Curriculum vitae
Professional Experience
Since Oct 2017 Westfälische Wilhelms-Universität Münster, Inst. of Physiology II, Professor Head of Inst. Since 2016 Certified physiology teacher ("Fachphysiologe") of the German Physiological Society Since Apr 2010 Adjunct Professor of Cardiac Mechanotransduction, Heart Center, University Medicine Göttingen, Germany Apr 2009 - Oct 2017 Ruhr University Bochum, Inst. of Physiology, Professor Head of Dept. of Cardiovascular Physiology Oct 2003 – Mar 2009 University of Muenster, Inst. of General Zoology and Genetics, Professor Head, Physiology and Biophysics Unit - Cell Biology, Physiology and Biophysics of Cardiac and Skeletal Muscle- Lectures, Seminars, Practical Classes in Biology and Human Physiology Oct 1999 – Sept 2003 University of Heidelberg, Inst. of Physiology and Pathophysiology, Assistant Professor of Physiology Heisenberg Fellow of the German Research Foundation Director of the Cellular Muscle Mechanics Lab - Subject of Study: Cell Biology and Biophysics of Muscle Proteins - Lectures, Seminars in Human Physiology Apr 2001 – Oct 2001 Mayo Clinic Rochester, Dept. of Physiology and Biophysics, Visiting Professor - Research Group of Prof. J. M. Fernandez - Atomic Force Microscopy of Engineered Elastic Proteins Oct 1994 – Sept 1999 University of Heidelberg, Germany, Institute of Physiology II, Assistant Professor of Physiology - Group Leader, Mechanics of Elastic Filaments in Muscle - Seminars, Practical Classes in Human Physiology Oct 1991 – Sep 1994 University of Washington, Seattle, Center for Bioengineering, Postdoctoral Fellow - Research Group of Prof. G. H. Pollack - Cardiac Myofibrillar Mechanics Degrees
1998 University of Heidelberg, Germany, D.Sc. ("Habilitation"), Physiology 1991 Martin-Luther University Halle-Wittenberg, Germany, Ph.D., Animal Physiology 1988 Martin-Luther University Halle-Wittenberg, Germany, Ph. D. student (Institute of Physiology, Institute of Zoology) Awards and Honors
Since 2016 Elected Member (Academician) of the Göttingen Academy of Sciences, Germany Since 2016 Elected Fellow of the International Society for Heart Research (FISHR) Since 2015 Principal Investigator, German Center for Cardiovascular Research (DZHK), Göttingen site 2013 Franz Maximilian Groedel Research Price of the German Society of Cardiology Since 2013 Fellow of the American Heart Association-BCVS council (FAHA) 2011-2015 Joint Research Grant from the European Union, FP7 program, MEDIA ("Metabolic Road to Diastolic Heart Failure") Since 2010 Invited Fellow of the European Society of Cardiology (FESC) 1999 - 2003 Heisenberg Fellowship (career development award) of the German Research Foundation Since 1996 Continuous research funding by the German Research Foundation; (multiple research grants) Publications
2017- Membrane Remodeling by a Bacterial Phospholipid-Methylating Enzyme.
Danne L, Aktas M, Unger A, Linke WA, Erdmann R, Narberhaus F , MBio. (2017) , 8(1) - Defined Engineered Human Myocardium with Advanced Maturation for Applications in Heart Failure Modelling and Repair
Tiburcy M, Hudson JE, Balfanz P, Schlick SF, Meyer T, Chang Liao ML, Levent E, Raad F, Zeidler S, Wingender E, Riegler J, Wang M, Gold JD, Kehat I, Wettwer E, Ravens U, Dierickx P, van Laake L, Goumans MJ, Khadjeh S, Toischer K, Hasenfuss G, Couture LA, Unger A, Linke WA, Araki T, Neel B, Keller G, Gepstein L, Wu JC, Zimmermann WH , Circulation. (2017) : [Epub ahead of print] - Titin-truncating variants affect heart function in disease cohorts and the general population.
Schafer S, de Marvao A, Adami E, Fiedler LR, Ng B, Khin E, Rackham OJ, van Heesch S, Pua CJ, Kui M, Walsh R, Tayal U, Prasad SK, Dawes TJ, Ko NS, Sim D, Chan LL, Chin CW, Mazzarotto F, Barton PJ, Kreuchwig F, de Kleijn DP, Totman T, Biffi C, Tee N, Rueckert D, Schneider V, Faber A, Regitz-Zagrosek V, Seidman JG, Seidman CE, Linke WA, Kovalik JP, O'Regan D, Ware JS, Hubner N, Cook SA , Nat Genet. (2017) , 49(1) : 46-53
- Cardioprotection and lifespan extension by the natural polyamine spermidine.
Eisenberg T, Abdellatif M, Schroeder S, Primessnig U, Stekovic S, Pendl T, Harger A, Schipke J, Zimmermann A, Schmidt A, Tong M, Ruckenstuhl C, Dammbrueck C, Gross AS, Herbst V, Magnes C, Trausinger G, Narath S, Meinitzer A, Hu Z, Kirsch A, Eller K, Carmona-Gutierrez D, Büttner S, Pietrocola F, Knittelfelder O, Schrepfer E, Rockenfeller P, Simonini C, Rahn A, Horsch M, Moreth K, Beckers J, Fuchs H, Gailus-Durner V, Neff F, Janik D, Rathkolb B, Rozman J, de Angelis MH, Moustafa T, Haemmerle G, Mayr M, Willeit P, von Frieling-Salewsky M, Pieske B, Scorrano L, Pieber T, Pechlaner R, Willeit J, Sigrist SJ, Linke WA, Mühlfeld C, Sadoshima J, Dengjel J, Kiechl S, Kroemer G, Sedej S, Madeo F. , Nat Med. (2016) , 22(12) : 1428-1438 - Expanding the phenotype of BICD2 mutations toward skeletal muscle involvement.
