Postle, Tony - University of Southampton

个人简介

Professor Tony Postle is Professor in Developmental Biochemistry within Medicine at the University of Southampton. Tony Postle has a PhD in the regulation of lipid metabolism from the University of Southampton. His major research interest is the interactions of diet, development and disease in the regulation of phospholipid compositions of cell membranes and, in turn, how altered membrane structures contribute to disease processes. In particular, the focus of his research are the mechanisms whereby lipid signalling and oxidation of lipids contribute to inflammatory processes in a wide range of pathological states, including respiratory, cardiovascular, cancer and neurological diseases. He has established one of the major lipidomics research groups in the UK, supported by a state of the art mass spectrometry facility.

研究领域

Phospholipids are vital to maintenance of the integrity of cell membranes, and phospholipase-mediated hydrolysis of specific phospholipids regulates a host of cellular processes including cell division, differentiation and inflammation. All cell types in the body have a closely regulated and characteristic composition of membrane phospholipid, which is generally lost for cells maintained in tissue culture. ESI-MS analysis now permits the detailed analysis not only of the molecular compositions of membrane and signalling lipids but also of their rates of synthesis and turnover using stable isotopes. As stable isotopes are not radioactive, this approach is now also being applied to clinical studies of lipid metabolism. Specific areas of current research are given below. The molecular specificity of lung surfactant phospholipid Lung surfactant is the natural phospholipid-rich detergent produced by the lungs that is essential to prevent lung collapse during breathing. Insufficiency or inactivation of surfactant is a major cause of respiratory failure in preterm infants and in patients in Intensive Care, and contributes to the pathology of a wide range of other lung diseases including asthma, cystic fibrosis and chronic obstructive pulmonary disease. This research is both analysing surfactant components in lung washing samples as biomarkers of disease progression and investigating the mechanisms regulating the synthesis, secretion and turnover of surfactant phospholipid. The goal of this work is the design of novel surfactant formulations that can be given to treat diseases of the mature lung. This experimental approach currently being applied to characterize surfactant phospholipid synthesis and secretion in preterm infants at risk of developing neonatal chronic lung disease and in older children and adults ventilated in Paediatric and Adult Intensive Care for acute respiratory distress syndrome/acute lung injury. This research is funded by the National Institute for Health Research Respiratory Biomedical Research Unit. Lipid oxidation Free radical-mediated oxidation of unsaturated fatty acids in phospholipids contributes to the initiation and progression of many diseases, possibly best established for atherosclerosis. Such oxidation initially generates hydroperoxides followed by further chemical decomposition to truncated, biologically active, shorter chain molecules such as aldehydes, carboxylates and hydroxyls. The Postle group has established mass spectrometry methods to characterise and quantify this complex mixture of oxidised phospholipids bass on accurate mass analysis, based on the observation that individual atoms have masses that are not exact integers. This is especially relevant for hydrogen, with a mass of 1.008, and phospholipid species with the same nominal mass but comprised of different numbers of hydrogen, oxygen and carbon atoms will have mass differences of 0.04-0.12 Da. The Wellcome Trust has funded a high resolution Fourier Transformed Ion Cyclotron Resonance Mass Spectrometer (FT-ICR MS) to explore the extent to which such oxidised lipids act as initiators of cell dysfunction or can be used as surrogate biomarkers of disease progression in a wide range of conditions. These include respiratory failure in preterm infants (with Professor Howard Clark), children (Dr John Pappachan) and adults (Professor Mike Grocott), in asthma, chronic obstructive pulmonary disease (Professor Ratko Djukanovic), in endothelial cell dysfunction (Professor Geraldine Clough), oxidation of pharmaceuticals and biodiesel (Dr John Langley), in modelling neurodegeneration in vitro (Dr Ashley Pringle), in prion disease and neurodegeneration (Professor Hugh Perry) and in unstable atherosclerotic plaque (Professor Alberto Smith: NIHR BRC, St Thomas’s Hospital).

近期论文

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Cholesteryl esters stabilize human CD1c conformations for recognition by self-reactive T cells - Mansour, Salah, Tocheva, Anna S., Cave-Ayland, Christopher, Machelett, Moritz M., Sander, Barbara, Lissin, Nikolai M., Molloy, Peter E., Baird, Mark S., Stübs, Gunthard, Schröder, Nicolas W.J., Schumann, Ralf R., Rademann, Jörg, Postle, Anthony D., Jakobsen, Bent K., Marshall, Ben G., Gosain, Rajendra, Elkington, Paul T, Elliott, Timothy, Skylaris, Chris-Kriton, Essex, Jonathan W., Tews, Ivo and Gadola, Stephan D. Published:2016Publication:Proceedings of the National Academy of SciencesVolume:113, (9)Page Range:E1266-E1275doi:10.1073/pnas.1519246113PMID:26884207 Antioxidant role for lipid droplets in a stem cell niche of Drosophila - Bailey, Andrew P., Koster, Grielof, Guillermier, Christelle, Hirst, Elizabeth M.A., MacRae, James I., Lechene, Claude P., Postle, Anthony D. and Gould, Alex P. Published:2015Publication:CellVolume:163, (2)Page Range:340-353doi:10.1016/j.cell.2015.09.020PMID:26451484 Ready-to-use therapeutic food with elevated n-3 polyunsaturated fatty acid content, with or without fish oil, to treat severe acute malnutrition: a randomized controlled trial - Jones, K.D., Ali, R., Khasira, M.A., Odera, D., West, A.L., Koster, G., Akomo, P., Talbert, A.W., Goss, V.M., Thitiri, J., Ndoro, S., Knight, M.A., Omollo, K., Ndungu, A., Mulongo, M.M., Bahwere, P., Fegan , G., Warner, J.O., Postle, A.D., Collins, S., Calder, P.C. and Berkley, J.A.Ngari, M. (ed.) Published:2015Publication:BMC MedicineVolume:13Page Range:93-93doi:10.1186/s12916-015-0315-6PMID:25902844 Altered molecular specificity of surfactant phosphatidycholine synthesis in patients with acute respiratory distress syndrome - Dushianthan, Ahilanandan, Goss, Victoria, Cusack, Rebecca, Grocott, Michael P.W. and Postle, Anthony D. Published:2014Publication:Respiratory ResearchVolume:15, (1)Page Range:1-11doi:10.1186/s12931-014-0128-8PMID:25378080 Effect of darapladib treatment on endarterectomy carotid plaque lipoprotein-associated phospholipase A2 activity: a randomized, controlled trial - Johnson, Joel L., Shi, Yi, Snipes, Rose, Janmohamed, Salim, Rolfe, Timothy E., Davis, Bill, Postle, Anthony and Macphee, Colin H. Published:2014Publication:PLoS ONEVolume:9, (2)Page Range:1-9doi:10.1371/journal.pone.0089034PMID:24586490