Clark, Howard - University of Southampton

个人简介

Prof Howard Clark BA MA MB BChir MA MD (Cantab) MA DPhil (Oxon) MRCP MRCPCH is Professor of Child Health and Head of the Academic Department of Child Health at the University of Southampton and Honorary Consultant in Paediatrics (Neonatal Medicine) at the Southampton University Hospitals Trust. Professor Clark read medicine at Gonville and Caius College, Cambridge and completed a degree in Philosophy before completing clinical training at Cambridge University Clinical School at Addenbrooke’s hospital in Cambridge. After completing general paediatric training at the Royal Hospital for Children in Bristol and Queen Elizabeth Hospital for Children in Hackney, London, he took up a Fellowship in Neonatal-Perinatal Medicine at the Cardiovascular Research Institute and Department of Paediatrics at the University of California, San Francisco (UCSF) in the United States. In addition to training in neonatology he carried out basic research on lung surfactant biochemistry and metabolism in the laboratories of Dr John Clements and Professor Samuel Hawgood for which he was awarded the MD by Cambridge University. On returning to Britain as Eden Fellow in Paediatrics of the Royal College of Physicians of London he carried out basic research on lung surfactant proteins A and D at the MRC Immunochemistry Unit in the Department of Biochemistry, University of Oxford for which he was awarded the DPhil. He was awarded a Beit Memorial Fellowship for Medical Research to continue these studies and was appointed as an MRC Senior Scientist in 2002, completing clinical training in neonatology at the John Radcliffe Hospital. Whilst in Oxford Professor Clark demonstrated that a recombinant fragment of surfactant protein D was an effective anti inflammatory agent in models of allergic and infectious lung disease and demonstrated a key function of surfactant protein D in the clearance of apoptotic cells in the lung showing that this mechanism was protective against the development of pulmonary emphysema. Prof Clark was awarded the 2002 Medical Futures Glaxo SmithKline Award for the best Innovation to Improve Child Health and the Young Investigator Medal of the Royal College of Paediatrics and Child Health. He was awarded a Senior Research Fellowship in Medicine at Mansfield College, Oxford in 2004 and left Oxford to take up his current position as Head of the Department of Child Health at Southampton in 2007.

研究领域

Professor Clark’s research focus is on the structure function relationships of surfactant proteins A and D and their roles in health and disease. With Professor Tony Postle he leads the surfactant biology group in the Department of Child Health and a major impetus of the group’s research is to apply basic biochemical and physiological understanding relating to surfactant composition structure and function to the development of second generation lung surfactant therapies for a wide range of lung diseases including, neonatal respiratory distress syndrome, asthma, cystic fibrosis, lung infection and pulmonary emphysema. Professor Clark has been involved in translational medical research since the very first successful clinical trials of the first artificial surfactant were carried out in the UK for neonatal RDS- including the first dry powder surfactant ALEC developed in Cambridge. He was also involved with the first clinical trials of Exosurf in the US and in the UK. Whilst current surfactant therapy with animal sourced surfactants such as Survanta and Curosurf has been very successful in reducing mortality from neonatal RDS, approximately 40% of infants surviving after birth at less than 28 weeks gestation have chronically inflamed lungs and develop neonatal chronic lung disease. Current surfactants do not contain SP-A and SP-D. We have characterized a recombinant fragment of surfactant protein D which may have beneficial adjunctive effects to reduce inflammation and thus reduce the incidence of these co-morbidities. Our research has also demonstrated however that these surfactant proteins are also involved in inhibiting allergy and generally in the protection of mucosal surfaces from noxious pro-inflammatory stimuli. We are currently attempting to characterize surfactant abnormalities in detail in cohorts of patients with respiratory disease with the aim of identifying subgroups of patients who might benefit from current surfactant therapy or surfactant specifically designed to repair the damage done to the endogenous surfactant system in common lung diseases.

近期论文

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Novel expression of a functional trimeric fragment of human SP-A with efficacy in neutralisation of RSV - Watson, Alastair, Kronqvist, Nina, Spalluto, C. Mirella, Griffiths, Mark, Staples, Karl J., Wilkinson, Tom, Holmskov, Uffe, Sorensen, Grith L., Rising, Anna, Johansson, Jan, Madsen, Jens and Clark, Howard Published:2016Publication:ImmunobiologyPage Range:1-8doi:10.1016/j.imbio.2016.10.015 Effect of irradiation/bone marrow transplantation on alveolar epithelial type II cells is aggravated in surfactant protein D deficient mice - Muhlfeld, C., Madsen, J., Mackay, R.-M., Schneider, J.P., Schipke, J., Lutz, D., Birkelbach, B., Knudsen, L., Botto, M., Ochs, M. and Clark, Howard Published:2016Publication:Histochemistry and Cell BiologyPage Range:1-13doi:10.1007/s00418-016-1479-7PMID:27565967 Nanoparticles in the lung and their protein corona: the few proteins that count - Whitwell, Harry, Mackay, Rose-Marie, Elgy, Christine, Morgan, Cliff, Griffiths, Mark, Clark, Howard, Skipp, Paul and Madsen, Jens Published:2016Publication:NanotoxicologyPage Range:1-24doi:10.1080/17435390.2016.1218080PMID:27465202 Crystal structure of a complex of surfactant protein D (SP-D) and Haemophilus influenzae lipopolysaccharide reveals shielding of core structures in SP-D-resistant strains - Clark, Howard W., Mackay, Rose-Marie, Deadman, Mary E, Hood, Derek W, Madsen, Jens, Moxon, E. Richard, Townsend, J. Paul, Reid, Kenneth B.M., Ahmed, Abdul, Shaw, Amy J., Greenhough, Trevor J. and Shrive, Annette K. Published:2016Publication:Infection and ImmunityVolume:84, (5)Page Range:1585-1592doi:10.1128/IAI.01239-15PMID:26953329