个人简介
Andrew Walls has long-standing research interests in the roles of mast cells and basophils in disease. Pioneering studies by his group helped to establish the concept that the proteases of mast cells are key mediators of inflammatory disease and promising targets for therapeutic intervention. The secreted proteases can be effective in cleaving various extracellular proteins, and can induce profound alterations in cell behaviour.
Mast cell proteases and other proteinaceous constituents of mast cells and basophils are proving valuable as cell-specific markers, and tools developed by the group are now widely employed in research and diagnosis. The application of sensitive assays for unique products of mast cells and basophils are advancing understanding of the functions of these cells in allergic and inflammatory conditions of the respiratory and gastrointestinal tracts, joints and at other sites. Of more immediate benefit they are aiding diagnosis of allergic reactions and mastocytosis, conditions for which there has long been a need for laboratory tests.
A range of approaches are being applied including those of immunology, pharmacology, pathology, molecular biology and genetics, and a network of collaborative links has been established with scientists and clinicians locally and across the world. The studies have been reported in over 100 peer reviewed publications in addition to book chapters, reviews and in numerous presentations at national and international meetings. The research has informed approaches currently being developed for new therapies and diagnostic tests.
Andrew Walls has been the principal investigator on grants worth over £5 million. Awards have been received from research councils (Medical Research Council; Biotechnology and Biological Sciences Research Council; Natural Environment Research Council), as well as from other public bodies in the UK and elsewhere (including National Institute for Health Research, Food Standards Agency and the Qatar National Research Fund). Medical research charities that have supported the research include Asthma UK, Wellcome Trust, Arthritis Research UK, Sir Jules Thorne Charitable Trust, Lullaby Trust, Action Research, Thrasher Research Fund, and the Wessex Medical Trust.
There has been a sustained track record of setting up contracts with the pharmaceutical, biotechnology and laboratory supply industries. International patents have been awarded, more than 20 license agreements concluded, and consultancy arrangements set up with biotechnology and pharmaceutical companies in Europe, USA and Japan. He has served also as an expert witness in patent hearings and litigation in European and North American jurisdictions
Andrew Walls was appointed Reader in Immunopharmacology in 2001. Following graduation from the University of Aberdeen, he worked briefly in the Allergens Division of the National Institute for Biological Standards and Control, London, before completing his PhD in the Department of Allergy and Clinical Immunology at the Cardiothoracic Institute, London. He held a research fellowship at the University of York and became interested in mast cells before moving to the University of Southampton to pursue these interests.
研究领域
Proteases, the most abundant products of mast cells, have provided a focus, and studies with mast cell tryptase, chymase, carboxypeptidase and dipeptidyl peptidase I (DPPI) are receiving particular attention. These proteases are emerging as valuable biomarkers for mast cells (Fig 1) and mast cell subsets, as well as key mediators and targets for therapeutic intervention in conditions involving inflammation and tissue remodelling (Fig 2).
Immunopharmacological approaches we have adopted for the study of the proteases involve their transfer (as well as of selective inhibitors) to cell preparations, tissues or living organisms/human subjects, as well as investigating the potential for cleavage of defined substrates. Recognition that mast cell proteases can induce profound alterations in cell behaviour has led us to investigate potential interactions with protease activated receptors (PAR), and particularly with PAR-2.
The proteinaceous constituents of human basophils have been little studied, but our production of basophil-specific monoclonal antibodies has allowed us to detect a unique granule associated component which we have termed 'basogranulin' (Fig 3). Understanding its molecular properties remains a key challenge, but meantime its measurement in biological fluids is allowing for the first time assessment of the extent of basophil activation in clinical disease.
Tools developed by the group are being applied to study the contributions of mast cells and basophils and their subpopulations in allergic conditions such as asthma, rhinitis and anaphylaxis, as well as in other diseases in which mast cells can play a crucial roles including arthritis, neurological conditions, carcinoma and mastocytosis. Measurement of levels of unique mast cell and basophil products in biological fluids is allowing variants of some of these conditions to be defined. Moreover they are indicating that anaphylactic processes may underlie some fatal conditions for which underlying mechanisms have not been clear, eg some cases of sudden unexpected death in infancy and reactions provoked by drug abuse. The studies are providing new diagnostic methods and offering insights into better management and treatment of conditions involving mast cell or basophil activation.
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Innate and adaptive T cells in asthmatic patients: relationship to severity and disease mechanisms - Hinks, Timothy S.C., Zhou, Xiaoying, Staples, Karl J., Dimitrov, Borislav D., Manta, Alexander, Petrossian, Tanya, Lum, Pek Y., Smith, Caroline G., Ward, Jon A., Howarth, Peter H., Walls, Andrew F., Gadola, Stephan D. and Djukanović, Ratko Published:2015Publication:Journal of Allergy and Clinical ImmunologyVolume:136, (2)Page Range:323-333doi:10.1016/j.jaci.2015.01.014PMID:25746968
Multidimensional endotypes of asthma: topological data analysis of cross-sectional clinical, pathological and immunological data - Hinks, Timothy, Zhou, Xiaoying, Staples, Karl, Dimitrov, Borislav, Manta, Alexander, Petrossian, Tanya, Lum, Pek, Smith, Caroline, Ward, Jon, Howarth, Peter, Walls, Andrew, Gadola, Stephan and Djukanovic, Ratko Published:2015Publication:The LancetVolume:385Page Range:S42doi:10.1016/S0140-6736(15)60357-9PMID:26312864
Multidimensional endotypes of asthma: topological data analysis of cross-sectional clinical, pathological, and immunological data - Hinks, Timothy, Zhou, Xiaoying, Staples, Karl, Dimitrov, Borislav, Manta, Alexander, Petrossian, Tanya, Lum, Pek, Smith, Caroline, Ward, Jon, Howarth, Peter, Walls, Andrew, Gadola, Stephan D. and Djukanović, Ratko Published:2015Publication:The LancetVolume:385Page Range:S42doi:10.1016/S0140-6736(15)60357-9PMID:26312864
Alpha-tryptase gene variation is associated with levels of circulating IgE and lung function in asthma - Abdelmotelb, A.M., Rose-Zerilli, M.J., Barton, S.J., Holgate, S.T., Walls, A.F. and Holloway, J.W. Published:2014Publication:Clinical & Experimental AllergyVolume:44, (6)Page Range:822-830doi:10.1111/cea.12259PMID:24372627
Multidimensional phenotypes of asthma - Hinks, T.S.C., Zhou, X.Y., Lum, P., Staples, K.J., Dimitrov, B., Smith, C., Ward, J., Howarth, Peter H., Walls, A.F., Gadola, S.D. and Djukanovic, Ratko Published:2013Publication:ThoraxVolume:, (68)Page Range:A14-A15doi:10.1136/thoraxjnl-2013-204457.30
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