Imperial College London

ProfessorSianHarding

Faculty of MedicineNational Heart & Lung Institute

Emeritus Professor of Cardiac Pharmacology
 
 
 
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Contact

 

+44 (0)20 7594 3009sian.harding Website

 
 
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Location

 

435ICTEM buildingHammersmith Campus

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Summary

 

Publications

Publication Type
Year
to

464 results found

Chen QZ, Harding SE, Rai R, Boccaccini ARet al., 2014, Myocardial tissue engineering, Tissue Engineering Using Ceramics and Polymers: Second Edition, Pages: 387-413, ISBN: 9780857097125

In the pursuit of engineering a functional myocardium, studies integrating highly innovative research in stem cells and biomaterials development have opened new frontiers. Stringent properties like biocompatibility, ability to foster cells, biodegradability and mechanical compliance have been the norm for material selection. Fabrication techniques implemented individually or in conjunction have been used to fabricate scaffolds that best mimic the anisotropic nature of the cardiac extracellular matrix (ECM). Such biomimetic scaffolds provide topographical cues for contact guidance to align cells required to achieve synchronous electrophysiological coupling of the engineered myocardium to the native heart. Various functionalization strategies in tandem with scaffold fabrication designs and bioreactor studies have been undertaken to achieve vascularization in the engineered cardiac construct.

Book chapter

Sikkel MB, Hayward C, MacLeod KT, Harding SE, Lyon ARet al., 2014, SERCA2a gene therapy in heart failure: an anti-arrhythmic positive inotrope, BRITISH JOURNAL OF PHARMACOLOGY, Vol: 171, Pages: 38-54, ISSN: 0007-1188

Journal article

Schobesberger S, Tokar S, Bhargava A, Wright P, Sikkel M, Mitra N, Monszpart A, Lyon A, Harding SE, Gorelik Jet al., 2013, Alteration in b2-ARs Dependent cAMP Signalling Linked to Post Infarction Remodelling of T-tubules in Rat Cardiomyocytes, Scientific Sessions and Resuscitation Science Symposium of the American-Heart-Association, Publisher: LIPPINCOTT WILLIAMS & WILKINS, ISSN: 0009-7322

Conference paper

Harding S, 2013, Heart failure therapy: drugs, genes or stem cells?: by Caroline Telfer., Future Cardiol, Vol: 9, Pages: 629-633

Professor Sian Harding talks to Caroline Telfer, Assistant Commissioning Editor. Professor Sian Harding obtained her PhD in Pharmacology from King's College, London (UK) in 1981. She became Professor of Cardiac Pharmacology at the National Heart and Lung Institute, a division of the Imperial College Faculty of Medicine, in 2002. Her work has been funded by the British Heart Foundation, the Wellcome Trust, the Medical Research Council, the Biochemical and Biophysical Research Council, the The National Centre for the Replacement, Refinement and Reduction of Animals in Research, Pfizer, GlaxoSmithKline and SmithKline Beecham. Harding is former president of the European Section of the International Society for Heart Research and has organized international cardiovascular science meetings for this society, as well as for the European Society of Cardiology. She is the principal investigator for the first UK gene therapy trial aimed at improving cardiac contractility, organized jointly at Harefield and Papworth Hospitals. Harding is a member of the Nuffield Council on Bioethics and the Medical Research Coucil Regenerative Medicine Research Committee, and Director of a recently awarded British Heart Foundation Cardiovascular Regenerative Medicine Centre. She has been elected Fellow of the American Heart Association, European Society of Cardiology, International Society for Heart Research, Society of Biology and British Society of Pharmacology.

