Holden, Neil - University of Lincoln - School of Life Sciences

个人简介

Senior Lecturer in Life Sciences in the College of Science My major research interests revolve around the interaction between anti-inflammatory and pro-inflammatory pathways in inflammatory airway diseases predominantly Asthma and chronic obstructive pulmonary disease (COPD). Corticosteroids (aka glucocorticoids) are the mainstay therapy of the inflammatory lung diseases asthma and COPD. In more severe cases of these diseases they are often taken in combination with “reliever” therapies, such as long acting Beta 2 adrenergic receptor agonists (LABA’s), as these combinations have been shown to be more beneficial than corticosteroids alone. However it is not entirely clear the anti-inflammatory molecular mechanisms these drugs activate within the various lung cells. I have previously developed a strong interest in proteins who have potential anti-inflammatory activities and whose expression is driven by corticosteroids and/or LABAs. My current research projects are focused on the interaction of these anti-inflammatory proteins with respiratory viruses, which are the leading causes of exacerbations and therefore morbidity and mortality in asthma and COPD. Department Responsibilities Lecturers in various Modules on Virology, Immunology, Respiratory Pharmacology, and Airway Diseases Module leader for Medical and Veterinary Microbiology Module Leader for Fundamentals of Pharmacology and Toxicology Subject Specialism Airway Inflammatory Diseases, Asthma & COPD, Virology and Immunology Qualifications PhD in Molecular Physiology — The University of Warwick, 2006 BSc in Virology with Intercalated Year — The University of Warwick, 2001 Awards Eric Reid Fund for Methodology — Biochemical Society, 2015 Izaac Walton Killam Postdoctoral Fellowship — Killam Trusts, 2008

研究领域

Asthma beta 2 adrenoceptor agonists COPD Corticosteroids Inflammation Respiratory Syncytial Virus Viruses

