Professor Stephen A Renshaw MA FRCP PhD
Professor of Respiratory Medicine
Academic Unit of Respiratory Medicine
Department of Infection and Immunity
The University of Sheffield Medical School
Beech Hill Road
Tel: +44 (0)114 222 2334
Fax: +44 (0)114 271 3892
Secretary: Mrs Jenny Earl
Tel: +44 (0)114 226 1458
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.
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.
- I am lead for Respiratory Medicine Phase 2 and 2a and provide clinical input into respiratory teaching for Phase 1.
- I give lectures to Medical Students, MSc students and Biomedical Science students on inflammatory and infectious lung diseases, pleural disease, genetics of respiratory disease and non-mammalian models for the study of inflammation.
- Fellow of the Royal College of Physicians of London
- MRC Senior Clinical Fellow
- MRC Industry Partnership award Holder
- Clinical Subspeciality Lead for Pleural Disease, STHFT
- Associate board member NIHR Efficacy and Mechanisms Evaluation (EME) programme
- Reviewer of manuscripts and grant applications
- Identification of key regulatory pathways in neutrophil apoptosis and inflammation resolution
- Non-mammalian models of host-pathogen interaction
- Identification of novel compounds targeting inflammation resolution using zebrafish in vivo screens
For key publications see below. For a full list of publications click here.
- Hepburn L, Prajsnar TK, Klapholz C, Moreno P, Loynes CA, Ogryzko NV, Brown K, Schiebler M, Hegyi K, Antrobus R, Hammond KL, Connolly J, Ochoa B, Bryant C, Otto M, Surewaard B, Seneviratne SL, Grogono DM, Cachat J, Ny T, Kaser A, Török ME, Peacock SJ, Holden M, Blundell T, Wang L, Ligoxygakis P, Minichiello L, Woods CG, Foster SJ, Renshaw SA & Floto RA (2014) A Spaetzle-like role for nerve growth factor β in vertebrate immunity to Staphylococcus aureus. Science, 346(6209), 641-646.
- Candel S, de Oliveira S, López-Muñoz A, García-Moreno D, Espín-Palazón R, Tyrkalska SD, Cayuela ML, Renshaw SA, Corbalán-Vélez R, Vidal-Abarca I, Tsai HJ, Meseguer J, Sepulcre MP & Mulero V (2014) Tnfa signaling through tnfr2 protects skin against oxidative stress-induced inflammation.. PLoS Biol, 12(5), e1001855. View this article in White Rose Research Online
- Ogryzko NV, Renshaw SA & Wilson HL (2014) The IL-1 family in fish: swimming through the muddy waters of inflammasome evolution.. Dev Comp Immunol, 46(1), 53-62.
- McVicker G, Prajsnar TK, Williams A, Wagner NL, Boots M, Renshaw SA & Foster SJ (2014) Clonal expansion during Staphylococcus aureus infection dynamics reveals the effect of antibiotic intervention.. PLoS Pathog, 10(2), e1003959.
- Robertson AL, Holmes GR, Bojarczuk AN, Burgon J, Loynes CA, Chimen M, Sawtell AK, Hamza B, Willson J, Walmsley SR, Anderson SR, Coles MC, Farrow SN, Solari R, Jones S, Prince LR, Irimia D, Rainger GE, Kadirkamanathan V, Whyte MK & Renshaw SA (2014) A zebrafish compound screen reveals modulation of neutrophil reverse migration as an anti-inflammatory mechanism.. Sci Transl Med, 6(225), 225ra29.
- Burgon J, Robertson AL, Sadiku P, Wang X, Hooper-Greenhill E, Prince LR, Walker P, Hoggett EE, Ward JR, Farrow SN, Zuercher WJ, Jeffrey P, Savage CO, Ingham PW, Hurlstone AF, Whyte MK & Renshaw SA (2014) Serum and glucocorticoid-regulated kinase 1 regulates neutrophil clearance during inflammation resolution.. J Immunol, 192(4), 1796-1805.
- Ogryzko NV, Hoggett EE, Solaymani-Kohal S, Tazzyman S, Chico TJ, Renshaw SA & Wilson HL (2014) Zebrafish tissue injury causes upregulation of interleukin-1 and caspase-dependent amplification of the inflammatory response.. Dis Model Mech, 7(2), 259-264.