Journal article

Song X, Xie M, Hofmann F, Jun TS, Connolley T, Reinhard C, Atwood RC, Connor L, Drakopoulos M, Harding S, Korsunsky AMet al., 2013, Residual stresses in Linear Friction Welding of aluminium alloys, Materials & Design, Vol: 50, Pages: 360-369, ISSN: 0261-3069

Journal article

Foldes G, Matsa E, Kriston-Vizi J, Leja T, Mioulane M, Vauchez K, Ketteler R, Schneider MD, Denning C, Harding SEet al., 2013, Key differences in hypertrophic signalling between hESC- and hIPSC-derived cardiomyocytes, Congress of the European-Society-of-Cardiology (ESC), Publisher: OXFORD UNIV PRESS, Pages: 279-279, ISSN: 0195-668X

Conference paper

Rees PSC, Davidson SM, Harding SE, McGregor C, Elliot PM, Yellon DM, Hausenloy DJet al., 2013, The Mitochondrial Permeability Transition Pore as a Target for Cardioprotection in Hypertrophic Cardiomyopathy, CARDIOVASCULAR DRUGS AND THERAPY, Vol: 27, Pages: 235-237, ISSN: 0920-3206

Journal article

Gorelik J, Wright PT, Lyon AR, Harding SEet al., 2013, Spatial control of the βAR system in heart failure: the transverse tubule and beyond, CARDIOVASCULAR RESEARCH, Vol: 98, Pages: 216-224, ISSN: 0008-6363

Journal article

Sikkel MB, Collins TP, Rowlands C, Shah M, O'Gara P, Williams AJ, Harding SE, Lyon AR, MacLeod KTet al., 2013, Triple mode of action of flecainide in catecholaminergic polymorphic ventricular tachycardia: reply, CARDIOVASCULAR RESEARCH, Vol: 98, Pages: 327-328, ISSN: 0008-6363

Journal article

Sikkel MB, Collins TP, Rowlands C, Shah M, OGara P, Williams AJ, Harding SE, Lyon AR, MacLeod KTet al., 2013, Flecainide reduces Ca<SUP>2+</SUP> spark and wave frequency via inhibition of the sarcolemmal sodium current, CARDIOVASCULAR RESEARCH, Vol: 98, Pages: 286-296, ISSN: 0008-6363

Journal article

Sikkel M, Rowlands C, Harding S, Lyon A, MacLeod Ket al., 2013, REDUCING SARCOLEMMAL SODIUM CURRENT DECREASES SPONTANEOUS SR CA2+RELEASE, Annual Conference of the British-Cardiovascular-Society (BCS), Publisher: BMJ PUBLISHING GROUP, Pages: A120-A120, ISSN: 1355-6037

Conference paper

Mills A, Harding S, Lyon A, Sikkel M, Thum T, Kumarswamy Ret al., 2013, MiR-1 and SERCA2a gene therapy in the failing heart, Conference of the British-Society-for-Gene-and-Cell-Therapy (BSGCT), Publisher: MARY ANN LIEBERT INC, Pages: A34-A34, ISSN: 1043-0342

Conference paper

Foldes G, Matsa E, Kriston-Vizi J, Leja T, Amisten S, Kolker L, Mioulane M, Vauchez K, Aranyi T, Ketteler R, Schneider M, Denning C, Harding Set al., 2013, Key differences in hypertrophic signalling in hESC-and hIPSC-derived cardiomyocytes, Conference of the British-Society-for-Gene-and-Cell-Therapy (BSGCT), Publisher: MARY ANN LIEBERT INC, Pages: A9-A9, ISSN: 1043-0342

Conference paper

Khan JM, Lyon AR, Harding SE, 2013, The case for induced pluripotent stem cell-derived cardiomyocytes in pharmacological screening, BRITISH JOURNAL OF PHARMACOLOGY, Vol: 169, Pages: 304-317, ISSN: 0007-1188

Journal article

Reed DM, Kirkby NS, Foldes G, Gashaw HH, Randi AM, Starke RD, Paschalaki KE, Harding SE, Mitchell JAet al., 2013, Prostacyclin release pathways in stem cell derived endothelial cells, Experimental Biology 2013

Conference paper

Reed DM, Foldes G, Gashaw HH, Harding SE, Mitchell JAet al., 2013, Conditioning of human embryonic stem cell-derived endothelial cells with PBMCs confers TLR4 sensing in co-culture conditions, Experimental Biology 2013

