The University of Sheffield
Department of Infection and Immunity

Professor Ian Sabroe MBBS BSc AKC PhD FRCP

Ian Sabroe

Academic Unit of Respiratory Medicine
Department of Infection and Immunity
The Medical School
Beech Hill Road
Sheffield
S10 2RX
UK

Tel: +44 (0)114 271 3243
Email: i.sabroe@sheffield.ac.uk
Secretary:  Jean Lazenby
Tel:  +44 (0)114 271 2237
Email:  j.lazenby@sheffield.ac.uk
Fax:  +44 (0)114 271 3892

Biography

I am a respiratory physician with clinical interests in severe asthma and in pulmonary hypertension, and research interests in mechanisms of airway and vascular inflammation. My group is looking for new ways of understanding and treating human lung disease, particularly where it involves inflammation.

I undertook most of my clinical training in London, with respiratory training particularly at the Hammersmith Hospital, the Royal Brompton Hospital, and Imperial College London, in Prof Tim Williams's lab, coupled with a brief research elective with Prof Craig Gerard (Harvard).

I moved to Sheffield in 2000 on an MRC Clinician Scientist Fellowship, and subsequently an MRC Senior Clinical Fellowship, to study how TLR-driven inflammation contributes to airways disease. I established the severe asthma clinical service, and now actively participate in the delivery of care to patients with pulmonary arterial hypertension.

Research Interests

My group has numerous interests within respiratory medicine, particularly focusing on airway and vascular inflammation, and the biology of the innate immune system. We study the roles of TLRs in airway and vascular inflammation, using TLR agonists and natural viral pathogens. We are interested in how diesel nanoparticulate pollution exacerbates airways disease. We are also interested in how airways inflammation is initiated, why people with lung disease are at greater risk of coronary vascular disease, and whether inflammation contributes to the biology of pulmonary arterial hypertension. We are developing new treatments for human TLR-induced inflammation, and setting up new models of inflammation in human volunteers to probe how inflammation might work and best be treated.

My work is funded by the Medical Research Council, the Wellcome Trust, Asthma UK, Heart Research UK, and the NIHR.  We are very grateful for all the support we receive.

Professional Activities

I am subspeciality lead for Asthma in the Sheffield Thoracic Institute.
I chair the Scientific Advisory Board of the Clinical Research Facility.
I serve on an MRC Funding Board.
I have established and lead a popular education meeting, focusing on managing difficult lung disease in the real world, using case-based teaching. The 2012 meeting will focus on PH, infection, cancer and asthma.

Key Publications

Selected publications from ~90 articles to date.

