糖心原创

School of Life Sciences
 

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Steven Charlton

Professor of Molecular Pharmacology and Drug Discovery, Faculty of Medicine & Health Sciences

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Biography

Prof Charlton joined the 糖心原创 in 2014 where he is Professor of Molecular Pharmacology and Drug Discovery in the School of Life Sciences. Prior to that he spent 16 years in the pharmaceutical industry, both at SmithKline Beecham and Novartis. At Novartis he was Director of Molecular Pharmacology in Respiratory Diseases, leading an assay development and compound profiling team of over 30 scientists providing expert opinion and support for GPCR, ion channel and enzyme projects. He has broad drug discovery experience, ranging from target validation through to leading full lead optimisation programmes to successful clinical proof of concept. He also served on global development teams for several inhaled compounds in Ph2, Ph3 and post-launch, including Onbrez鈩�, Seebri鈩� and UltiBro鈩�. In 2007 Prof Charlton was awarded Novartis Leading Scientist in recognition of his contribution to the field of quantitative pharmacology and to the Novartis pipeline. Prof Charlton is also Founder and Chief Scientific Officer of Excellerate Biosiences Ltd, a contract research organsiation that provides specialist molecular and cellular pharmacology solutions to the biotech and pharma sector.

Research Summary

Prof Charlton has research interests in two key areas:

Molecular Pharmacology

Prof Charlton is interested in all aspects of the quantitative assessment of ligand-receptor interactions, with particular expertise in the kinetics of ligand binding and signalling. His current research areas include:

  1. Developing novel higher throughput methodologies to quantify kinetic rate constants for binding of drugs to proteins. Main focus is GPCRs but also tackling protein-protein interactions and soluble enzymes
  2. Investigating biased signaling at GPCRs by investigating spatiotemporal signaling at a single cell and subcellular level using fluorescent and luminescent biosensors
  3. Measuring the concentration of drugs at a sub-cellular level to determine the influence of physchem properties and rebinding on observed pharmacology (e.g. kinetics and biased agonism)

Drug Discovery

The main drug discovery focus of the group is the identification of novel therapies to treat remodelling diseases, particularly in the airways (e.g. IPF, PAH, severe asthma and COPD). Prof Charlton's team has expertise in the culture of primary human structural cells from the lung (e.g. lung fibroblasts and smooth muscle cells from both the airway and pulmonary vasculature) and employs both phenotypic and pathway assays in a chemical-biology approach to identify targets capable of preventing or reversing key aspects of tissue remodelling.

