个人简介
Dr Susan Wilson is an associate professor and Head of the Histochemistry Research Unit within Medicine at the University of Southampton. Her research focuses on the pathobiology of the allergic inflammatory response and airways remodelling in the lungs in severe asthma and chronic obstructive airways disease (COPD). Teaching responsibilities include coordinating BM5 projects and technical teaching across the Faculty and University.
Susan Wilson initially trained as a Biomedical Scientist in histopathology within the National Health Service. After gaining her Fellowship of the Institute of Biomedical Sciences in Cellular Pathology, she took a position at the University of Southampton. Susan was a founding member of Professor Holgate’s asthma bronchoscopy research programme and provided histopathology support. This work has been key to developing and furthering our understanding of the pathobiology of asthma. During this time she studied for a PhD in Mucosal Inflammation. Susan has over 30 years' experience in histopathology and now heads the Histochemistry Research Unit (HRU) within the Faculty of Medicine and has her own program of research.
The HRU (http://www.som.soton.ac.uk/research/sites/hru/) is a core facility and offers a full histopathology support service for work being undertaken Faculty of Medicine and wider University. The Unit is internationally recognised for its histopathology expertise, having numerous external collaborative links both with academic and commercial organisations across Europe and the USA. It is particularly known internationally for the use of glycol methacrylate (GMA) resin embedding of mucosal biopsies taken from the lung, nose, gut, conjunctiva and skin for immunohistochemistry procedures. A range of image analysis techniques are can then be applied to the stained sections. This GMA technique is utilised for many research projects investigating the mechanisms of mucosal inflammation, particularly asthma, rhinitis and chronic obstructive pulmonary disease (COPD). The HRU also undertakes immunohistochemical analysis for clinical trails, investigating the effects of existing and novel therapeutics on mucosal inflammation.
研究领域
Dr Susan Wilson’s research focuses on the pathobiology of the allergic inflammatory response and airways remodelling in the lungs in severe asthma and chronic obstructive airways disease (COPD). This includes the following current research projects:
The Immunopathology of severe asthma
Severe asthma has a heterogeneous clinical phenotype and pathology. Patients experience frequent exacerbations and/or progressive airways obstruction despite high levels of therapy. Therefore there is a need to develop new treatments that are effective for severe asthma. This is hampered due to the lack of understanding of pathology and molecular disease mechanisms in this patient group. The U-BIOPRED (Unbiased Biomarkers for the Predictions of Respiratory Disease Outcomes) consortium is a pan-European IMI funded study that aims to sub-phenotype severe asthma using an innovative systems medicine approach, including ‘omics’ technologies. This has included clinical and pathological characterisation.
The effects of pollutants on bronchial inflammation in asthma, rhinitis and COPD
Epidemiological evidence demonstrates that exposure to traffic derived pollutants especially diesel exhaust lead to a worsening of asthma symptoms. Collaborative studies with the University of Umeå in Sweden have used controlled human exposure studies to diesel exhaust with the collection of bronchial mucosal samples to investigate the mechanisms responsible for the clinical symptoms. In healthy subjects exposure to diesel induces an increase in cytokine and adhesion molecule expression accompanied by an inflammatory cell influx. This is not observed in subjects with asthma or rhinitis. This differential response to diesel is being investigated further. [Salvi S 2000; Pourazar J 2004, 2005 & 2008; Behndig 2006 & 2011].
Relationship between squamous metaplasia, smoking history and COPD
Normally, the bronchial epithelium is pseudostratified and there is a balance between the rate of cell proliferation, differentiation and cell loss to maintain the epithelial structure and phenotype. However, several factors, including toxic injury induced by cigarette smoke, can disturb this balance and induce squamous metaplasia which is a pre-malignant lesion that can progress to carcinoma in situ and finally to invasive carcinoma. Whilst squamous metaplasia is a well-established feature in the bronchial epithelium of smokers, no studies to date have attempted to quantify it precisely and to relate it to smoking history or COPD status. Identification of squamous metaplasia in bronchial biopsies and its quantification in particular are difficult on the basis of morphology alone. Proper orientation of the biopsies is not always possible, such that areas of epithelium cut perpendicularly are difficult to distinguish from areas of squamous metaplasia, particularly when the cells have an intermediate squamous phenotype. We have, therefore, developed a panel of antibodies for the identification of squamous metaplasia in bronchial biopsies [Merrifield 2010]. Ongoing work is employing this panel to quantify the extent of squamous metaplasia in subjects with and without COPD and to relate it to smoking history.