Unger A, Dekomien G, Güttsches A, Dreps T, Kley R, Tegenthoff M, Ferbert A, Weis J, Heyer C, Linke WA, Martinez-Carrera L, Storbeck M, Wirth B, Hoffjan S, Vorgerd M. , Neurology. (2016) , 87(21) : 2235-2243 - Left Atrial Remodeling and Atrioventricular Coupling in a Canine Model of Early Heart Failure With Preserved Ejection Fraction.
Zakeri R, Moulay G, Chai Q, Ogut O, Hussain S, Takahama H, Lu T, Wang XL, Linke WA, Lee HC, Redfield MM. , Circ Heart Fail. (2016) , 9(10) - Sphingosine-1-Phosphate Receptor 1 Regulates Cardiac Function by Modulating Ca2+ Sensitivity and Na+/H+ Exchange and Mediates Protection by Ischemic Preconditioning.
Keul P, van Borren MM, Ghanem A, Müller FU, Baartscheer A, Verkerk AO, Stümpel F, Schulte JS, Hamdani N, Linke WA, van Loenen P, Matus M, Schmitz W, Stypmann J, Tiemann K, Ravesloot JH, Alewijnse AE, Hermann S, Spijkers LJ, Hiller KH, Herr D, Heusch G, Schäfers M, Peters SL, Chun J, Levkau B. , J Am Heart Assoc. (2016) , 5(5) - Titin stiffness modifies the force-generating region of muscle sarcomeres.
Li Y, Lang P, Linke WA. , Sci Rep. (2016) , 6 : 24492 - Work Done by Titin Protein Folding Assists Muscle Contraction.
Rivas-Pardo JA, Eckels EC, Popa I, Kosuri P, Linke WA, Fernández JM. , Cell Rep. (2016) , 14(6) : 1339-1347 - Functional characterization of the novel DES mutation p.L136P associated with dilated cardiomyopathy reveals a dominant filament assembly defect.
Brodehl A, Dieding M, Biere N, Unger A, Klauke B, Walhorn V, Gummert J, Schulz U, Linke WA, Gerull B, Vorgert M, Anselmetti D, Milting H , J Mol Cell Cardiol. (2015) , 91 : 207-214 - Cardiac contractility modulation signals improve exercise intolerance and maladaptive regulation of cardiac key proteins for systolic and diastolic function in HFpEF.
Tschöpe C, Van Linthout S, Spillmann F, Klein O, Biewener S, Remppis A, Gutterman D, Linke WA, Pieske B, Hamdani N, Roser M. , Int J Cardiol. (2016) , 203 : 1061-1066 - Molecular and structural transition mechanisms in long-term volume overload.
Mohamed BA, Schnelle M, Khadjeh S, Lbik D, Herwig M, Linke WA, Hasenfuss G, Toischer K. , Eur J Heart Fail. (2016) , 18(4) : 362-71
- Myocardial Microvascular Inflammatory Endothelial Activation in Heart Failure With Preserved Ejection Fraction.
Franssen C, Chen S, Unger A, Korkmaz HI, De Keulenaer GW, Tschöpe C, Leite-Moreira AF, Musters R, Niessen HW, Linke WA, Paulus WJ, Hamdani N. , JACC Heart Fail. (2015) , 4(4) : 312-24 - Myofibrillar instability exacerbated by acute exercise in filaminopathy.
Chevessier F, Schuld J, Orfanos Z, Plank AC, Wolf L, Maerkens A, Unger A, Schlötzer-Schrehardt U, Kley RA, von Hörsten S, Marcus K, Linke WA, Vorgerd M, van der Ven PF, Fürst DO, Schröder R. , Hum Mol Genet. (2015) , 24(25) : 7207-20 - A porcine model of hypertensive cardiomyopathy: implications for heart failure with preserved ejection fraction.
Schwarzl M, Hamdani N, Seiler S, Alogna A, Manninger M, Reilly S, Zirngast B, Kirsch AH, Steendijk P, Verderber J, Zweiker D, Eller P, Hoefler G, Schauer S, Eller K, Maechler H, Pieske B, Linke WA, Casadei B, Post H. , Am J Physiol Heart Circ Physiol. (2015) , 309(9) : H1407-18 - HEART DISEASE. Titin mutations in iPS cells define sarcomere insufficiency as a cause of dilated cardiomyopathy.
Hinson JT, Chopra A, Nafissi N, Polacheck WJ, Benson CC, Swist S, Gorham J, Yang L, Schafer S, Sheng CC, Haghighi A, Homsy J, Hubner N, Church G, Cook SA, Linke WA, Chen CS, Seidman JG, Seidman CE. , Science (2015) , 349 : 982-986 - Syndecan-4 is a key determinant of collagen cross-linking and passive myocardial stiffness in the pressure-overloaded heart.
Herum KM, Lunde IG, Skrbic B, Louch WE, Hasic A, Boye S, Unger A, Brorson SH, Sjaastad I, Tønnessen T, Linke WA, Gomez MF, Christensen G. , Cardiovasc Res. (2015) , 106(2) : 217-26 - Emerging importance of oxidative stress in regulating striated muscle elasticity.
Beckendorf L, Linke WA. , J Muscle Res Cell Motil. (2015) , 36(1) : 25-36
- FHL2 expression and variants in hypertrophic cardiomyopathy.
Friedrich FW, Reischmann S, Schwalm A, Unger A, Ramanujam D, Münch J, Müller OJ, Hengstenberg C, Galve E, Charron P, Linke WA, Engelhardt S, Patten M, Richard P, van der Velden J, Eschenhagen T, Isnard R, Carrier L. , Basic Res Cardiol. (2014) , 109(6) : 451 - Interleukin-6 receptor inhibition modulates the immune reaction and restores titin phosphorylation in experimental myocarditis.
Savvatis K, Müller I, Fröhlich M, Pappritz K, Zietsch C, Hamdani N, Grote K, Schieffer B, Klingel K, Van Linthout S, Linke WA, Schultheiss HP, Tschöpe C. , Basic Res Cardiol. (2014) , 109(6) : 449 - Left ventricular diastolic dysfunction and myocardial stiffness in diabetic mice is attenuated by inhibition of dipeptidyl peptidase 4.