Recent Publications

  • KOZICZAK-HOLBRO, MAGDALENA, RIGEL, DEAN F., DUMOTIER, BERENGERE, SYKES, DAVID A., TSAO, JEFFREY, NGOC-HONG NGUYEN, BOSCH, JULIAN, JOURDAIN, MARIE, FLOTTE, LUDIVINE, ADACHI, YUICHIRO, KIFFE, MICHAEL, AZRIA, MOISE, FAIRHURST, ROBIN A., CHARLTON, STEVEN J., RICHARDSON, BRIAN P., LACH-TRIFILIEFF, ESTELLE, GLASS, DAVID J., ULLRICH, THOMAS and HATAKEYAMA, SHINJI, 2019. JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS. 369(2), 188-199
  • SYKES, DAVID A., JAIN, PALASH and CHARLTON, STEVEN J., 2019. MOLECULAR PHARMACOLOGY. 96(3), 378-392
  • GHERBI, KAROLINA, BRIDDON, STEPHEN J. and CHARLTON, STEVEN J., 2018. SCIENTIFIC REPORTS. 8,
  • MICHEL, MARTIN C. and CHARLTON, STEVEN J., 2018. MOLECULAR PHARMACOLOGY. 93(4), 259-265
  • KOZICZAK-HOLBRO, MAGDALENA, RIGEL, DEAN F., DUMOTIER, BERENGERE, SYKES, DAVID A., TSAO, JEFFREY, NGOC-HONG NGUYEN, BOSCH, JULIAN, JOURDAIN, MARIE, FLOTTE, LUDIVINE, ADACHI, YUICHIRO, KIFFE, MICHAEL, AZRIA, MOISE, FAIRHURST, ROBIN A., CHARLTON, STEVEN J., RICHARDSON, BRIAN P., LACH-TRIFILIEFF, ESTELLE, GLASS, DAVID J., ULLRICH, THOMAS and HATAKEYAMA, SHINJI, 2019. JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS. 369(2), 188-199
  • SYKES, DAVID A., JAIN, PALASH and CHARLTON, STEVEN J., 2019. MOLECULAR PHARMACOLOGY. 96(3), 378-392
  • GHERBI, KAROLINA, BRIDDON, STEPHEN J. and CHARLTON, STEVEN J., 2018. SCIENTIFIC REPORTS. 8,
  • MICHEL, MARTIN C. and CHARLTON, STEVEN J., 2018. MOLECULAR PHARMACOLOGY. 93(4), 259-265
  • SYKES, DAVID A, LANE, J ROBERT, SZABO, MONIKA, CAPUANO, BEN, JAVITCH, JONATHAN A and CHARLTON, STEVEN J, 2018. Nature communications. 9(1), 3568
  • CIVCIRISTOV S, ELLISDON AM, SUDERMAN R, PON CK, EVANS BA, KLEIFELD O, CHARLTON SJ, HLAVACEK WS, CANALS M and HALLS ML, 2018. Science signaling. 11(551),
  • ROSETHORNE, ELIZABETH M and CHARLTON, STEVEN J, 2018. Airway remodeling disease: primary human structural cells and phenotypic and pathway assays to identify targets with potential to prevent or reverse remodeling. Journal of experimental pharmacology. 10, 75-85
  • SYKES, DAVID A. and CHARLTON, STEVEN J., 2018. RATIONAL DRUG DESIGN: METHODS AND PROTOCOLS. 1824, 177-194
  • SANDHAM DA, BARKER L, BROWN L, BROWN Z, BUDD D, CHARLTON SJ, CHATTERJEE D, COX B, DUBOIS G, DUGGAN N, HALL E, HATTO J, MAAS J, MANINI J, PROFIT R, RIDDY D, RITCHIE C, SOHAL B, SHAW D, STRINGER R, SYKES DA, THOMAS M, TURNER KL, WATSON SJ, WEST R, WILLARD E, WILLIAMS G and WILLIS J, 2017. ACS medicinal chemistry letters. 8(5), 582-586
  • SYKES DA, MOORE H, STOTT L, HOLLIDAY N, JAVITCH JA, LANE JR and CHARLTON SJ, 2017. Nature communications. 8(1), 763
  • BERGSDORF, CHRISTIAN, FIEZ-VANDAL, CEDRIC, SYKES, DAVID A., BERNET, PASCAL, AUSSENAC, SONIA, CHARLTON, STEVEN J., SCHOPFER, ULRICH, OTTL, JOHANNES and DUCKELY, MYRIAM, 2016. JOURNAL OF BIOMOLECULAR SCREENING. 21(3), 243-251
  • ROSETHORNE EM, BRADLEY ME, GHERBI K, SYKES DA, SATTIKAR A, WRIGHT JD, RENARD E, TRIFILIEFF A, FAIRHURST RA and CHARLTON SJ, 2016. Molecular pharmacology. 89(4), 467-75
