Imperial College London

DrAranSinganayagam

Faculty of MedicineNational Heart & Lung Institute

Senior Clinical Research Fellow
 
 
 
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Contact

 

a.singanayagam

 
 
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Location

 

Medical SchoolSt Mary's Campus

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Summary

 

Summary

Aran Singanayagam is an MRC Clinician Scientist, Group Leader at the Centre for Molecular Bacteriology and Infection (CMBI) at Imperial College and Honorary Consultant in Respiratory Medicine at the Royal Brompton and Harefield NHS trust.

Aran qualified from the University of Edinburgh medical school in 2005. He intercalated with a BSc. in Physiology and was awarded First Class Honours. In 2009, he was appointed to the post of NIHR Academic Clinical Fellow in Respiratory Medicine at Imperial College. A Wellcome Trust Clinical Research Training Fellowship enabled him to undertake a PhD. using experimental models to understand how the commonly used inhaled therapy fluticasone propionate can impair immune responses to rhinovirus infection. He identified type I interferon as a central regulator of antibacterial immunity and mucus production during virus-induced exacerbations of COPD. This work led to a first author publication in Nature Communications (accessible here).

Aran then took up an NIHR Academic Clinical Lecturer post to develop a niche studying mechanisms of dysregulated host-defence in chronic lung disease. He built upon his PhD. work by demonstrating that inhaled corticosteroids can perturb the airway microbiota and impair bacterial control through suppression of the anti-microbial peptide cathelicidin, an effect that occurs mechanistically through augmentation of the protease cathepsin D, a negative regulator of cathelicidin. This work has been published in Science Translational Medicine (accessible here).

Subsequently, Aran was awarded a Wellcome Trust ISSF Springboard Fellowship followed by a prestigious MRC Clinician Scientist Fellowship which enabled him to establish his research group studying the role of the respiratory tract microbiota in innate immunity.

Aran has received prestigious early career investigator awards from the British Thoracic Society (BTS), the European Respiratory Society (ERS) and the Worshipful Society of Apothecaries. He was a member of the BTS Science and Research Committee (2015-2018) and the ERS Long Range Planning Committee for Respiratory Infection (2015-2018). He sits on the Editorial Board of the European Respiratory Journal and has published a total of 80 papers to date with a H index of 36.

RESEARCH INTERESTS

Aran's research program focusses on how pulmonary host-defence is dysregulated in the context of inflammatory airway diseases. Major research themes currently include:

Understanding the role played by the respiratory tract microbiota in innate anti-microbial immunityWe are using cutting-edge immunological and molecular microbiological techniques in human and animal disease models to gain functional understanding of roles played by the respiratory tract microbiota. We are focussing on how commensals within the microbiota regulate immune homeostasis in health and how perturbations that occur in chronic lung diseases lead to immune dysregulation and impaired protection against pathogens.

Investigating the role of respiratory tract mucins in mucosal host-defence: With funding from the British Lung Foundation and British Medical Association, we are examining the role of respiratory tract mucins in innate immune responses to viral and bacterial pathogens in asthma and COPD (featured on World COPD Day 2017, see details here).

Mechanisms of susceptibility to SARS-COV-2 in high risk groups: We are combining ex vivo approaches with analyses of in vivo samples from patients to determine what drives altered susceptibility to severe COVID-19 in chronic lung disease with the aim of identifying novel druggable targets.

Selected Publications

Journal Articles

Kamal F, Glanville N, Xia W, et al., 2020, Beclomethasone has lesser suppressive effects on inflammation and anti-bacterial immunity than Fluticasone or Budesonide in experimental infection models., Chest, Vol:158, ISSN:0012-3692, Pages:947-951

Finney LJ, Glanville N, Farne H, et al., Inhaled corticosteroids downregulate the SARS-CoV-2 receptor ACE2 in COPD through suppression of type I interferon

Ritchie AI, Singanayagam A, 2020, Immunosuppression for hyperinflammation in COVID-19: a double-edged sword?, The Lancet, Vol:395, ISSN:0140-6736, Pages:1111-1111

Singanayagam A, Loo S-L, Calderazzo MA, et al., 2019, Antiviral immunity is impaired in COPD patients with frequent exacerbations, American Journal of Physiology - Lung Cellular and Molecular Physiology, Vol:317, ISSN:1040-0605, Pages:L893-L903

Patel DF, Peiro T, Bruno N, et al., 2019, Neutrophils restrain allergic airway inflammation by limiting ILC2 function and monocyte-dendritic cell antigen presentation, Science Immunology, Vol:4, ISSN:2470-9468

Singanayagam A, Snelgrove RJ, 2019, Less burn, more fat: electronic cigarettes and pulmonary lipid homeostasis, Journal of Clinical Investigation, Vol:129, ISSN:0021-9738, Pages:4077-4079

Singanayagam A, Glanville N, Cuthbertson L, et al., 2019, Inhaled corticosteroid suppression of cathelicidin drives dysbiosis and bacterial infection in chronic obstructive pulmonary disease, Science Translational Medicine, Vol:11, ISSN:1946-6234, Pages:1-13

Singanayagam A, Footitt J, Kasdorf BT, et al., MUC5AC drives COPD exacerbation severity through amplification of virus-induced airway inflammation

Singanayagam A, Glanville N, Girkin J, et al., 2018, Corticosteroid suppression of antiviral immunity increases bacterial loads and mucus production in COPD exacerbations, Nature Communications, Vol:9, ISSN:2041-1723

Singanayagam A, Glanville N, Walton RP, et al., 2015, A short-term mouse model that reproduces the immunopathological features of rhinovirus-induced exacerbation of COPD, Clinical Science, Vol:129, ISSN:1470-8736, Pages:245-258

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