Hamdani N, Hervent AS, Vandekerckhove L, Matheeussen V, Demolder M, Baerts L, De Meester I, Linke WA, Paulus WJ, De Keulenaer GW , Cardiovasc Res. (2014) , 104(3) : 423-31 - Heart failure with preserved ejection fraction.
Gladden JD, Linke WA, Redfield MM. , Pflugers Arch. (2014) , 466(6) : 1037-53 - S-glutathionylation of cryptic cysteines enhances titin elasticity by blocking protein folding.
Alegre-Cebollada J, Kosuri P, Giganti D, Eckels E, Rivas-Pardo JA, Hamdani N, Warren CM, Solaro RJ, Linke WA, Fernández JM. , Cell. (2014) , 156(6) : 1235-46 - Gigantic business: titin properties and function through thick and thin.
Linke WA, Hamdani N. , Circ Res. (2014) , 114(6) : 1052-68 - Meeting highlights from the 2013 European Society of Cardiology Heart Failure Association Winter Meeting on Translational Heart Failure Research.
Hohl M, Ardehali H, Azuaje FJ, Breckenridge RA, Doehner W, Eaton P, Ehret GB, Fujita T, Gaetani R, Giacca M, Hasenfuß G, Heymans S, Leite-Moreira AF, Linke WA, Linz D, Lyon A, Mamas MA, Orešič M, Papp Z, Pedrazzini T, Piepoli M, Prosser B, Rizzuto R, Tarone G, Tian R, van Craenenbroeck E, van Rooij E, Wai T, Weiss G, Maack C. , Eur J Heart Fail. (2014) , 16(1) : 6-14 - Human myocytes are protected from titin aggregation-induced stiffening by small heat shock proteins.
Kötter S, Unger A, Hamdani N, Lang P, Vorgerd M, Nagel-Steger L, Linke WA. , J Cell Biol. (2014) , 204(2) : 187-202
- Myocardial Titin Hypophosphorylation Importantly Contributes to Heart Failure with Preserved Ejection Fraction in a Rat Metabolic Risk Model.
Hamdani N, Franssen C, Lourenço A, Falcão-Pires I, Fontoura D, Leite S, Plettig L, López B, Ottenheijm CA, Becher MP, González A, Tschöpe C, Díez J, Linke WA, Leite-Moreira AF, Paulus WJ. , Circ Heart Fail. (2013) : [Epub ahead of print] - Mena/VASP and alphaII-Spectrin complexes regulate cytoplasmic actin networks in cardiomyocytes and protect from conduction abnormalities and dilated cardiomyopathy.
Benz PM, Merkel CJ, Offner K, Abeßer M, Ullrich M, Fischer T, Bayer B, Wagner H, Gambaryan S, Ursitti JA, Adham IM, Linke WA, Feller SM, Fleming I, Renné T, Frantz S, Unger A, Schuh K. , Cell Commun Signal. (2013) , 11(1) : 56 - Untangling regulatory networks to spot drivers and modulators of cardiac disease.
Swist S, Linke WA. , J Mol Cell Cardiol. (2013) , 63C : 1-3 - Differential changes in titin domain phosphorylation increase myofilament stiffness in failing human hearts.
Kötter S, Gout L, Von Frieling-Salewsky M, Müller AE, Helling S, Marcus K, Dos Remedios C, Linke WA, Krüger M. , Cardiovasc Res. (2013) , 99(4) : 648-56 - 7th Ascona International Workshop on Cardiomyocyte Biology: Cardiac pathways of differentiation, metabolism and contraction.
Linke WA, Schaub MC. , Biochim Biophys Acta. (2013) , 1833(4) : 781-2 - Crucial Role for Ca2+/Calmodulin-Dependent Protein Kinase-II in Regulating Diastolic Stress of Normal and Failing Hearts via Titin Phosphorylation.
Hamdani N, Krysiak J, Kreusser MM, Neef S, Dos Remedios CG, Maier LS, Krüger M, Backs J, Linke WA. , Circ Res. (2013) , 112(4) : 664-74 - Deranged Myofilament Phosphorylation and Function in Experimental Heart Failure with Preserved Ejection Fraction.
Hamdani N, Bishu KG, von Frieling-Salewsky M, Redfield MM, Linke WA. , Cardiovasc Res. (2013) , 97(3) : 464-71 - Lysine methyltransferase Smyd2 regulates Hsp90-mediated protection of the sarcomeric titin springs and cardiac function.
Voelkel T, Andresen C, Unger A, Just S, Rottbauer W, Linke WA , Biochim Biophys Acta. (2013) , 1833(4) : 812-22
- King of hearts: a splicing factor rules cardiac proteins.
Linke WA, Bücker S. , Nat Med. (2012) , 18(5) : 660-1 - Evidence for FHL1 as a novel disease gene for isolated hypertrophic cardiomyopathy.
Friedrich FW, Wilding BR, Reischmann S, Crocini C, Lang P, Charron P, Müller OJ, McGrath MJ, Vollert I, Hansen A, Linke WA, Hengstenberg C, Bonne G, Morner S, Wichter T, Madeira H, Arbustini E, Eschenhagen T, Mitchell CA, Isnard R, Carrier L. , Hum Mol Genet. (2012) , 21(14) : 3237-54 - Age-dependent changes in contractile function and passive elastic properties of myocardium from mice lacking muscle LIM protein (MLP).
Unsöld B, Schotola H, Jacobshagen C, Seidler T, Sossalla S, Emons J, Klede S, Knöll R, Guan K, El-Armouche A, Linke WA, Kögler H, Hasenfuss G. , Eur J Heart Fail. (2012) , 14(4) : 430-7 - Alteration of the beta-adrenergic signaling pathway in human heart failure.
Hamdani N, Linke WA. , Curr Pharm Biotechnol. (2012) : Jan 20. [Epub ahead of print] - Smyd2 controls cytoplasmic lysine methylation of Hsp90 and myofilament organization.