  • KLEIN HERENBRINK C, SYKES DA, DONTHAMSETTI P, CANALS M, COUDRAT T, SHONBERG J, SCAMMELLS PJ, CAPUANO B, SEXTON PM, CHARLTON SJ, JAVITCH JA, CHRISTOPOULOS A and LANE JR, 2016. Nature communications. 7, 10842
  • SYKES DA, BRADLEY ME, RIDDY DM, WILLARD E, REILLY J, MIAH A, BAUER C, WATSON SJ, SANDHAM DA, DUBOIS G and CHARLTON SJ, 2016. Molecular pharmacology. 89(5), 593-605
  • DICKSON CJ, HORNAK V, VELEZ-VEGA C, MCKAY DJ, REILLY J, SANDHAM DA, SHAW D, FAIRHURST RA, CHARLTON SJ, SYKES DA, PEARLSTEIN RA and DUCA JS, 2016. Journal of medicinal chemistry. 59(12), 5780-9
  • BRADLEY, M. E., DOMBRECHT, B., MANINI, J., WILLIS, J., VLERICK, D., DE TAEYE, S., VAN DEN HEEDE, K., ROOBROUCK, A., GROT, E., KENT, T. C., LAEREMANS, T., STEFFENSEN, S., VAN HEEKE, G., BROWN, Z., CHARLTON, S. J. and CROMIE, K. D., 2015. MOLECULAR PHARMACOLOGY. 87(2), 251-262
  • VAUQUELIN, GEORGES, HALL, DAVID and CHARLTON, STEVEN J., 2015. BRITISH JOURNAL OF PHARMACOLOGY. 172(9), 2300-2315
  • ROSETHORNE EM, BRADLEY ME, KENT TC and CHARLTON SJ, 2015. Pharmacology research & perspectives. 3(1), e00101
  • TRIFILIEFF A, ETHELL BT, SYKES DA, WATSON KJ, COLLINGWOOD S, CHARLTON SJ and KENT TC, 2015. Toxicology and applied pharmacology. 287(1), 9-16
  • BLAKELEY D, SYKES DA, ENSOR P, BERTRAN E, ASTON PJ and CHARLTON SJ, 2015. British journal of pharmacology. 172(21), 5037-49
  • BERGSDORF C, FIEZ-VANDAL C, SYKES DA, BERNET P, AUSSENAC S, CHARLTON SJ, SCHOPFER U, OTTL J and DUCKELY M, 2015. Journal of biomolecular screening. 21(3), 243-51
  • DALE, PHILIPPA R., CERNECKA, HANA, SCHMIDT, MARTINA, DOWLING, MARK R., CHARLTON, STEVEN J., PIEPER, MICHAEL P. and MICHEL, MARTIN C., 2014. CURRENT OPINION IN PHARMACOLOGY. 16, 31-42
  • MACKENZIE, AMANDA E., CALTABIANO, GIANLUIGI, KENT, TOBY C., JENKINS, LAURA, MCCALLUM, JENNIFER E., HUDSON, BRIAN D., NICKLIN, STUART A., FAWCETT, LINDSAY, MARKWICK, RACHEL, CHARLTON, STEVEN J. and MILLIGAN, GRAEME, 2014. MOLECULAR PHARMACOLOGY. 85(1), 91-104
  • SANDHAM, DAVID A., CHARLTON, STEVEN J., DUBOIS, GERALD, ERPENBECK, VEIT J., SYKES, DAVID and WATSON, SIMON J., 2014. Discovery and characterisation of CRTh2 receptor antagonists suitable for clinical testing in allergic diseases ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY. 248,
  • BILL, ANKE, ROSETHORNE, ELIZABETH M., KENT, TOBY C., FAWCETT, LINDSAY, BURCHELL, LYNN, VAN DIEPEN, MICHIEL T., MARELLI, ANTHONY, BATALOV, SERGEY, MIRAGLIA, LOREN, ORTH, ANTHONY P., RENAUD, NICOLE A., CHARLTON, STEVEN J., GOSLING, MARTIN, GAITHER, L. ALEX and GROOT-KORMELINK, PAUL J., 2014. PLOS ONE. 9(6),
  • MCKEOWN, STEPHEN C., CHARLTON, STEVEN J., COX, BRIAN, FITCH, HELEN, HOWSON, CHRISTOPHER D., LEBLANC, CATHERINE, MEYER, ARNDT, ROSETHORNE, ELIZABETH M. and STANLEY, EMILY, 2014. BIOORGANIC & MEDICINAL CHEMISTRY LETTERS. 24(10), 2247-2250
  • SYKES, DAVID A., PARRY, CHERYL, REILLY, JOHN, WRIGHT, PENNY, FAIRHURST, ROBIN A. and CHARLTON, STEVEN J., 2014. MOLECULAR PHARMACOLOGY. 85(4), 608-617