The role of the eosinophil in the airway remodelling response
It is recognised that asthma, especially severe and fatal, may consists of two eosinophilic phenotypes. Some subjects have a high airway eosinophilia and some a low airway eosinophilia. The presence of eosinophils is regarded as an indicator of corticosteroid responsiveness and risk of exacerbation. How airway eosinophilia is related to remodelling, another key feature of asthma, is poorly understood and is subject of ongoing investigations.
The effects of the anti-IgE antibody, omalizumab
on mechanisms that regulate airway inflammation and to find evidence of effects on airway remodelling in mild to moderate asthmatics We have shown that Omalizumab is able to down-regulate the TH2 allergic inflammatory response in mild asthma. Recent studies have investigated the effects of anti-IgE therapy on the remodelling response, which is also a key feature of asthma [Djukanovic R 2004].
The effects of inhaled corticosteroid and long-acting β2-agonist combination therapy
on airways remodelling We have demonstrated that the addition of a long-acting beta 2 agonist to inhaled low-dose corticosteroid is as effective an anti-inflammatory as higher dose corticosteroid. We are currently investigating the effects of combination therapy on the remodelling features of asthma [Wallin 2003, Jarjour 2006]. This follows on from previous work comparing the anti-inflammatory effects of single therapy with corticosteroids and long-acting beta 2 agonists [Wallin 1999 & 2002; Wilson 2001].
近期论文
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Severe asthma exists despite suppressed tissue inflammation: findings of the U-BIOPRED study - Wilson, Susan J., Ward, Jonathan A., Sousa, Ana , Corfield, Julie, Bansal, Aruna, Meulder, Bertrand, Lefaudeux, Diane, Auffray, Charles, Loza, Matthew, Baribaud, Frederic, Fitch , Neil, Sterk, Peter, Chung, Kian, Gibeon, David, Sun, Kai, Yi-ke, Guo, Adcock, Ian, Djukanovic, Ratko, Dahlen, Barbro, Chanez, Pascal, Shaw, Dominick, Krug, Norbert, Hohlfeld, Jens, Sandtrom, Thomas and Howarth, Peter H. Published:2016Publication:European Respiratory JournalVolume:48, (5)Page Range:1307-1319doi:10.1183/13993003.01129-2016PMID:27799384
A transcriptome-driven analysis of epithelial brushings and bronchial biopsies to define asthma phenotypes in U-BIOPRED - Kuo, Chih-Hsi, Pavlidis, Stelios, Loza, Matthew, Baribaud, Fred, Rowe, Anthony, Pandis, Ioannis, Hoda, Uruj, Rossios, Christos, Sousa, Ana, Wilson, Susan J., Howarth, Peter, Dahlen, Barbro, Dahlen, Sven-Erik, Chanez, Pascal, Shaw, Dominick, Krug, Norbert, Sandstorm, Thomas, Meulder, Bertrand, Lefaudeux, Diane, Fowler, Stephen, Flemming, Louise, Corfield, Julie, Auffray, Charles, Sterk, Peter, Djukanovic, Ratko, Guo, Yike, Adcock, Ian and Chung, Kian Published:2016Publication:American Journal of Respiratory and Critical Care MedicinePage Range:1-57doi:10.1164/rccm.2452OCPMID:27580351
Squamous metaplasia is increased in the bronchial epithelium of smokers with chronic obstructive pulmonary disease - Rigden, Helen M., Alias, Ahmad, Havelock, Tom, O'Donnell, Rory, Djukanovic, Ratko, Davies, Donna E. and Wilson, Susan J. Published:2016Publication:PLoS ONEVolume:11, (5)Page Range:1-11doi:10.1371/journal.pone.0156009PMID:27228128
Morphometric analysis of inflammation in bronchial biopsies following exposure to inhaled diesel exhaust and allergen challenge in atopic subjects - Hosseini, Ali, Hirota, Jeremy A., Hackett, Tillie Louise, McNagny, Kelly M., Wilson, Susan J. and Carlsten, Chris Published:2016Publication:Particle and Fibre ToxicologyVolume:13, (2)Page Range:1-14doi:10.1186/s12989-016-0114-zPMID:26758251
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