Donlin LT, Andresen C, Just S, Rudensky E, Pappas CT, Kruger M, Jacobs EY, Unger A, Zieseniss A, Dobenecker MW, Voelkel T, Chait BT, Gregorio CC, Rottbauer W, Tarakhovsky A, Linke WA. , Genes Dev. (2012) , 26(2) : 114-9
- Sildenafil and B-type natriuretic Peptide acutely phosphorylate titin and improve diastolic distensibility in vivo.
Bishu K, Hamdani N, Mohammed SF, Kruger M, Ohtani T, Ogut O, Brozovich FV, Burnett JC Jr, Linke WA, Redfield MM. , Circulation (2011) , 124(25) : 2882-91 - Transmural heterogeneity of myofilament function and sarcomeric protein phosphorylation in remodeled myocardium of pigs with a recent myocardial infarction.
van der Velden J, Merkus D, de Beer V, Hamdani N, Linke WA, Boontje NM, Stienen GJ, Duncker DJ. , Front Physiol. (2011) , 2 : Article 83 - Terminal differentiation, advanced organotypic maturation, and modeling of hypertrophic growth in engineered heart tissue.
Tiburcy M, Didié M, Boy O, Christalla P, Döker S, Naito H, Karikkineth BC, El-Armouche A, Grimm M, Nose M, Eschenhagen T, Zieseniss A, Katschinksi DM, Hamdani N, Linke WA, Yin X, Mayr M, Zimmermann WH. , Circ Res. (2011) , 109(10) : 1105-14 - Telethonin Deficiency Is Associated With Maladaptation to Biomechanical Stress in the Mammalian Heart.
Knöll R, Linke WA, Zou P, Miocic S, Kostin S, Buyandelger B, Ku CH, Neef S, Bug M, Schäfer K, Knöll G, Felkin LE, Wessels J, Toischer K, Hagn F, Kessler H, Didié M, Quentin T, Maier LS, Teucher N, Unsöld B, Schmidt A, Birks EJ, Gunkel S, Lang P, Granzier H, Zimmermann WH, Field LJ, Faulkner G, Dobbelstein M, Barton PJ, Sattler M, Wilmanns M, Chien KR , Circ Res. (2011) , 109(7) : 758-69 - Conformation-regulated mechanosensory control via titin domains in cardiac muscle.
Voelkel T, Linke WA. , Pflugers Arch. (2011) , 462(1) : 143-54 - The giant protein titin: a regulatory node that integrates myocyte signaling pathways.
Krüger M, Linke WA , J Biol Chem. (2011) , 286(12) : 9905-12 (Review)
- Modulation of Human Ether A Gogo Related Channels by CASQ2 Contributes to Etiology of Catecholaminergic Polymorphic Ventricular Tachycardia (CPVT)
Eckey K, Strutz-Seebohm N, Katz G, Fuhrmann G, Henrion U, Pott L, Linke WA, Arad M, Lang F, Seebohm G , Cell Physiol Biochem (2010) , 26(4-5) : 503-12 - Molecular Giant Vulnerable to Oxidative Damage. Titin Joins the Club of Proteins Degraded by Matrix Metalloproteinase-2
Linke WA , Circulation (2010) , 122(20) : 2002-4 - Biomaterials: spider strength and stretchability
Linke WA , Nat Chem Biol (2010) , 6(10) : 702-3 - Treatment of heart failure with normal ejection fraction.
Hamdani N, Paulus WJ. , Curr Treat Options Cardiovasc Med. (2011) , 13(1) : 26-34 - Differential cardiac remodeling in preload versus afterload
Toischer K, Rokita AG, Unsöld B, Zhu W, Kararigas G, Sossalla S, Reuter SP, Becker A, Teucher N, Seidler T, Grebe C, Preuss L, Gupta SN, Schmidt K, Lehnart SE, Krüger M, Linke WA, Backs J, Regitz-Zagrosek V, Schäfer K, Field LJ, Maier LS, Hasenfuss G , Circulation (2010) , 122(10) : 993-1003 - Multiple potential molecular contributors to atrial hypocontractility caused by atrial tachycardia remodeling in dogs
Wakili R, Yeh YH, Yan Qi X, Greiser M, Chartier D, Nishida K, Maguy A, Villeneuve LR, Boknik P, Voigt N, Krysiak J, Kääb S, Ravens U, Linke WA, Stienen GJ, Shi Y, Tardif JC, Schotten U, Dobrev D, Nattel S , Circ Arrhythm Electrophysiol (2010) , 3(5) : 530-41 - The giant protein titin as an integrator of myocyte signaling pathways
Linke WA, Krüger M , Physiology (Bethesda) (2010) , 25(3) : 186-98 (Review) - Insulin signaling regulates cardiac titin properties in heart development and diabetic cardiomyopathy
Krüger M, Babicz K, von Frieling-Salewsky M, Linke WA , J Mol Cell Cardiol (2010) , 48(5) : 910-16 - Regulation of oscillatory contraction in insect flight muscle by troponin
Krzic U, Rybin V, Leonard KR, Linke WA, Bullard B , J Mol Biol (2010) , 397(1) : 110-18 - A common MLP (muscle LIM protein) variant is associated with cardiomyopathy
Knöll R, Kostin S, Klede S, Savvatis K, Klinge L, Stehle I, Gunkel S, Kötter S, Babicz K, Sohns M, Miocic S, Didié M, Knöll G, Zimmermann WH, Thelen P, Bickeböller H, Maier LS, Schaper W, Schaper J, Kraft T, Tschöpe C, Linke WA, Chien KR , Circ Res (2010) , 106(4) : 695-704
- Prevention of myofilament dysfunction by beta-blocker therapy in postinfarct remodeling
Duncker DJ, Boontje NM, Merkus D, Versteilen A, Krysiak J, Mearini G, El-Armouche A, de Beer VJ, Lamers JM, Carrier L, Walker LA, Linke WA, Stienen GJ, van der Velden J , Circ Heart Fail (2009) , 2(3) : 233-42 - Modulation of titin-based stiffness by disulfide bonding in the cardiac titin N2-B unique sequence
Grützner A, Garcia-Manyes S, Kötter S, Badilla CL, Fernandez JM, Linke WA , Biophys J (2009) , 97(3) : 825-34 - Titin-based mechanical signalling in normal and failing myocardium
Krüger M, Linke WA , J Mol Cell Cardiol (2009) , 46(4) : 490-8 (Review) - Titin and titin-associated proteins in myocardial stress-sensing and mechanical dysfunction
