Professor Metin Avkiran BSc PhD DSc FISHR
Professor of Molecular Cardiology
The Rayne Institute
4th Floor, Lambeth Wing
St Thomas' Hospital
Westminster Bridge Road
London SE1 7EH
Email: metin.avkiran@kcl.ac.uk
Biography
Professor Avkiran obtained his BSc Hons in Pharmacology (1983) and PhD in Cardiovascular Pharmacology (1987) from the University of Bath. In 2002, he was awarded a DSc by the same University, in recognition of his published research on the cardiac Na+/H+ exchanger. Professor Avkiran has held various research and academic appointments at UMDS and subsequently King's College London since 1987, including a 10-year Basic Science Lectureship/Senior Lectureship Award from the British Heart Foundation. He was appointed as Professor of Molecular Cardiology at King's College London in 2001.
Professor Avkiran is currently the President Elect of the International Society for Heart Research (ISHR), which he has previously served as Secretary General for consecutive terms (2004-2007, 2007-2010). He has also served as the Secretary (1996-1998) and Chairman (2000-2002) of the British Society for Cardiovascular Research (BSCR), as a member of the ISHR European Section Council (1995-2001) and the ISHR World Council (2001-2004), and as the Chairman of the Myocardial Biology Panel of the British Cardiac Society (BCS). In 2000, he was the recipient of the prestigious Pfizer Award in Biology (in recognition of his work on the cardiac Na+/H+ exchanger) and an invited member of the National Institutes of Health (USA) Panel on Myocardial Resuscitation. More recently, he received the 2012 Keith Reimer Distinguished Lecture Award of the ISHR.
He is currently an Associate Editor of the
Journal of Molecular and Cellular Cardiology and serves on the Editorial Boards of
Basic Research in Cardiology, Cardiovascular Research, Dialogues in Cardiovascular Medicine and the Journal of Physiology. He has previously served as an Associate Editor of
Cardiovascular Research (1991-1995) and
Pharmacology & Therapeutics (2001-2005) and on the Editorial Boards of
Circulation (2000-2004),
Journal of Molecular and Cellular Cardiology (1999-2011)
and the
British Journal of Pharmacology (2002-2005). Professor Avkiran was Chairman of the Scientific Programme Committees of the XIX ISHR World Congress in 2007 (Bologna, Italy) and the XX ISHR World Congress in 2010 (Kyoto, Japan).
Research interests
Professor Avkiran’s Molecular Cardiology Group aims to integrate physiological and pharmacological approaches with biochemical and molecular biological techniques to study mechanisms underlying cardiac injury and dysfunction (e.g. arrhythmias, contractile dysfunction, infarction), particularly in the contexts of ischaemic heart disease and heart failure, and to develop and evaluate novel interventions for the inhibition and/or reversal of such injury and dysfunction. Current work is focused on (i) cardiac signalling by G protein-coupled receptors and downstream transduction pathways, with emphasis on protein kinases (PKC, PKD, ERK, p90RSK) and phosphatases (PP2A), and (ii) the pathophysiological roles and molecular regulation of the cardiac sarcolemmal Na+/H+ exchanger (NHE) and the therapeutic potential of novel NHE inhibitors.
The Group’s work involves the complementary use of a variety of techniques such as myocyte isolation, cell culture, DNA manipulation and in vitro gene transfer, microepifluorescence, immunocytohemistry and confocal microscopy, kinase assays and other protein biochemistry methods, and the study of cardiac ischaemic injury and contractile dysfunction in experimental systems, including isolated tissues and hearts and transgenic models.
Novel PKD substrates in the cardiac sarcomere, identified by the Group.
Group members
RCUK Fellow
Postdoctoral Fellows
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Dr S Bardswell
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Dr A Candasamy
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Dr K Stathopoulou
BHF Centre Core Scientist
PhD Student
Research Technician
Selected publications
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Haworth RS, Stathopoulou K, Candasamy AJ, Avkiran M. Neurohormonal regulation of cardiac histone deacetylase 5 nuclear localization by phosphorylation-dependent and phosphorylation -independent mechanisms. Circ Res. 2012; 110:1585-1595
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Cuello F, Bardswell SC, Haworth RS, Ehler E, Sadayappan S, Kentish JC, Avkiran M. A novel role for p90 ribosomal S6 kinase in the regulation of cardiac myofilament phosphorylation. J Biol Chem. 2011; 286:5300-5310
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Haworth RS, Cuello F, Avkiran M.Regulation by phosphodiesterase isoforms of protein kinase A-mediated attenuation of myocardial protein kinase D activation. Basic Res Cardiol. 2011;106:51-63.
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Yin X, Cuello F, Mayr U, Hao Z, Hornshaw M, Ehler E, Avkiran M, Mayr M. Proteomics analysis of the cardiac myofilament subproteome reveals dynamic alterations in phosphatase subunit distribution. Mol Cell Proteom. 2010; 9:497-509.
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BardswellSC, Cuello F, Rowland AJ, Sadayappan S, Robbins J, GautelM, Walker JW, Kentish JC, Avkiran M. Distinct sarcomeric substrates are responsible for protein kinase D-mediated regulation of cardiac myofilament Ca2+ sensitivity and cross-bridge cycling. J Biol Chem. 2010 ;285:5674-5682.
