The University of Sheffield
Department of Infection and Immunity

Dr Stephen A Renshaw MA FRCP PhD

Reader in Respiratory Medicine

renshaw

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

Tel:  +44 (0)114 222 2334
Fax: +44 (0)114 226 8898
Email: s.a.renshaw@sheffield.ac.uk
Secretary:  Mrs Jenny Earl
Tel:  +44 (0)114 226 8961
Email:  j.earl@sheffield.ac.uk

Biography

I have been with the University of Sheffield since 1998. I studied medical sciences at Cambridge before moving to Oxford, where I qualified as a doctor in 1994. After a clinical rotation in Nottingham, I passed the MRCP exam and moved to Sheffield to take up a Wellcome Trust Clinical Training Fellowship, to work on the role of death receptor signalling in the regulation of neutrophil lifespan in inflammation with Professor Moira Whyte. I was awarded my PhD in 2001, and became Clinical Lecturer in Respiratory Medicine. In 2004 I was awarded an MRC Clinician Scientist Fellowship, to develop a zebrafish model of inflammation, and I was appointed honorary consultant at the same time. I have been able to develop a unique neutrophil-specific transgenic zebrafish which has allowed several novel advances, and have developed the zebrafish as a model for inflammatory diseases. In 2008 I was awarded an MRC Senior Clinical Fellowship to continue these studies. We have a range of unique transgenic models in development, and have performed unbiased genetic and "chemical genetic" screens to help understand inflammation in vivo. In 2010 I was promoted to Reader.

Research Interests

Inflammatory diseases such as emphysema, asthma, heart disease and arthritis cause much illness in the developed world. We have little understanding of how the severe inflammation associated with something like pneumonia can completely resolve, while other sorts of inflammation persist with associated tissue damage. In fact, we know little of the processes that cause resolution of inflammation in any setting. There is considerable evidence that the main inflammatory cell, the neutrophil, turns itself off by a process called apoptosis (=programmed cell death), and is then recognised by macrophages and then removed. What triggers this process in neutrophils is not known. If we could find this out, we would be a step closer to understanding inflammatory disease, and might have new ideas about the sorts of treatments that might be successful. My work to date has studied these questions in primary human neutrophils, and I have particularly focused on the role of signaling through members of the Death Receptor family of proteins in regulating neutrophil lifespan. In order to fully explore the molecular events determining neutrophil lifespan, I have set up a model system in which the genes controlling resolution of inflammation can be identified. The model I have chosen is the Zebrafish, which is both genetically manipulable and transparent, leading to easy visualisation of neutrophils during development. I am currently studying inflammation in this system, and characterising how it resolves. This model allows me to test the ability of a range of candidate genes to influence the resolution of inflammation, and additionally to screen for novel genes involved in this process. These studies aim to identify the genes important in the resolution of inflammation, and so understand how this is dysregulated in chronic inflammatory disease.