Conference paper

Gillis RB, Adams GG, Wolf B, Berry M, Besong TMD, Corfield A, Kok SM, Sidebottom R, Lafond D, Rowe AJ, Harding SEet al., 2013, Molecular weight distribution analysis by ultracentrifugation: Adaptation of a new approach for mucins, 2nd International Polysaccharide Conference on Polysaccharides as Source of Advanced and Sustainable Products (EPNOE), Publisher: ELSEVIER SCI LTD, Pages: 178-183, ISSN: 0144-8617

Conference paper

Rao C, Prodromakis T, Kolker L, Chaudhry UAR, Trantidou T, Sridhar A, Weekes C, Camelliti P, Harding SE, Darzi A, Yacoub MH, Athanasiou T, Terracciano CMet al., 2013, The effect of microgrooved culture substrates on calcium cycling of cardiac myocytes derived from human induced pluripotent stem cells, Biomaterials, Vol: 34, Pages: 2399-2411, ISSN: 0142-9612

Induced pluripotent stem cell-derived cardiomyocytes (iPSC-CM) have been widely proposed as in vitro models of myocardial physiology and disease. A significant obstacle, however, is their immature phenotype. We hypothesised that Ca2+ cycling of iPSC-CM is influenced by culture conditions and can be manipulated to obtain a more mature cellular behaviour. To test this hypothesis we seeded iPSC-CM onto fibronectin coated microgrooved polydimethylsiloxane (PDMS) scaffolds fabricated using photolithography, or onto unstructured PDMS membrane. After two weeks in culture, the structure and function of iPSC-CM were studied. PDMS microgrooved culture substrates brought about cellular alignment (p < 0.0001) and more organised sarcomere. The Ca2+ cycling properties of iPSC-CM cultured on these substrates were significantly altered with a shorter time to peak amplitude (p = 0.0002 at 1 Hz), and more organised sarcoplasmic reticulum (SR) Ca2+ release in response to caffeine (p < 0.0001), suggesting improved SR Ca2+ cycling. These changes were not associated with modifications in gene expression. Whilst structured tissue culture may make iPSC-CM more representative of adult myocardium, further construct development and characterisation is required to optimise iPSC-CM as a model of adult myocardium.

Journal article

Roether JA, Jawad H, Rai R, Ali NN, Harding SE, Boccaccini ARet al., 2013, Polymers for Myocardial Tissue Engineering, POLYMERIC BIOMATERIALS: MEDICINAL AND PHARMACEUTICAL APPLICATIONS, VOL 2, Editors: Popa, Publisher: CRC PRESS-TAYLOR & FRANCIS GROUP, Pages: 369-388, ISBN: 978-1-4200-9468-8

Book chapter

Wright PT, Diakonov I, Nikolaev VO, Lyon AR, Harding SE, Gorelik Jet al., 2012, Myocardial Gradients in Caveolar Number Modulate Cardiomyocyte Contractile Response to Specific β2AR Stimulation, CIRCULATION, Vol: 126, ISSN: 0009-7322

Journal article

Wright PT, Nikolaev VO, Tokar S, Bhargava A, Diakonov I, Sikkel MB, Lyon AR, Harding SE, Gorelik Jet al., 2012, Caveolin3 Depletion Modifies β2AR-cAMP Responses at Both Cellular and Sub-Cellular Levels in Cardiomyocytes, CIRCULATION, Vol: 126, ISSN: 0009-7322

Journal article

Mioulane M, Foldes G, Ali NN, Schneider MD, Harding SEet al., 2012, Development of high content imaging methods for cell death detection in human pluripotent stem cell-derived cardiomyocytes, Journal of Cardiovascular Translational Research, Vol: 5, Pages: 593-604, ISSN: 1937-5387

Human pluripotent stem cell-derived cardiomyocytes (hPSC-CM) are being investigated as a new source of cardiac cells for drug safety assessment. We developed a novel scalable high content microscopy-based method for the detection of cell death in hPSC-CM that can serve for future predictive in vitro cardio-toxicological screens. Using rat neonatal ventricular cardiomyocytes (RVNC) or hPSC-CM, assays for nuclear remodelling, mitochondrial status, apoptosis and necrosis were designed using a combination of fluorescent dyes and antibodies on an automated microscopy platform. This allowed the observation of a chelerythrine-induced concentration-dependent apoptosis to necrosis switch and time-dependent progression of early apoptotic cells towards a necrotic-like phenotype. Susceptibility of hPSC-CM to chelerythrine-stimulated apoptosis varied with time after differentiation, but at most time points, hPSC-CM were more resistant than RVNC. This simple and scalable humanized high-content assay generates accurate cardiotoxicity profiles that can serve as a base for further assessment of cardioprotective strategies and drug safety.