  1. Pellino-1 Selectively Regulates Epithelial Cell Responses to Rhinovirus. J Bennett, LR Prince, LC Parker, CA Stokes, HG de Bruin, M van den Berge, IH Heijink, MKB Whyte, and I Sabroe. Journal of Virology 2012, in press.
  2. Deficiency of TNF-related apoptosis-inducing ligand (TRAIL) exacerbates lung injury and fibrosis. EE McGrath, A Lawrie, HM Marriott, P Mercer, SS Cross, V Singleton, AAR Thompson, SR Walmsley, I Sabroe, R Chambers, DH Dockrell, and MKB Whyte. Thorax 2012, in press.
  3. IL-1β regulates CXCL8 release and influences disease outcome in response to Streptococcus pneumoniae, defining intercellular cooperation between pulmonary epithelial cells and macrophages. K Gascoyne, H Marriott, R Gowda, I Geary, M Nicklin, F Iannelli, G Pozzi, T Mitchell, M Whyte, I Sabroe, and D Dockrell. Infection and Immunity 2012, 80(3):1140-49. PMID 22158745.
  4. Aspire: assessing the spectrum of pulmonary hypertension identified at a referral centre. J Hurdman, R Condliffe, CA Elliot, C Davies, C Hill, J Wild, D Capener, P Sephton, N Hamilton, IJ Armstrong, A Lawrie, I Sabroe, M Akil, L O’Toole, and DG Kiely. European Respiratory Journal 2011, ePub. PMID 2185399.
  5. The roles of IL-1 and MyD88-dependent signalling in rhinovirus infection. CA Stokes, S Ismail, EP Dick, JA Bennett, SL Johnston, MR Edwards, I Sabroe (joint senior author), and LC Parker. Journal of Virology 2011, 85(15):7912-21. PMID 21593174.
  6. TNF-related apoptosis-inducing ligand (TRAIL) regulates inflammatory neutrophil apoptosis and enhances resolution of inflammation. EE McGrath, HM Marriott, A Lawrie, SE Francis, I Sabroe, SA Renshaw, DH Dockrell, MKB Whyte. Journal of Leukocyte Biology 2011, 90(5):855-65. PMID 21562052.
  7. Prolyl hydroxylase PHD3 is essential for hypoxic regulation of neutrophilic inflammation in humans and mice. SR Walmsley, E Chilvers, AA Thompson, K Vaughan, HM Marriott, LC Parker, S Parmar, G Shaw, M Schneider, I Sabroe, DH Dockrell, M Milo, C Taylor, RS Johnson, CW Pugh, PJ Ratcliffe, PH Maxwell, P Carmeliet, and MKB Whyte. Journal of Clinical Investigation 2011, 123(3):1053-63. PMID 21317538.
  8. Effective caspase inhibition blocks neutrophil apoptosis and reveals Mcl-1 as both a regulator and a target of neutrophil caspase activation. D Wardle, J Burgon, I Sabroe, CD Bingle, MKB Whyte, and SA Renshaw. PLoS ONE 2011, 6;6(1):e15768. PMID 21253591.
  9. Temporal IL-1β secretion from primary human peripheral blood monocytes by P2X7-independent and P2X7-dependent mechanisms. JR Ward, SE Francis, PW West, MP Ariaans, LC Parker, DC Crossman, I Sabroe, and HL Wilson. Journal of Biological Chemistry 2010, 285(30):23147-58. PMID: 20495003.
  10. Diesel exhaust nanoparticles override natural injury-limiting pathways in the lung. N Chaudhuri, C Paiva, K Donaldson, R Duffin, LC Parker, and I Sabroe. American Journal of Lung Cell Molecular Physiology 2010, 299(2):L263-71. PMID: 20435687.
  11. A phosphatidylserine species inhibits a range of TLR, but not IL-1β, induced inflammatory responses by disruption of membrane microdomains. LC Parker, EC Prestwich, JR Ward, E Smythe, A Berry, M Triantafilou, K Triantafilou and I Sabroe. Journal of Immunology 2008, 181(8):5606-5617. PMID: 18832719.
  12. Ex-vivo expanded BM CD34+ cells have limited bactericidal ability. EP Dick, LR Prince, I Sabroe. Stem Cells 2008, 26:2552-2563. PMID: 18669908.
  13. Elevated CCR6(+) CD4(+) T lymphocytes in tissue compared with blood and induction of CCL20 during the asthmatic late response. JN Francis, I Sabroe, CM Lloyd, SR Durham and SJ Till. Clinical and Experimental Immunology 2008, 152(3):440-447. PMID: 18422729.
  14. Pathological networking: a new approach to understanding COPD. I Sabroe, LC Parker, PMA Calverley, SK Dower, MKB Whyte. (Review) Thorax 2007, 62(8):733-738. PMID: 17687100.
  15. Identifying and hurdling obstacles to translational research. I Sabroe, DH Dockrell, SN Vogel, SA Renshaw, MKB Whyte, and SK Dower. (Opinion) Nature Reviews Immunology 2007, 7(1):77-82. PMID: 17186032.