Teaching Interests

Professional Activities

Current Projects

Key Publications

  1. CXCL8 (Interleukin-8) dictates neutrophil recruitment and behavior in the zebrafish inflammatory response. de Oliveira S, Reyes-Aldasoro CC, Renshaw SA, Mulero V and Calado A. Journal of Immunology 2013.
  2. Harris JM, Harris LJ, Cox GC, Garnaas MK, Frechette GM, Cortes M, Carroll KJ, Esain V, Cutting CC, Khan T, Elks PM, Renshaw SA, Dickenson BC, Chang CJ, Murphy MP, Paw BH, Vander Heiden MG, Goessling W and North TE. Metabolic activity determines the timing and magnitude of HSC induction through stimulation of hif1-mediated gene regulation. Blood. 2013 Jan 22. [Epub ahead of print]
  3. Canton I, Massignani M, Patikarnmonthon N, Chierico L, Robertson J, Renshaw SA, Warren NJ, Madsen JP, Armes SP, Lewis AL, Battaglia G. Fully synthetic polymer vesicles for intracellular delivery of antibodies in live cells. FASEB J.2013 Jan;27(1):98-108. doi: 10.1096/fj.12-212183. Epub 2012 Oct 2.
  4. Holmes GR, Anderson SR, Dixon G, Robertson AL, Reyes-Aldasoro CC, Billings SA, Renshaw SA*, Kadirkamanathan V*. Repelled from the Wound, or Randomly Dispersed? Reverse Migration Behaviour of Neutrophils Characterised by Dynamic Modelling. J R Soc Interface. 2012 Dec 7;9(77):3229-39. *Joint Senior Author
  5. Pase L, Layton JE, Wittman C, Ellett F, Nowell CJ, Reyes-Aldasoro CC, Varma S, Rogers KL, Hall CJ, Keightley MC, Crosier PS, Grabher C, Heath JK, Renshaw SA, Lieschke GJ. Neutrophil-delivered myeloperoxidase dampens the hydrogen peroxide burst after tissue wounding in zebrafish. Current Biology 2012 Oct 9;22(19):1818-24.
  6. Santhakumar K, Judson E, Elks PM, Mckee S, Elworthy S, Walmsley SR, Renshaw SA, Cross SS and van Eeden FJ. A Zebrafish Model to Study and Therapeutically Manipulate Hypoxia Signaling in Tumorigenesis. Cancer Research. 2012 Aug 15;72(16):4017-27.
  7. Prajsnar TK, Hamilton R, Garcia-Lara J, McVicker G, Williams A, Boots M, Foster SJ, Renshaw SA. A privileged intraphagocyte niche is responsible for disseminated infection of Staphylococcus aureus in a zebrafish model. Cell Microbiol. 2012 Oct;14(10):1600-19.
  8. Feng Y, Renshaw SA, Martin P. Live Imaging of Tumor Initiation in Zebrafish Larvae Reveals a Trophic Role for Leukocyte-Derived PGE2. Current Biology. May 31 2012.
  9. Kadirkamanathan V, Anderson, SR, Billings SA, Zhang X, Holmes GR, Reyes-Aldasoro CC, Elks PM and Renshaw SA. The Neutrophil’s eye-view: inference and visualisation of the chemoattractant field driving cell chemotaxis in vivo. PLoSONE 2012;7(4):e35182.
  10. McGrath EE, Lawrie A, Marriott HM, Mercer P, Cross SS, Arnold N, Singleton V, Thompson AA, Walmsley SR, Renshaw SA, Sabroe I, Chambers RC, Dockrell DH, Whyte MK. Deficiency of TNF-Related Apoptosis Inducing Ligand (TRAIL) exacerbates lung injury and fibrosis. Thorax. 2012 Sep;67(9):796-803.
  11. Renshaw SA, and Trede NS. A model 450 million years in the making: zebrafish and vertebrate immunity. Dis Model Mech 2012 5(1), 38–47.
  12. Philip M Elks, Fredericus J. van Eeden, Giles Dixon, Xingang Wang, Constantino Carlos Reyes-Aldasoro, Philip W. Ingham, Moira K.B. Whyte, Sarah R. Walmsley, and Stephen A. Renshaw (2011).  Activation of Hif-1alpha delays inflammation resolution by reducing neutrophil apoptosis and reverse migration in a zebrafish inflammation model.  Blood. 21;118(3):712-22.
  13. Emma Colucci-Guyon, Stephen A Renshaw and Philippe Herbomel (2011).  Strategies of Professional Phagocytes in vivo: unlike Macrophages, Neutrophils Efficiently Engulf only Surface-Associated Microbes.  Journal of Cell Science.  15;124(Pt 18):3053-9. 