近期论文

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Holden, Neil S. and George, Tresa and Rider, Christopher F. and Chandrasekhar, Ambika and Shah, Suharsh and Kaur, Manminder and Johnson, Malcolm and Siderovski, David P. and Leigh, Richard and Giembycz, Mark A. and Newton, Robert (2014) Induction of regulator of G-protein signaling 2 expression by long-acting β2-adrenoceptor agonists and glucocorticoids in human airway epithelial cells.. Journal of Pharmacology and Experimental Therapeutics, 348 (1). pp. 12-24. ISSN: 0022-3565 Kelly, M. M. and King, E. M. and Rider, C. F. and Gwozd, C. and Holden, Neil S. and Eddleston, J. and Zuraw, B. and Leigh, R. and O'Byrne, P. M. and Newton, R. (2012) Corticosteroid-induced gene expression in allergen-challenged asthmatic subjects taking inhaled budesonide.. British Journal of Pharmacology, 165 (6). pp. 1737-1747. ISSN: 0007-1188 Holden, Neil S. and Bell, Matthew J. and Rider, Christopher F. and King, Elizabeth M. and Gaunt, David D. and Leigh, Richard and Johnson, Malcolm and Siderovski, David P. and Heximer, Scott P. and Giembycz, Mark A. and Newton, Robert (2011) β2-Adrenoceptor agonist-induced RGS2 expression is a genomic mechanism of bronchoprotection that is enhanced by glucocorticoids.. Proceedings of the National Academy of Sciences of the United States of America, 108 (49). pp. 19713-19718. ISSN: 1091-6490 Rider, Christopher F. and King, Elizabeth M. and Holden, Neil S. and Giembycz, Mark A. and Newton, Robert (2011) Inflammatory stimuli inhibit glucocorticoid-dependent transactivation in human pulmonary epithelial cells: rescue by long-acting beta2-adrenoceptor agonists. Journal of Pharmacology and Experimental Therapeutics, 338 (3). pp. 860-869. ISSN: 0022-3565 Holden, Neil S. and Tacon, Claire E. (2011) Principles and problems of the electrophoretic mobility shift assay. Journal of Pharmacological and Toxicological Methods, 63 (1). pp. 7-14. ISSN: 1056-8719 Tacon, Claire E. and Wiehler, Shahina and Holden, Neil S. and Newton, Robert and Proud, David and Leigh, Richard (2010) Human rhinovirus infection up-regulates MMP-9 production in airway epithelial cells via NF-{kappa}B. American Journal of Respiratory Cell and Molecular Biology, 43 (2). pp. 201-209. ISSN: 1044-1549 Holden, Neil S. and Rider, C. F. and Bell, M. J. and Velayudhan, J. and King, E. M. and Kaur, M. and Salmon, M. and Giembycz, M. A. and Newton, R. (2010) Enhancement of inflammatory mediator release by beta(2)-adrenoceptor agonists in airway epithelial cells is reversed by glucocorticoid action.. British journal of pharmacology, 160 (2). pp. 410-420. ISSN: 0007-1188 Newton, Robert and King, Elizabeth M. and Gong, Wei and Rider, Christopher F. and Staples, Karl J. and Holden, Neil S. and Bergmann, Martin W. (2010) Glucocorticoids inhibit IL-1beta-induced GM-CSF expression at multiple levels: roles for the ERK pathway and repression by MKP-1.. The Biochemical Journal, 427 (1). pp. 113-24. ISSN: 0264-6021 King, Elizabeth M. and Holden, Neil S. and Gong, Wei and Rider, Christopher F. and Newton, Robert (2009) Inhibition of NF-kappaB-dependent transcription by MKP-1: transcriptional repression by glucocorticoids occurring via p38 MAPK. The Journal of biological chemistry, 284 (39). pp. 26803-26815. ISSN: 0021-9258 King, Elizabeth M. and Kaur, Manminder and Gong, Wei and Rider, Christopher F. and Holden, Neil S. and Newton, Robert (2009) Regulation of tristetraprolin expression by interleukin-1β and dexamethasone in human pulmonary epithelial cells: Roles for nuclear factor-κB and p38 mitogen-activated protein kinase. The journal of pharmacology and experimental therapeutics, 330 (2). pp. 575-585. ISSN: 0022-3565 Zaheer, Raza S. and Koetzler, Rommy and Holden, Neil S. and Wiehler, Shahina and Proud, David (2009) Selective transcriptional down-regulation of human rhinovirus-induced production of CXCL10 from airway epithelial cells via the MEK1 pathway.. Journal of Immunology, 182 (8). pp. 4854-4864. ISSN: 0022-1767 Koetzler, Rommy and Zaheer, Raza S. and Wiehler, Shahina and Holden, Neil S. and Giembycz, Mark A. and Proud, David (2009) Nitric oxide inhibits human rhinovirus-induced transcriptional activation of CXCL10 in airway epithelial cells. The Journal of Allergy and Clinical Immunology, 123 (1). pp. 201-208.e9. ISSN: 0091-6749 Kaur, Manminder and Holden, Neil S. and Wilson, Sylvia M. and Sukkar, Maria B. and Chung, Kian Fan and Barnes, Peter J. and Newton, Robert and Giembycz, Mark A. (2008) Effect of β2-adrenoceptor agonists and other cAMP-elevating agents on inflammatory gene expression in human ASM cells: a role for protein kinase A. American journal of physiology. Lung cellular and molecular physiology, 295 (3). pp. L505-L514. ISSN: 1040-0605 Holden, Neil S. and Squires, Paul E. and Kaur, Manminder and Bland, Rosemary and Jones, Carol E. and Newton, R. (Robert) (2008) Phorbol ester-stimulated NF-kappa B-dependent transcription : roles for isoforms of novel protein kinase C. Cellular Signalling, 20 (7). pp. 1338-1348. ISSN: 0898-6568 Holden, Neil S. and Gong, W. and King, E. M. and Kaur, M. and Giembycz, M. A. and Newton, R. (2007) Potentiation of NF-κB-dependent transcription and inflammatory mediator release by histamine in human airway epithelial cells. British journal of pharmacology, 152 (6). pp. 891-902. ISSN: 0007-1188 Newton, Robert and Holden, Neil S. (2007) Separating transrepression and transactivation: a distressing divorce for the glucocorticoid receptor?. Molecular pharmacology, 72 (4). pp. 799-809. ISSN: 0026-895X Newton, Robert and Holden, Neil S. and Catley, Matthew C. and Oyelusi, Wale and Leigh, Richard and Proud, David and Barnes, Peter J. (2007) Repression of inflammatory gene expression in human pulmonary epithelial cells by small-molecule IκB kinase inhibitors. The journal of pharmacology and experimental therapeutics, 321 (2). pp. 734-42. ISSN: 0022-3565 Chivers, Joanna E. and Gong, Wei and King, Elizabeth M. and Seybold, Joachim and Mak, Judith C. and Donnelly, Louise E. and Holden, Neil S. and Newton, Robert (2006) Analysis of the dissociated steroid RU24858 does not exclude a role for inducible genes in the anti-inflammatory actions of glucocorticoids.. Molecular pharmacology, 70 (6). pp. 2084-2095. ISSN: 0026-895X Catley, Matthew C. and Chivers, Joanna E. and Holden, Neil S. and Barnes, Peter J. and Newton, Robert (2005) Validation of IKK beta as therapeutic target in airway inflammatory disease by adenoviral-mediated delivery of dominant-negative IKK beta to pulmonary epithelial cells. British journal of pharmacology, 145 (1). pp. 114-22. ISSN: 0007-1188 Catley, Matthew C. and Cambridge, Lisa M. and Nasuhara, Yasuyuki and Ito, Kazuhiro and Chivers, Joanna E and Beaton, Andrew and Holden, Neil S. and Bergmann, Martin W. and Barnes, Peter J. and Newton, Robert (2004) Inhibitors of protein kinase C (PKC) prevent activated transcription: role of events downstream of NF-kappaB DNA binding. Journal of Biological Chemistry, 279 (18). pp. 18457-18466. ISSN: 0021-9258 Holden, Neil S. and Catley, Matthew C. and Cambridge, Lisa M. and Barnes, Peter J. and Newton, Robert (2004) ICAM-1 expression is highly NF-kappaB-dependent in A549 cells. No role for ERK and p38 MAPK. European Journal of Biochemistry / FEBS, 271 (4). pp. 785-791. ISSN: 1742-464X Catley, Matthew C. and Chivers, Joanna E. and Cambridge, Lisa M. and Holden, Neil and Slater, Donna M. and Staples, Karl J. and Bergmann, Martin W. and Loser, Peter and Barnes, Peter J. and Newton, Robert (2003) IL-1beta-dependent activation of NF-kappaB mediates PGE2 release via the expression of cyclooxygenase-2 and microsomal prostaglandin E synthase. FEBS Letters, 547 (1-3). pp. 75-79. ISSN: 0014-5793 Newton, Robert and Holden, Neil (2003) Inhibitors of p38 mitogen-activated protein kinase. BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy, 17 (2). pp. 113-29. ISSN: 1173-8804