  16. Pulmonary Perspective: targeting the networks that underpin contiguous immunity in asthma and COPD. I Sabroe, LC Parker, DH Dockrell, SK Dower, and MK Whyte. (Perspective) American Journal of Respiratory and Critical Care Medicine 2007, 175(4):306-311. PMID: 17138954.
  17. Cooperative molecular and cellular networks regulate Toll-like receptor-dependent inflammatory responses. GE Morris, LC Parker, JR Ward, EC Jones, MKB Whyte, CE Brightling, P Bradding, SK Dower, and I Sabroe. FASEB Journal 2006, 20(12):2153-2155. PMID: 16935934.
  18. Agonists of Toll-like receptors 2 and 4 activate airway smooth muscle via mononuclear leukocytes. GE Morris, MKB Whyte, GF Martin, PJ Jose, SK Dower, and I Sabroe. American Journal of Respiratory and Critical Care Medicine 2005;171(8):814-822. PMID: 15657467.
  19. The role of IL-1β in direct and Toll-like receptor 4-mediated neutrophil activation and survival. LR Prince, L Allen, EC Jones, PG Hellewell, SK Dower, MKB Whyte and I Sabroe. American Journal of Pathology 2004;165:1819-1826. PMID: 15509550.
  20. Toll-like Receptor 2 and 4 Agonists Regulate C-C Chemokine Receptor-1 (CCR1) Expression in Monocytes. LC Parker, MKB Whyte, SN Vogel, SK Dower and I Sabroe. Journal of Immunology 2004;172:4977-4986. PMID: 15067079.
  21. Variations in eosinophil chemokine responses: an investigation of CCR1 and CCR3 function, expression in atopy, and identification of a functional CCR1 promoter. RM Phillips, VEL Stubbs, MR Henson, TJ Williams, JE Pease and I Sabroe. Journal of Immunology 2003;170:6190-6201. PMID: 12794150.
  22. Selective roles for TLR2 and TLR4 in the regulation of neutrophil activation and lifespan. I Sabroe, LR Prince, EC Jones, MJ Horsburgh, SJ Foster, SN Vogel, SK Dower and MKB Whyte. Journal of Immunology 2003;170:5268-5275. PMID: 12734376.
  23. Indomethacin causes PGD2-like and eotaxin-like selective responses in eosinophils and basophils VEL Stubbs, P Schratl, A Hartnell, TJ Williams, BA Peskar, A Heinemann & I Sabroe. Journal of Biological Chemistry 2002;277:26012-26020. PMID: 11980903.
  24. Responses of leukocytes to chemokines in whole blood and their antagonism by novel CCR3-specific small molecule inhibitors. S Bryan, PJ Jose, JR Topping, R Wilhelm, C Soderberg, D Kertesz, PJ Barnes, TJ Williams, TT Hansel & I Sabroe. American Journal of Respiratory and Critical Care Medicine 2002;165:1602-1609. PMID: 12070060.
  25. Toll-like receptor (TLR)2 and TLR4 in human peripheral blood granulocytes: a critical role for monocytes in leukocyte lipopolysaccharide responses. I Sabroe, EC Jones, LR Usher, MKB Whyte & SK Dower. Journal of Immunology 2002;168:4701-4710. PMID: 11971020.
  26. T cell phenotypes of the normal nasal mucosa: induction of Th2 cytokines and CCR3 expression by IL-4. SJ Till, LA Jopling, PA Wachholz, RL Robson, S Qin, DP Andrew, L Wu, J van Neerven, TJ Williams, SR Durham & I Sabroe. Journal of Immunology 2001; 166:2303-2310. PMID: 11160286.
  27. A small molecule antagonist of the chemokine receptors CCR1 and CCR3: potent inhibition of eosinophil function and CCR3-mediated HIV-1 entry. I Sabroe, MJ Peck, B Jan Van Keulen, A Jorritsma, G Simmons, PR Clapham, TJ Williams and JE Pease. Journal of Biological Chemistry 2000;275:25985-25992. PMID: 10854442.
  28. Differential regulation of eosinophil chemokine signalling via CCR3 and non-CCR3 pathways. I Sabroe, A Hartnell, LA Jopling, S Bel, P Ponath, J Pease, PD Collins & TJ Williams. Journal of Immunology 1999;162:2946-2955. PMID: 10072545.
  29. Cloning and characterisation of the Guinea-pig eosinophil eotaxin receptor, CCR3: blockade using a monoclonal antibody in vivo. I Sabroe, DM Conroy, NP Gerard, Y Li, PD Collins, TW Post, PJ Jose, TJ Williams, CJ Gerard & PD Ponath. Journal of Immunology 1998;161:6139-6147. PMID: 9834099.
  30. Chemoattractant cross-desensitisation of the human neutrophil interleukin-8 receptor involves receptor internalisation and differential receptor subtype regulation. I Sabroe, TJ Williams, CA Hébert & PD Collins. Journal of Immunology 1997;158: 1361-1369. PMID: 9013980.