Linke WA , Mechanosensitivity in cells and tissues, Mechanosensitivity of the heart (A. Kamkin & Kiseleva, I., Eds.) Springer, Heidelberg 4 (2009) : (Review) - Functional role of the extended loop 2 in the myosin 9b head for binding F-actin
Struchholz S, Elfrink K, Pieper U, Kalhammer G, Honnert U, Grützner A, Linke WA, Liao W, Bähler M , J Biol Chem (2009) , 284(6) : 3663-71 - Protein kinase G modulates human myocardial passive stiffness by phosphorylation of the titin springs
Krüger M, Kötter S, Grützner A, Lang P, Andresen C, Redfield MM, Butt E, dos Remedios CG, Linke WA , Circ Res (2009) , 104(1) : 87-94
- Titin isoforms, extracellular matrix, and global chamber remodeling in experimental dilated cardiomyopathy: functional implications and mechanistic insight
Jaber WA, Maniu C, Krysiak J, Shapiro BP, Meyer DM, Linke WA, Redfield MM , Circ Heart Fail (2008) , 1(3) : 192-9 - Thyroid hormone regulates developmental titin isoform transitions via the phosphatidylinositol-3-kinase/ AKT pathway
Krüger M, Sachse C, Zimmermann WH, Eschenhagen T, Klede S, Linke WA , Circ Res (2008) , 102(4) : 439-47 - Mineralocorticoid signaling in transition to heart failure with normal ejection fraction
Shapiro BP, Owan TE, Mohammed S, Kruger M, Linke WA, Burnett JC Jr, Redfield MM , Hypertension (2008) , 51(2) : 289-95 - Pulling single molecules of titin by AFM--recent advances and physiological implications
Linke WA, Grützner A , Pflugers Arch (2008) , 456(1) : 101-15 (Review) - Sense and stretchability: the role of titin and titin-associated proteins in myocardial stress-sensing and mechanical dysfunction
Linke WA , Cardiovasc Res (2008) , 77(4) : 637-48 (Review) - Taschenatlas Physiologie (Lehrbuch)
Fahlke/Linke/Rassler/Wiesner (Eds) , Elsevier (2008) , 1. Auflage
- Acute and chronic ventricular-arterial coupling in systole and diastole: insights from an elderly hypertensive model
Shapiro BP, Lam CS, Patel JB, Mohammed SF, Kruger M, Meyer DM, Linke WA, Redfield MM , Hypertension (2007) , 50(3) : 503-11
- Fibre type-specific increase in passive muscle tension in spinal cord-injured subjects with spasticity
Olsson MC, Krüger M, Meyer LH, Ahnlund L, Gransberg L, Linke WA, Larsson L , J Physiol (2006) , 577(Pt 1) : 339-52 - Protein kinase-A phosphorylates titin in human heart muscle and reduces myofibrillar passive tension
Krüger M, Linke WA , J Muscle Res Cell Motil (2006) , 27(5-7) : 435-44 - Mechanical properties of cardiac titin's N2B-region by single-molecule atomic force spectroscopy
Leake MC, Grützner A, Krüger M, Linke WA , J Struct Biol (2006) , 155(2) : 263-72 - Developmental changes in passive stiffness and myofilament Ca2+ sensitivity due to titin and troponin-I isoform switching are not critically triggered by birth
Krüger M, Kohl T, Linke WA , Am J Physiol Heart Circ Physiol (2006) , 291(2) : H496-506 (Erratum in: Am J Physiol Heart Circ Physiol (2007) 292(1):H726) - Myocardial structure and function differ in systolic and diastolic heart failure
van Heerebeek L, Borbély A, Niessen HW, Bronzwaer JG, van der Velden J, Stienen GJ, Linke WA, Laarman GJ, Paulus WJ , Circulation (2006) , 113(16) : 1966-73 - The molecular elasticity of the insect flight muscle proteins projectin and kettin
Bullard B, Garcia T, Benes V, Leake MC, Linke WA, Oberhauser AF , Proc Natl Acad Sci U S A (2006) , 103(12) : 4451-6
- Plasticity of cardiac titin/connectin in heart development
Opitz CA, Linke WA , J Muscle Res Cell Motil (2005) , 26(6-8) : 333-42 - Isoform diversity of giant proteins in relation to passive and active contractile properties of rabbit skeletal muscles
Prado LG, Makarenko I, Andresen C, Krüger M, Opitz CA, Linke WA , J Gen Physiol (2005) , 126(5) : 461-80
- Multiple sources of passive stress relaxation in muscle fibres
Linke WA, Leake MC , Phys Med Biol (2004) , 49(16) : 3613-27 - Passive stiffness changes caused by upregulation of compliant titin isoforms in human dilated cardiomyopathy hearts
Makarenko I, Opitz CA, Leake MC, Neagoe C, Kulke M, Gwathmey JK, del Monte F, Hajjar RJ, Linke WA , Circ Res (2004) , 95(7) : 708-16 - Developmentally regulated switching of titin size alters myofibrillar stiffness in the perinatal heart
Opitz CA, Leake MC, Makarenko I, Benes V, Linke WA , Circ Res (2004) , 94(7) : 967-75 - A troponin switch that regulates muscle contraction by stretch instead of calcium
Agianian B, Krzic U, Qiu F, Linke WA, Leonard K, Bullard B , EMBO J (2004) , 23(4) : 772-9 - Association of the chaperone alphaB-crystallin with titin in heart muscle
Bullard B, Ferguson C, Minajeva A, Leake MC, Gautel M, Labeit D, Ding L, Labeit S, Horwitz J, Leonard KR, Linke WA , J Biol Chem (2004) , 279(9) : 7917-24
- Gigantic variety: expression patterns of titin isoforms in striated muscles and consequences for myofibrillar passive stiffness