  • SYKES, DAVID A., RIDDY, DARREN M., STAMP, CRAIG, BRADLEY, MICHELLE E., MCGUINESS, NEIL, SATTIKAR, AFRAH, GUERINI, DANILO, RODRIGUES, INES, GLAENZEL, ALBRECHT, DOWLING, MARK R., MULLERSHAUSEN, FLORIAN and CHARLTON, STEVEN J., 2014. BRITISH JOURNAL OF PHARMACOLOGY. 171(21), 4797-4807
  • ARNOLD N, BEATTIE D, BRADLEY M, BREARLEY A, BROWN L, CHARLTON SJ, FAIRHURST RA, FARR D, FOZARD J, FULLERTON J, GOSLING M, HATTO J, JANUS D, JONES D, JORDAN L, LEWIS C, MAAS J, MCCARTHY C, MERCER M, OAKMAN H, PRESS N, PROFIT R, SCHUERCH F, SYKES D, TAYLOR RJ, TRIFILIEFF A and TUFFNELL A, 2014. Bioorganic & medicinal chemistry letters. 24(17), 4341-7
  • PORTER DW, BRADLEY M, BROWN Z, CHARLTON SJ, COX B, HUNT P, JANUS D, LEWIS S, OAKLEY P, O'CONNOR D, REILLY J, SMITH N and PRESS NJ, 2014. Bioorganic & medicinal chemistry letters. 24(15), 3285-90
  • ROSETHORNE, ELIZABETH M, KENT, TOBY C, FAWCETT, LINDSAY, VAN DIEPEN, MICHIEL T, MARELLI, ANTHONY, BATALOV, SERGEY, CHARLTON, STEVEN J, GOSLING, MARTIN, GAITHER, L ALEX, RENAUD, NICOLE A, GROOT-KORMELINK, PAUL J, ORTH, ANTHONY P, BURCHELL, LYNN, MIRAGLIA, LOREN and BILL, ANKE, 2014. Colony number and mutation rate obtained by hydroxyl amine mediated mutagenesis. Figshare. 1,
  • BRADLEY ME, DOMBRECHT B, MANINI J, WILLIS J, VLERICK D, DE TAEYE S, VAN DEN HEEDE K, ROOBROUCK A, GROT E, KENT TC, LAEREMANS T, STEFFENSEN S, VAN HEEKE G, BROWN Z, CHARLTON SJ and CROMIE KD, 2014. Molecular pharmacology. 87(2), 251-62
  • VAUQUELIN G, HALL D and CHARLTON SJ, 2014. British journal of pharmacology. 172(9), 2300-15
  • NIJMEIJER, S., VISCHER, H. F., SIRCI, F., SCHULTES, S., ENGELHARDT, H., DE GRAAF, C., ROSETHORNE, E. M., CHARLTON, S. J. and LEURS, R., 2013. BRITISH JOURNAL OF PHARMACOLOGY. 170(1), 78-88
  • RIAZ, SAJJAD A., CHARLTON, STEVEN J. and TOBIN, ANDREW B., 2013. STUDIES TO VALIDATE A CHEMICAL GENETIC APPROACH TO INVESTIGATE THE M1 MUSCARINIC RECEPTOR JOURNAL OF RECEPTORS AND SIGNAL TRANSDUCTION. 33(3), 201-201
  • MACKENZIE AE, CALTABIANO G, KENT TC, JENKINS L, MCCALLUM JE, HUDSON BD, NICKLIN SA, FAWCETT L, MARKWICK R, CHARLTON SJ and MILLIGAN G, 2013. Molecular pharmacology. 85(1), 91-104
  • RIDDY, D. M., STAMP, C., SYKES, D. A., CHARLTON, S. J. and DOWLING, M. R., 2012. BRITISH JOURNAL OF PHARMACOLOGY. 167(4), 868-880
  • NIJMEIJER, SASKIA, VISCHER, HENRY F., ROSETHORNE, ELIZABETH M., CHARLTON, STEVEN J. and LEURS, ROB, 2012. MOLECULAR PHARMACOLOGY. 82(6), 1174-1182
  • FIEZ-VANDAL, CEDRIC, LEDER, LUKAS, FREULER, FELIX, SYKES, DAVID, CHARLTON, STEVEN J., SIEHLER, SANDRA, SCHOPFER, ULRICH and DUCKELY, MYRIAM, 2012. BIOPHYSICAL CHEMISTRY. 165, 56-61
  • SYKES, DAVID A. and CHARLTON, STEVEN J., 2012. BRITISH JOURNAL OF PHARMACOLOGY. 165(8), 2672-2683
  • NIJMEIJER, S., ROSETHORNE, E. M., VISCHER, H. F., CHARLTON, S. J. and LEURS, R., 2012. LIGAND-DIRECTED H4R SIGNALLING: A STEP FORWARD TO OPTIMIZED H4R DRUGS? INFLAMMATION RESEARCH. 61, S51-S51
  • CHARLTON, STEVEN J., 2009. BRITISH JOURNAL OF PHARMACOLOGY. 158(1), 165-168

School of Life Sciences

糖心原创
Medical School
Queen's Medical Centre
Nottingham NG7 2UH

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