  14. McGrath, E.E. Marriott, H.M., Lawrie, A., Francis, S.E., Sabroe, I., Renshaw, S.A., Dockrell, D.H., and Whyte, M.K.B. (2011).  TNF-related apoptosis-inducing ligand (TRAIL) regulates inflammatory neutrophil apoptosis and enhances resolution of inflammation.  J Leukoc Biol.  10;1189/jlb.0211062
  15. David J. Wardle, Joseph Burgon, Ian Sabroe, Colin D. Bingle, Moira K.B. Whyte, Stephen A. Renshaw. Effective caspase inhibition blocks neutrophil apoptosis and reveals Mcl-1 as both a regulator and a target of neutrophil caspase activation. PLoS ONE 2011; 6(1): e15768.
  16. Jon R. Ward, Paul R. Heath, Marta Milo, James W. Catto, Moira K.B. Whyte, Stephen A. Renshaw. Regulation of neutrophil senescence by microRNAs. PLoS ONE 2011; 6(1): e15810.
  17. Caroline Gray, Catherine A. Loynes, Moira K.B. Whyte, David C. Crossman, Stephen A. Renshaw*, Timothy J. Chico*. Simultaneous intravital imaging of macrophage and neutrophil behaviour during inflammation using a novel transgenic zebrafish. Thombosis and Haemostasis 2011; 105(4). (*Joint senior author).
  18. Stephen A. Renshaw, Philip W. Ingham. Zebrafish models of the immune response: taking it on the Chln. BMC Biology 2010; 8(1): 148.
  19. Catherine A. Loynes, Jane S. Martin, Anne L. Robertson, Daniel M.I. Trushell, Philip W. Ingham, Moira K.B. Whyte, Stephen A. Renshaw. Pivotal Advance: Pharmacological manipulation of inflammation resolution during spontaneously resolving tissue neutrophilia in the zebrafish. Journal of Leukocyte Biology 2010; 87: 203-12.
  20. Annette C Vergunst, Annemarie H Meijer, Stephen A Renshaw, David O'Callaghan. Burkholderia cenocepacia creates an intra-macrophage replication niche in zebrafish embryos, followed by bacterial dissemination and establishment of systemic infection. Infection and Immunity 2010; 78(4): 1495-1508.
  21. Tomasz Prajsnar, Vincent Cunliffe, Simon Foster, Stephen A. Renshaw. A novel vertebrate model of Staphylococcus aureus infection reveals phagocyte dependent resistance of zebrafish to non-host specialised pathogens. Celllular Microbiology 2008; 10(11): 2312–2325.
  22. Ian Sabroe, David H. Dockrell, Stefanie N. Vogel, Stephen A. Renshaw, Moira K. B. Whyte and Steven K. Dower. Identifying and hurdling obstacles to translational research. Nature Reviews Immunology 2007; 7(1): 77-82.
  23. Lijoy K. Mathew, Sumitra Sengupta, Atsushi Kawakami, Eric, A. Andreasen, Christiane V. Löhr, Catherine A. Loynes, Stephen A. Renshaw, Randall T. Peterson, and Robert L. Tanguay. Unraveling Tissue Regeneration Pathways Using Chemical Genetics. Journal of Biological Chemistry 2007; 282(48): 35202-35210.
  24. Stephen A. Renshaw, Catherine A. Loynes, Daniel M.I. Trushell, Stone Elworthy, Philip W. Ingham, Moira K.B. Whyte. A transgenic zebrafish model of neutrophilic inflammation. Blood 2006; 108: 3976-3978 (Plenary paper).
  25. Stephen A. Renshaw, Jasvir S. Parmar, Vanessa Singleton, Sarah J. Rowe, David H. Dockrell, Steven K. Dower, Colin D. Bingle, Edwin R. Chilvers, and Moira K. B. Whyte. Acceleration of Human Neutrophil Apoptosis by TRAIL. Journal of Immunology 2003; 170(2): 1027-1033.
  26. Stephen A. Renshaw, Samantha J. Timmons, Vanessa Eaton, Lynne R. Usher, Mohammed Akil, Colin D. Bingle, Moira K.B. Whyte. Inflammatory neutrophils retain susceptibility to apoptosis mediated via the Fas death receptor. Journal of Leukocyte Biology 2000; 67: 662-668.