Neagoe C, Opitz CA, Makarenko I, Linke WA , J Muscle Res Cell Motil (2003) , 24(2-3) : 175-89 - Damped elastic recoil of the titin spring in myofibrils of human myocardium
Opitz CA, Kulke M, Leake MC, Neagoe C, Hinssen H, Hajjar RJ, Linke WA , Proc Natl Acad Sci U S A (2003) , 100(22) : 12688-93 - Alcohol affects the skeletal muscle proteins, titin and nebulin in male and female rats
Hunter RJ, Neagoe C, Järveläinen HA, Martin CR, Lindros KO, Linke WA, Preedy VR , J Nutr (2003) , 133(4) : 1154-7 - Titin stiffness in heart disease
Linke WA , Circulation (2003) , 107(11) : e73 - Cardiac titin: Molecular basis of elasticity and cellular contribution to elastic and viscous stiffness components in myocardium
Linke WA, Fernandez JM , In Mechanics of Elastic Biomolecules (Linke, W.A., H. Granzier & M. Kellermayer, Hrg.) Kluwer: Dordrecht (2003) : 483-497 - Varieties of elastic protein in invertebrate muscles
Bullard B, Linke WA, Leonard K , In Mechanics of Elastic Biomolecules (Linke, W.A., H. Granzier & M. Kellermayer, Hrg.) Kluwer: Dordrecht (2003) : 435-447
- Cardiac titin: molecular basis of elasticity and cellular contribution to elastic and viscous stiffness components in myocardium
Linke WA, Fernandez JM , J Muscle Res Cell Motil (2002) , 23(5-6) : 483-97 - Varieties of elastic protein in invertebrate muscles
Bullard B, Linke WA, Leonard K , J Muscle Res Cell Motil (2002) , 23(5-6) : 435-47 (Review) - Passive stiffness changes in soleus muscles from desmin knockout mice are not due to titin modifications
Anderson J, Joumaa V, Stevens L, Neagoe C, Li Z, Mounier Y, Linke WA, Goubel F , Pflugers Arch (2002) , 444(6) : 771-6 - Titin isoform switch in ischemic human heart disease
Neagoe C, Kulke M, del Monte F, Gwathmey JK, de Tombe PP, Hajjar RJ, Linke WA , Circulation (2002) , 106(11) : 1333-41 - Reverse engineering of the giant muscle protein titin
Li H, Linke WA, Oberhauser AF, Carrion-Vazquez M, Kerkvliet JG, Lu H, Marszalek PE, Fernandez JM , Nature (2002) , 418(6901) : 998-1002 - PEVK domain of titin: an entropic spring with actin-binding properties
Linke WA, Kulke M, Li H, Fujita-Becker S, Neagoe C, Manstein DJ, Gautel M, Fernandez JM , J Struct Biol (2002) , 137(1-2) : 194-205 - Titin-based contribution to shortening velocity of rabbit skeletal myofibrils
Minajeva A, Neagoe C, Kulke M, Linke WA , J Physiol (2002) , 540(Pt 1) : 177-88
- Interaction between PEVK-titin and actin filaments: origin of a viscous force component in cardiac myofibrils
Kulke M, Fujita-Becker S, Rostkova E, Neagoe C, Labeit D, Manstein DJ, Gautel M, Linke WA , Circ Res (2001) , 89(10) : 874-81 - Differentiation- and stress-dependent nuclear cytoplasmic redistribution of myopodin, a novel actin-bundling protein
Weins A, Schwarz K, Faul C, Barisoni L, Linke WA, Mundel P , J Cell Biol (2001) , 155(3) : 393-404 - Kettin, a major source of myofibrillar stiffness in Drosophila indirect flight muscle
Kulke M, Neagoe C, Kolmerer B, Minajeva A, Hinssen H, Bullard B, Linke WA , J Cell Biol (2001) , 154(5) : 1045-57 - Unfolding of titin domains explains the viscoelastic behavior of skeletal myofibrils
Minajeva A, Kulke M, Fernandez JM, Linke WA , Biophys J (2001) , 80(3) : 1442-51 - Hypercontractile properties of cardiac muscle fibers in a knock-in mouse model of cardiac myosin-binding protein-C
Witt CC, Gerull B, Davies MJ, Centner T, Linke WA, Thierfelder L , J Biol Chem (2001) , 276(7) : 5353-9
- Titin elasticity in the context of the sarcomere: force and extensibility measurements on single myofibrils
Linke WA , Adv Exp Med Biol (2000) , 481 : 179-206 (Review) - Stretching molecular springs: elasticity of titin filaments in vertebrate striated muscle
Linke WA , Histol Histopathol (2000) , 15(3) : 799-811 (Review) - Sarcomere length-tension relationship of rat cardiac myocytes at lengths greater than optimum
Weiwad WK, Linke WA, Wussling MH , J Mol Cell Cardiol (2000) , 32(2) : 247-59
- I-band titin in cardiac muscle is a three-element molecular spring and is critical for maintaining thin filament structure
Linke WA, Rudy DE, Centner T, Gautel M, Witt C, Labeit S, Gregorio CC , J Cell Biol (1999) , 146(3) : 631-44 - The titin cDNA sequence and partial genomic sequences: insights into the molecular genetics, cell biology and physiology of the titin filament system
Kolmerer B, Witt CC, Freiburg A, Millevoi S, Stier G, Sorimachi H, Pelin K, Carrier L, Schwartz K, Labeit D, Gregorio CC, Linke WA, Labeit S , Rev Physiol Biochem Pharmacol (1999) , 138 : 19-55 (Review) - Mechanically driven contour-length adjustment in rat cardiac titin's unique N2B sequence: titin is an adjustable spring
Helmes M, Trombitás K, Centner T, Kellermayer M, Labeit S, Linke WA, Granzier H , Circ Res (1999) , 84(11) : 1339-52
- A spring tale: new facts on titin elasticity
Linke WA, Granzier H , Biophys J (1998) , 75(6) : 2613-4 - Nature of PEVK-titin elasticity in skeletal muscle
Linke WA, Ivemeyer M, Mundel P, Stockmeier MR, Kolmerer B , Proc Natl Acad Sci U S A (1998) , 95(14) : 8052-7 - Characterizing titin's I-band Ig domain region as an entropic spring