Journal article

Harding SE, 2012, Frontiers in cardiovascular biology: London 2012 - a scientific 'olympiad'., Future Cardiol, Vol: 8, Pages: 689-691

Imperial College London (UK) was the showcase for the second in the 'Frontiers in Cardiovascular Biology' series, a biennial meeting of the European Society of Cardiology Council on basic cardiovascular sciences, held from 30 March to 1 April 2012. The aim of this series is to bring researchers together to learn the very latest findings in cardiac and vascular sciences, and to see state-of-the-art and developing technologies that could impact cardiovascular research. Five keynote lectures, 25 scientific symposia and two translational lunchtime symposia were grouped around the central themes of bioimaging, degeneration and regeneration, and inflammation.

Journal article

Paur H, Wright PT, Sikkel MB, Tranter MH, Mansfield C, O'Gara P, Stuckey DJ, Nikolaev VO, Diakonov I, Pannell L, Gong H, Sun H, Peters NS, Petrou M, Zheng Z, Gorelik J, Lyon AR, Harding SEet al., 2012, High levels of circulating epinephrine trigger apical cardiodepression in a β2-adrenergic receptor/Gi-dependent manner: a new model of Takotsubo cardiomyopathy., Circulation Journal, Vol: 6, Pages: 697-706

Journal article

Mioulane M, Foldes G, Harding S, 2012, Cardiomyocytes from Human Pluripotent Stem Cells Predict Chemotherapy-Induced Cardiotoxicity, Basic Cardiovascular Sciences Scientific Session, Publisher: LIPPINCOTT WILLIAMS & WILKINS, ISSN: 0009-7330

Conference paper

Sikkel MB, Collins TP, O'Gara P, Harding SE, Lyon AR, Macleod KTet al., 2012, Elemental SR Ca2+release in failing human cardiomyocytes - a comparison with failing rat cardiomyocytes and inhibition by flecainide, Congress of the European-Society-of-Cardiology (ESC), Publisher: OXFORD UNIV PRESS, Pages: 1045-1045, ISSN: 0195-668X

Conference paper

Reed DM, Foldes G, Harding SE, Mithcell JAet al., 2012, Stem cell derived endothelial cells for cardiovascular disease; a therapeutic perspective., British Journal of Clinical Pharmacology

Journal article

Wright PT, Pannell LMK, Nikolaev VO, Lyon AR, Harding SE, Gorelik Jet al., 2012, Imaging regional differences in beta-2 adrenergic receptor function at the cellular level, BSCR/BAS Joint Spring Meeting

Conference paper

Shah M, Sikkel MB, Desplantez T, Collins TP, Gara PO, Harding SE, Lyon AR, Macleod KTet al., 2012, Flecainide reduces calcium transient amplitude in rat cardiomyocytes with an absence of a significant reduction in l-type calcium current, 2nd Congress of the European-Society-of-Cardiology Council on Basic Cardiovascular Science - Frontiers in Cardiovascular Biology, Publisher: OXFORD UNIV PRESS, Pages: S108-S108, ISSN: 0008-6363

Conference paper

Foldes G, Bagyura Z, Lendvai Z, Mathe D, Nemeth T, Skopal J, Foldes I, Merkely B, Harding SEet al., 2012, Transplantation of human embryonic stem cell-derived endothelial cells into rats: a new approach for vascular regeneration, 2nd Congress of the European-Society-of-Cardiology Council on Basic Cardiovascular Science - Frontiers in Cardiovascular Biology, Publisher: OXFORD UNIV PRESS, Pages: S16-S17, ISSN: 0008-6363

Conference paper

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