About
My research focus is host-pathogen interactions in the lungs of patients with chronic respiratory disease, particularly asthma and COPD. To study these interactions, I have led the development of relevant ex vivo models of infection using samples and tissue from the blood and lungs of relevant patient populations. Using lung explant models of influenza infection that I created, we observed that COPD macrophages were unable to restrain the inflammation caused by viral infection rather than the tissue being more susceptible to viral infection as was previously thought. Furthermore, we demonstrated that cigarette smoke aberrantly primes tissue-resident NK cell responses to influenza infection, contributing to the excess inflammation associated with viral exacerbations of COPD. Prevention of infection is key in preventing exacerbations and vaccination one of our most powerful tools for infection prevention. We further used this ex vivo infection model to identify possible new influenza vaccine targets using immunoproteomics. In addition, we demonstrated the antiviral effectiveness of the cytokine, IFNβ, and the dynamics of these responses in macrophages and epithelial cells derived from the airways of COPD patients. At the same time, we observed that influenza-infected macrophages were defective in their ability to phagocytose the bacteria, non-typeable Haemophilus influenzae (NTHi)
As a result of my experience in processing lung samples I was appointed the Laboratory Lead on the AERIS study. This was a complex study to deliver but it is already providing insights into the aetiology of COPD exacerbations, specifically that NTHi was chronically carried in the airways of COPD patients with marked seasonality in its appearance and association with exacerbation frequency. In this study we also observed a marked association between chronic NTHi carriage and viral infection. A possible confounding problem in COPD is the effect of inhaled corticosteroid (ICS) on lung immunity. We demonstrated that ICS use was an independent predictor of community acquired pneumonia in COPD patients. However, there may be multiple mechanisms at work in this susceptibility to bacterial infection, as when we specifically investigated lung samples from COPD patients that were colonised by NTHi, we identified a specific deficiency in IgG1 levels in colonised patients vs non-colonised COPD patients. We also demonstrated a decrease in the numbers of mucosal-associated invariant T cells (MAIT) in the ICS-treated COPD airway. We demonstrated that these MAIT cells have cytotoxic activity against NTHi-infected cells, suggesting that the depletion of MAIT cells can directly impact on NTHi-exacerbations and steroid- associated pneumonias in the COPD airway. In subsequent work using monocyte-derived macrophage (MDM) models that I created, we observed that NTHi was able to persist intracellularly within macrophages by altering its gene expression profile and impacting the host immune response to NTHi. In collaboration with the WATCH study, we went on to show similar host gene expression profiles in NTHi-infected lung macrophages from patients with severe asthma and that this NTHi-induced gene expression programme was driving neutrophilic inflammation, which is resistant to steroid therapy, in severe asthma.
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Teaching
I contribute to teaching and assessment at all levels within the Faculty of Medicine from undergraduate medical students to postgraduate research students, in addition to being a Personal Academic Tutor. At undergraduate level, I teach Pharmacology across the medical programmes. I am the Co-Lead on the Allergic Airways Disease module on the MSc Allergy course. This module has continually improved over the past 8 years, ensuring it remains student centred and relevant to clinical practice. To date I have supervised 14 PhD students to successful completion and am currently main or co-supervisor for a further 4 students. As a result of this supervisory experience, I was appointed the Academic Career Development Lead (ACDL) for the NIHR Southampton Biomedical Research Centre (BRC) in 2019 and am responsible for mentoring and providing for the training needs of scientists, clinicians and allied-health professionals (AHPs) within the BRC.
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Biography
Karl Staples is Professor of Respiratory Immunology & Pharmacology at the University of Southampton Faculty of Medicine, Deputy Head of Clinical & Experimental Sciences for Knowledege Exchange & Enterprise and NIHR Southampton BRC Academic Career Development Lead (ACDL). His research focuses on host-pathogen interactions in chronic inflammatory airways diseases, such as asthma and Chronic Obstructive Pulmonary Disease (COPD), and the contribution of these interactions to exacerbations of these respiratory conditions. To study these interactions he has developed novel ex vivo models of bacterial and viral infection using human lung cells and tissue from relevant patient populations. Using these models he has demonstrated defective control of T cells by lung macrophages in COPD as well as aberrant cigarette-smoke induced priming of NK cells in COPD, both of which may explain how viral infections cause COPD exacerbations. He was Laboratory Lead of the AERIS study which highlighted that NTHi was chronically carried in the airways of COPD patients with marked seasonality in its appearance and association with exacerbation frequency. His subsequent work using his novel models demonstrated that NTHi colonisation was not only associated with increased inflammation in the COPD airway, but that this inflammatory phenotype could be driven by intracellular colonisation of airway macrophages by this bacteria. Furthermore, he led research demonstrating that MAIT cells could control NTHi infection and that corticosteroids could impair this control, indicating how steroid treatment may predispose to pneumonia in NTHi-colonised COPD patients. He is passionate about supporting the next generation of respiratory researchers, having to date supervised 14 PhD students to successful completion and being responsible for mentoring and providing for the training needs of scientists, clinicians and allied-health professionals in his ACDL role.
Prizes
- Fellow of the Higher Education Academy (2008)
- HC Roscoe Award (2013)
- Fellowship of the Royal Society of Biology (2023)
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