Madsen, Jens - University of Southampton

个人简介

Dr Madsen completed his undergraduate studies at Odense University, Denmark with a Bachelor Degree in Molecular Biology followed by a Master of Science degree in Biomedicine. His PhD degree in Immunology was gained from University of Southern Denmark in 2002 followed by a postdoctoral position at the same institution. His second postdoctoral position was at University of California San Francisco from 2004 until 2007 investigating the importance of innate immunity against influenza A virus infections. Since September 2007, Dr. Madsen has been a Lecturer in Child Health at the Faculty of Medicine, University of Southampton. Dr Madsen’s research focus on airways and the importance of innate immunity for the maintenance of a normal healthy lung and during infection, inflammation and repair processes.

研究领域

Dr Madsen’s research area is mainly focused on the role of a group of proteins called ‘collectins’ which are a part of the innate immune system in health and disease. These molecules have important roles in the innate immune system but additional roles in the adaptive immune system and other areas are emerging. Collectins are oligomerised C-type lectins with a collagenous domain, hence the name col-lectin. The word lectin comes from the Latin ‘legere’ which means ‘to select’ and lectins are sugar-binding proteins which are highly specific for certain carbohydrates. Collectins bind to soluble carbohydrates or to a carbohydrate moiety which could be part of a glycoprotein or glycolipid, which is located on the surface of viruses, bacteria and other glycosylated micro particles like pollen. Collectins facilitate clearance of these particles from the body using clearance mechanisms such as the muco-cilial staircase in the airways and by phagocytosis by immune cells such as dendritic cells, macrophages and neutrophils. Dr Madsen has a particular interest in the collectins Surfactant Protein A (SP-A) and Surfactant Protein D (SP-D). These proteins were originally identified in surfactant, the lining fluid of the lungs responsible for lowering surface tension in the lungs of mammals. This effect is essential for the process of breathing and without surfactant the air sacs of the lungs would collapse during exhaling. SP-D is not only present in the lung but expressed and localised in epithelial cells throughout the body on all mucosal surfaces and secreted to and found in several body fluids such as saliva and tears. At these sites SP-D facilitate clearance of potential pathogenic microorganisms like viruses and bacteria. Genetic studies have recently shown that small natural differences or ‘short nucleotide polymorphisms’ (SNP’s) are found in the genes encoding for SP-A and SP-D, respectively. Dr Madsen is focusing on a SNP named Met/Thr(11) found in position 11 of the human SP-D molecule, an important region for the oligomerisation of the mature molecule. Individuals homozygotic for Met(11) have higher oligomerised forms of SP-D in comparison to individuals homozygotic for Thr(11) SP-D. Clinical studies have shown that people having Met(11) are more susceptible to Tuberculosis while infants with Thr(11) are more susceptible to severe infections with Respiratory Syncytial Virus. Dr Madsen is investigating, in collaboration with Professor Howard Clark, Chair of Child Health, the roles of SP-A and SP-D in health and disease and in particular the Met/Thr(11) differences in respiratory viral infections such as Respiratory Syncytial virus or Influenza A virus. Our collaborative research also focuses on whether a recombinant fragment of human SP-D can be used as a potential therapeutic against respiratory diseases and in addition treatment of inflammatory conditions such as asthma, cystic fibrosis, neonatal chronic lung disease and adult emphysema.

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