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Cook AR, Bardswell SC, Pretheshan S, Dighe K, Kanaganayagam GS, Jabr RI, Merkle S, Marber MS, Engelhardt S, Avkiran M. Paradoxical resistance to myocardial ischemia and age-related cardiomyopathy in NHE1 transgenic mice: a role for ER stress? J Mol Cell Cardiol. 2009; 46:225-233.
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Snabaitis AK, Cuello F, Avkiran M. Protein kinase B/Akt phosphorylates and inhibits the cardiac Na+/H+ exchanger NHE1. Circ Res. 2008;103:881-890.
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Avkiran M, Rowland AJ, Cuello F, Haworth RS. Protein kinase D in the cardiovascular system: emerging roles in health and disease. Circ Res. 2008;102:157-63.
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Bossuyt J, Helmstadter K, Wu X, Clements-Jewery H, Haworth RS, Avkiran M, Martin JL, Pogwizd SM, Bers DM. Ca2+/calmodulin-dependent kinase II delta and protein kinase D overexpression reinforce the histone deacetylase 5 redistribution in heart failure. Circ Res. 2008;102:695-702.
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Cuello F, Bardswell SC, Haworth RS, Yin X, Lutz S, Wieland T, Mayr M, Kentish JC, Avkiran M. Protein kinase D selectively targets cardiac troponin I and regulates myofilament Ca2+ sensitivity in ventricular myocytes. Circ Res. 2007;100:864-873.
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Cuello F, Snabaitis AK, Cohen MS, Taunton J, Avkiran M. Evidence for direct regulation of myocardial NHE1 phosphorylation and activity by RSK: effects of the novel and specific RSK inhibitor fmk on responses to alpha1-adrenergic stimulation. Mol Pharmacol. 2007;71:799-806.
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Snabaitis AK, D'Mello R, Dashnyam S, Avkiran M. A novel role for protein phosphatase 2A in receptor-mediated regulation of the cardiac sarcolemmal Na+/H+ exchanger NHE1. J Biol Chem. 2006;281:20252-20262.
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Haworth RS, Cuello F, Herron TJ, Franzen G, Kentish JC, Gautel M, Avkiran M. Protein kinase D is a novel mediator of cardiac troponin I phosphorylation and regulates myofilament function. Circ Res. 2004;95:1091-1099.
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Aker S, Snabaitis AK, Konietzka I, Van de Sand A, Böngler K, Avkiran M, Heusch G, Schulz R. Inhibition of the Na+/H+ exchanger attenuates the deterioration in ventricular function during pacing-induced heart failure in rabbits. Cardiovasc Res. 2004;63:273-282.
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Haworth K, McCann C, Snabaitis AK , Roberts NA, Avkiran M. Stimulation of the plasma membrane Na+/H+ exchanger NHE1 by sustained intracellular acidosis: evidence for a novel mechanism mediated by the ERK pathway. J Biol Chem. 2003;278:31676-31684.
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Avkiran M, Marber MS. Na+/H+ exchange inhibitors for cardioprotective therapy: progress, problems and prospects. J Am Coll Cardiol. 2002;39:747-753.
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Snabaitis AK, Hearse DJ, Avkiran M. Regulation of sarcolemmal Na+/H+ exchange by hydrogen peroxide in adult rat ventricular myocytes. Cardiovasc Res. 2002;53:470-480.
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Martin JL, Avkiran M, Quinlan RA, Cohen P, Marber MS. Anti-ischemic effects of SB203580 are mediated through the specific inhibition of p38 alpha-mitogen-activated protein kinase: Evidence from ectopic expression of an inhibition-resistant kinase. Circ Res. 2001;89:750-752.
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Yokoyama H, Gunasegaram S, Harding SE, Avkiran M. Sarcolemmal Na+/H+ exchanger activity and expression in human myocardium. J Am Coll of Cardiol. 2000;36:534-540.
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Snabaitis AK, Yokoyama H, Avkiran M. Roles of mitogen-activated protein kinases and protein kinase C in alpha1A-adrenoceptor-mediated stimulation of the sarcolemmal Na+/H+ exchanger. Circ Res. 2000;86:214-220.
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Haworth RS, Goss MW, Rozengurt E, Avkiran M. Expression and activity of protein kinase D/protein kinase C mu in myocardium: evidence for alpha1-adrenergic receptor- and protein kinase C-mediated regulation. J Mol Cell Cardiol. 2000;32:1013-1023.
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Avkiran M. Protection of the myocardium during ischemia and reperfusion: Na+/H+ exchange inhibition versus ischemic preconditioning. Circulation. 1999;100:2469-2472.
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Gunasegaram S, Haworth RS, Hearse DJ, Avkiran M. Regulation of sarcolemmal Na+/H+ exchanger activity by angiotensin II in rat ventricular myocytes: opposing actions via AT1 versus AT2 receptors. Circ Res. 1999;85:919-930.
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Yokoyama H, Yasutake M, Avkiran M. Alpha1-adrenergic stimulation of sarcolemmal Na+-H+ exchanger activity in rat ventricular myocytes: evidence for selective mediation by the alpha1A-adrenoceptor subtype. Circ Res. 1998;82:1078-1085.
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Shipolini AR, Yokoyama Y, Galinanes M, Edmondson SJ, Hearse DJ, Avkiran M. Na+/H+ exchanger activity does not contribute to protection by ischemic preconditioning in the isolated rat heart. Circulation. 1997;96:3617-3625.