Christensen G, Metzger JM. Prominent heart organ-level performance deficits in a genetic model of targeted severe and progressive SERCA2 deficiency. PLoS One. 2013 Nov 4;8(11):e79609.

Asp ML, Martindale JJ, Metzger JM. Direct, differential effects of tamoxifen, 4-hydroxytamoxifen, and raloxifene on cardiac myocyte contractility and calcium handling. PLoS One. 2013 Oct 24;8(10):e78768.

Wang W, Barnabei MS, Asp ML, Heinis FI, Arden E, Davis J, Braunlin E, Li Q, Davis JP, Potter JD, Metzger JM. Noncanonical EF-hand motif strategically delays Ca2+ buffering to enhance cardiac performance. Nat Med. 2013 Mar;19(3):305-12.

Asp ML, Martindale JJ, Heinis FI, Wang W, Metzger JM. Calcium mishandling in diastolic dysfunction: mechanisms and potential therapies. Biochim Biophys Acta. 2013 Apr;1833(4):895-900.

Davis J, Yasuda S, Palpant NJ, Martindale J, Stevenson T, Converso K, Metzger JM. Diastolic dysfunction and thin filament dysregulation resulting from excitation-contraction uncoupling in a mouse model of restrictive cardiomyopathy. J Mol Cell Cardiol. 2012 Sep;53(3):446-57.

Palpant NJ, Houang EM, Sham YY, Metzger JM. pH-responsive titratable inotropic performance of histidine-modified cardiac troponin I. Biophys J. 2012 Apr 4;102(7):1570-9.

Barnabei MS, Metzger JM. Ex vivo stretch reveals altered mechanical properties of isolated dystrophin-deficient hearts. PLoS One. 2012;7(3):e32880.

Rasmussen TL, Kweon J, Diekmann MA, Belema-Bedada F, Song Q, Bowlin K, Shi X, Ferdous A, Li T, Kyba M, Metzger JM, Koyano-Nakagawa N, Garry DJ. ER71 directs mesodermal fate decisions during embryogenesis. Development. 2011 Nov;138(21):4801-12.

Townsend D, Daly M, Chamberlain JS, Metzger JM. Age-dependent dystrophin loss and genetic reconstitution establish a molecular link between dystrophin and heart performance during aging. Mol Ther. 2011 Oct;19(10):1821-5. doi: 10.1038/mt.2011.120. Epub 2011 Jul 5.

Townsend D, Yasuda S, McNally E, Metzger JM. Distinct pathophysiological mechanisms of cardiomyopathy in hearts lacking dystrophin or the sarcoglycan complex. FASEB J. 2011 Sep;25(9):3106-14. Epub 2011 Jun 10.

Vandenboom R, Herron T, Favre E, Albayya FP, Metzger JM. Gene transfer, expression, and sarcomeric incorporation of a headless myosin molecule in cardiac myocytes: evidence for a reserve in myofilament motor function. Am J Physiol Heart Circ Physiol. 2011 Feb;300(2):H574-82. Epub 2010 Nov 26.

Palpant NJ, Bedada FB, Peacock B, Blazar BR, Metzger JM, Tolar J. Cardiac disease in mucopolysaccharidosis type I attributed to catecholaminergic and hemodynamic deficiencies. Am J Physiol Heart Circ Physiol. 2011 Jan;300(1):H356-65. Epub 2010 Nov 12.

Barnabei MS, Palpant NJ, Metzger JM. Influence of genetic background on ex vivo and in vivo cardiac function in several commonly used inbred mouse strains. Physiol Genomics. 2010 Oct;42A(2):103-13. Epub 2010 Jul 13.

Palpant NJ, Houang EM, Delport W, Hastings KE, Onufriev AV, Sham YY, Metzger JM. Pathogenic peptide deviations support a model of adaptive evolution of chordate cardiac performance by troponin mutations.Physiol Genomics. 2010 Jul 7;42(2):287-99. Epub 2010 Apr 27.

Townsend D, Turner I, Yasuda S, Martindale J, Davis J, Shillingford M, Kornegay JN, Metzger JM. Chronic administration of membrane sealant prevents severe cardiac injury and ventricular dilatation in dystrophic dogs. J Clin Invest. 2010 Apr 1;120(4):1140-50. doi: 10.1172/JCI41329. Epub 2010 Mar 15.

Davis J, Metzger JM. Combinatorial effects of double cardiomyopathy mutant alleles in rodent myocytes: a predictive cellular model of myofilament dysregulation in disease. PLoS One. 2010 Feb 10;5(2):e9140.

Parvalbumin: Targeting calcium handling in cardiac diastolic dysfunction. Wang W, Martindale J, Metzger JM. Gen Physiol Biophys. 2009;28 Spec No Focus:F3-6.

Yasuda S, Townsend D, Michele DE, Favre EG, Day SM, and Metzger JM . Dystrophic Heart Failure Blocked by Membrane Sealant Poloxamer. Nature , 18:1025-9. 2005.

Day SM, Westfall MV, Fomicheva EV, La Cross N, Yasuda S, Hoyer K, Ingwall JS, Metzger JM . Histidine Button Engineered into Cardiac Troponin I Protects the Heart from Ischemic Contractile Failure. Nature Medicine, Feb; 12(2):181-9 2006.

Chamberlain JS, Metzger JM , Reyes M, Townsend D and Faulkner J. Dystrophin-deficient mdx mice display a reduced life span and are susceptible to spontaneous rhabdomyosarcoma. The FASEB Journal . July; 21:1-10, 2007.

Townsend D, Yasuda S, Li S, Chamberlain JS, Metzger JM . Emergent dilated cardiomyopathy caused by targeted repair of dystrophic skeletal muscle. Molecular Therapy. 16(5):832-5, 2008.

Davis J, Westfall MV, Townsend D, Blankinship M, Herron TJ, Guerrero-Serna G, Wang W, Devaney E, Metzger JM. Designing heart performance by gene transfer. Physiological Reviews Oct;88(4):1567-651, 2008.

Fomicheva EV, Turner II, Edwards YG, Hoff J, Arden E, D'Alecy LG, Metzger JM . Double oxygen- sensing vector system for robust hypoxia/ischemia-regulated gene induction in cardiac muscle in vitro and in vivo. Molecular Therapy. 16(9):1594-601, 2008.

Joseph Metzger