Linke WA, Stockmeier MR, Ivemeyer M, Hosser H, Mundel P , J Cell Sci (1998) , 111 : 1567-74 - Striational autoantibodies in myasthenia gravis patients recognize I-band titin epitopes
Lübke E, Freiburg A, Skeie GO, Kolmerer B, Labeit S, Aarli JA, Gilhus NE, Wollmann R, Wussling M, Rüegg JC, Linke WA , J Neuroimmunol (1998) , 81(1-2) : 98-108 - Auf den Spuren molekularer Federn. Genetische und mechanische Analyse des Muskelproteins Titin
Linke WA, Labeit S, Rüegg JC , Physiologie. Deutsche Physiologische Gesellschaft (P. Scheid., Ed.) (1998) , 10 : 13-17
- Actin-titin interaction in cardiac myofibrils: probing a physiological role
Linke WA, Ivemeyer M, Labeit S, Hinssen H, Rüegg JC, Gautel M , Biophys J (1997) , 73(2) : 905-19 - Tissue-specific expression and alpha-actinin binding properties of the Z-disc titin: implications for the nature of vertebrate Z-discs
Sorimachi H, Freiburg A, Kolmerer B, Ishiura S, Stier G, Gregorio CC, Labeit D, Linke WA, Suzuki K, Labeit S , J Mol Biol (1997) , 270(5) : 688-95 - Basis of passive tension and stiffness in isolated rabbit myofibrils
Bartoo ML, Linke WA, Pollack GH , Am J Physiol (1997) , 273(1 Pt 1) : C266-76 - The giant protein titin. Emerging roles in physiology and pathophysiology
Labeit S, Kolmerer B, Linke WA , Circ Res (1997) , 80(2) : 290-4 (Review)
- Towards a molecular understanding of the elasticity of titin
Linke WA, Ivemeyer M, Olivieri N, Kolmerer B, Rüegg JC, Labeit S , J Mol Biol (1996) , 261(1) : 62-71 - Limits of titin extension in single cardiac myofibrils
Linke WA, Bartoo ML, Ivemeyer M, Pollack GH , J Muscle Res Cell Motil (1996) , 17(4) : 425-38
- Passive and active tension in single cardiac myofibrils
Linke WA, Popov VI, Pollack GH , Biophys J (1994) , 67(2) : 782-92
- Spontaneous sarcomeric oscillations at intermediate activation levels in single isolated cardiac myofibrils
Linke WA, Bartoo ML, Pollack GH , Circ Res (1993) , 73(4) : 724-34
- Membrane Remodeling by a Bacterial Phospholipid-Methylating Enzyme.
Research Projects
Sarcomere: unit structure of muscle
A molecular approach to diastolic heart failure
Ongoing studies at the Ruhr University, Germany, are seeking new targets in the fight against diastolic heart failure. The researchers are shedding light on the elasticity of heart muscle cells.
Professor Wolfgang A. Linke is conducting groundbreaking research into titin, a large protein prevalent in the human body. Here, he talks about his 20 years’ experience in the field.
Flyer made by ResearchMedia:
International Innovation is the leading global dissemination resource for the wider scientific, technology and research communities, dedicated to disseminating the latest science, research and technological innovations on a global level. More information and a complimentary subscription offer to the publication can be found at: www.researchmedia.euTitin Research Roundup
Titin is a high-molecular weight protein (3.0-3.8 MDa) in the sarcomeres of vertebrate striated muscles. A plethora of titin isoforms is expressed from the copy of a single titin gene (on chromosome 2 in mouse and humans).
Mechanics of the Single Myofibril
The single myofibril is the minimum preparation that retains the natural architecture of the sarcomere. As such, it has some important advantages over the larger preparations that also retain the lattice.
Physiology of Cardiac and Skeletal Muscle
Recent investigations using quantitative RT-PCR and high-resolution SDS-polyacrylamide gel electrophoresis showed that the titin isoform expression pattern is modified dramatically during perinatal heart development (Opitz et al., 2004).
Cell Biology of Vertebrate and Invertebrate Muscle
We are interested in finding out how titin or titin-like proteins act together with actin, myosin, and many other cytoskeletal proteins to perform the important tasks of scaffolding, mechanical sensing and force generation.
Molecular Biophysics: Titin (AFM mechanics), Actin, Myosin
Single-Molecule Atomic Force Microscopy of Titin
Actin-Myosin in-vitro Motility AssayResearch Projects
- Titin Research Roundup
- Mechanics of the Single Myofibril
- Physiology of Cardiac and Skeletal Muscle
- Cell Biology of Vertebrate and Invertebrate Muscle
- Molecular Biophysics: Titin (AFM mechanics), Actin, Myosin
Some other titin pages
- Titin Research Roundup
Archiv - Pressemitteilungen
12.10.2017: Posterpreis für Melissa Herwig
Auf der Herztagung 2017 der Deutschen Gesellschaft für Kardiologie in Berlin gehörte Melissa Herwig aus der Kardiovaskulären Physiologie zu den Posterpreisgewinnern.
Postertitel: Impact of cGMP-PKG Pathway Modulation on Titin Phosphorylation and Titin-Based Myocardial Passive Stiffness.
Melissa Herwig, Soraya Hölper, Marcus Krüger, Doris Koesling, Michaela Kuhn, Wolfgang A Linke, Nazha Hamdani
Unterstützt wird das Projekt durch FORUM RUB und DFG.
Foto01.06.2017: The challenge of treating a stiff heart
Interview with Dr Nazha Hamdani in "Research Features", Issue 109
article
Research Features30.03.2017: Seltene Muskelkrankheit entdeckt
Andreas Unger und Matthias Vorgerd erforschen gemeinsam die Ursachen der muskulären BICD2-Krankheit. Nach der Ursache für diese Krankheit mussten die Bochumer Mediziner gründlich suchen. Und auch jetzt sind noch viele Fragen zu den zugrunde liegenden Mechanismen offen. RUB-News Wissenschaft (Rubin, 02.05.2017)09.02.2016: Protein Titin hilft, ein paar Kilogramm mehr zu stemmen
Titin, das größte Protein im menschlichen Körper, ist für die Elastizität der Muskeln entscheidend – und für noch mehr, fanden Forscher nun heraus. Ohne Titin könnten unsere Muskeln ein paar Kilogramm weniger stemmen.
Presseinformation der RUB21.11.2015: Forschungspreis der Deutschen Duchenne Stiftung
für Prof. Dr. M. Vorgerd and Dr. A. Unger
für das Projekt
„Die Bedeutung der Hitzeschockproteine für die Muskeldystrophie Duchenne genauer zu untersuchen, um besser die Muskelbiopsien der Patienten mit Muskeldystrophie Duchenne im Vergleich zu Kontrollproben zu verstehen, mit Ziel auf Therapieoptionen zu finden“
WAZ Bochum, 23.11.2015
Preisübergabe28.08.2015: Herzerkrankung besser verstehen
Ob und wie schwer Patienten an der Herzschwäche „Dilatative Kardiomyopathie“ erkranken, hängt offenbar davon ab, in welchem Teil des sogenannten Titinmoleküls eine Mutation vorliegt.
Presseinformation der RUB27.04.2015: Stromausfall: Schaden für die Forschung noch nicht abzusehen
Rund 20 Stunden Stromausfall haben am 15. und 16. April den Betrieb auf dem RUB-Campus nahezu komplett lahmgelegt. Welchen Schaden das in der Forschung ausgelöst hat, ist noch längst nicht abzusehen. Für viele Wissenschaftlerinnen und Wissenschaftler war nicht „stromfrei“ angesagt, sondern eine Nachtschicht.
Zum Bericht, auch aus unserem Institut ...10.10.2014: Interview mit Prof. Linke im ORF 1
Zur Therapie gegen diastolische Herzschwäche wurde im Österreichischen Rundfunk im Rahmen des Programms "Dimensionen - die Welt der Wissenschaft" ein Beitrag mit Prof. Linke gesendet.
Hier die Ankündigung auf der Webseite des Senders und der Beitrag als .mp3-Datei.ORF1 Ankündigung.pdf (51.9 kB)
ORF1_Beitrag.mp3 (ca. 7 min) (4.1 MB)
29.09.2014: Weltherztag
Für die RUB-Serie "Heute im Blick" zu verschiedenen Aktionstagen wurde Prof. Wolfgang Linke zum heutigen "Weltherztag" interviewt.
Presseinformation der RUB19.03.2014: Wie Herzmuskelzellen ihre Elastizität regulieren
Forscherteam entdeckt Mechanismen zur Kontrolle der Steife des Herzmuskels.
Akutes Herzversagen kann Federregion des Riesenproteins Titin dauerhaft schädigen.
Presseinformation der RUB03.02.2014: Prof. Linke im Interview bei J Cell Biol
Im Zusammenhang mit der neuesten Veröffentlichung im J Cell Biol entstand ein Kurzinterview mit Prof. Linke.
Hier der Biobytes-Podcast.
Publikation: Human myocytes are protected from titin aggregation-induced stiffening by small heat shock proteins.12.04.2013: Franz-Maximilian-Groedel-Forschungspreis 2013
Für ihre Gemeinschaftsarbeit wurde Prof. Dr. Wolfgang Linke und Dr. Nazha Hamdani auf der Eröffnungsveranstaltung der Jahrestagung der DKG in Mannheim der Franz-Maximilian-Groedel-Forschungspreis verliehen.
Mehr...
Deutsche Gesellschaft für Kardiologie – Herz- und Kreislaufforschung e.V.15.03.2013: Molekularer Ansatz der diastolischen Herzinsuffizienz
Laufende Studien an der Ruhr-Universität Bochum suchen nach neuen Zielen im Kampf gegen die diastolische Herzinsuffizienz. Die Forscher geben Aufschluss über die Elastizität der Herzmuskelzellen.
Flyer14.01.2013: Das hält das Herz elastisch
Enzym CaM-Kinase II entspannt die Muskelzellen. RUB-Forscher finden überaktives Enzym in insuffizienten Herzen.
Pressemitteilung der RUB21.11.2012: Titin - Bandwurmwort füllt dreieinhalbstündiges Video
Ein Russe liest das angeblich längste Wort in englischer Sprache - die Aminosäureabfolge eines Proteins (Titin). Er braucht dafür 3,5 Stunden.
Artikel Spiegel-Online18.01.2012 : Wie Proteinnetzwerke Muskelfasern stabilisieren
Gleicher Mechanismus für Muskelproteine wie für DNA gefunden
Forscherteam mit RUB-Beteiligung (Prof. Linke) berichtet in Genes and Development
Pressemitteilung der RUB21.12.2011 : Viagra gegen Herzinsuffizienz
Circulation: Wirkstoff Sildenafil macht versteifte Herzwände wieder elastisch
Forscher der RUB (Prof. Linke) und aus Rochester klären Wirkmechanismus auf
Pressemitteilung der RUB
Auswahl anderer Presse-Informationen14.12.2010 : EU-Förderung (FP7) für MEDIA
Wie Fett dem Herz schadet: Der Diastolischen Herzinsuffizienz auf der Spur
Prof. Linke ist Vizekoordinator des Projekts, das den Ursachen der Diastolischen Herzinsuffizienz auf den Grund geht.
Pressemitteilung der RUBDez. 2004: Titan Titin - Herzmuskelforschung in Münster
Laborjournal: Titin ist mit 3-4 Megadalton ein Gigant unter den Proteinen. Nach Myosin udn Aktin ist es dritthäufigster Proteinbestandteil im Skelett- und Herzmuskel. Die Gruppe um Wolfgang Linke beschäftigt sich mit Funktion und Isoformen des Titins, insbesondere dessen Rollen bei Entwicklung und Erkrankungen des Herzens.
Titan Titin