- Thompson AA, Elks PM, Marriott HM, Eamsamarng S, Higgins KR, Lewis A, Williams L, Parmar S, Shaw G, McGrath EE, Formenti F, Van Eeden FJ, Kinnula VL, Pugh CW, Sabroe I, Dockrell DH, Chilvers ER, Robbins PA, Percy MJ, Simon MC, Johnson RS, Renshaw SA, Whyte MK & Walmsley SR (2014) Hypoxia-inducible factor 2α regulates key neutrophil functions in humans, mice, and zebrafish.. Blood, 123(3), 366-376.
- Elks PM, Brizee S, van der Vaart M, Walmsley SR, van Eeden FJ, Renshaw SA & Meijer AH (2013) Hypoxia inducible factor signaling modulates susceptibility to mycobacterial infection via a nitric oxide dependent mechanism.. PLoS Pathog, 9(12), e1003789. View this article in White Rose Research Online
- Henry KM, Loynes CA, Whyte MK & Renshaw SA (2013) Zebrafish as a model for the study of neutrophil biology.. J Leukoc Biol, 94(4), 633-642.
- Feng Y, Renshaw S & Martin P (2012) Live Imaging of Tumor Initiation in Zebrafish Larvae Reveals a Trophic Role for Leukocyte-Derived PGE 2. Current Biology.
- Holmes GR, Anderson SR, Dixon G, Robertson AL, Reyes-Aldasoro CC, Billings SA, Renshaw SA & Kadirkamanathan V (2012) Repelled from the wound, or randomly dispersed? Reverse migration behaviour of neutrophils characterized by dynamic modelling.. J R Soc Interface, 9(77), 3229-3239. View this article in White Rose Research Online
- Santhakumar K, Judson EC, Elks PM, McKee S, Elworthy S, van Rooijen E, Walmsley SS, Renshaw SA, Cross SS & van Eeden FJ (2012) A zebrafish model to study and therapeutically manipulate hypoxia signaling in tumorigenesis.. Cancer Res, 72(16), 4017-4027.
- Prajsnar TK, Hamilton R, Garcia-Lara J, McVicker G, Williams A, Boots M, Foster SJ & Renshaw SA (2012) A privileged intraphagocyte niche is responsible for disseminated infection of Staphylococcus aureus in a zebrafish model.. Cell Microbiol, 14(10), 1600-1619.
- McGrath EE, Lawrie A, Marriott HM, Mercer P, Cross SS, Arnold N, Singleton V, Thompson AAR, Walmsley SR, Renshaw SA, Sabroe I, Chambers RC, Dockrell DH & Whyte MKB (2012) Deficiency of tumour necrosis factor-related apoptosis-inducing ligand exacerbates lung injury and fibrosis. Thorax, 67(9), 796-803.
- Renshaw SA & Trede NS (2012) A model 450 million years in the making: zebrafish and vertebrate immunity.. Dis Model Mech, 5(1), 38-47.
- Elks PM, Van Eeden FJ, Dixon G, Wang X, Reyes-Aldasoro CC, Ingham PW, Whyte MKB, Walmsley SR & Renshaw SA (2011) Activation of hypoxia-inducible factor-1α (hif-1α) delays inflammation resolution by reducing neutrophil apoptosis and reverse migration in a zebrafish inflammation model. Blood, 118(3), 712-722.
- Ward JR, Heath PR, Catto JW, Whyte MK, Milo M & Renshaw SA (2011) Regulation of neutrophil senescence by microRNAs.. PLoS One, 6(1), e15810. View this article in White Rose Research Online
- Gray C, Loynes CA, Whyte MK, Crossman DC, Renshaw SA & Chico TJ (2011) Simultaneous intravital imaging of macrophage and neutrophil behaviour during inflammation using a novel transgenic zebrafish.. Thromb Haemost, 105(5), 811-819. View this article in White Rose Research Online
- Loynes CA, Martin JS, Robertson A, Trushell DM, Ingham PW, Whyte MK & Renshaw SA (2010) Pivotal Advance: Pharmacological manipulation of inflammation resolution during spontaneously resolving tissue neutrophilia in the zebrafish.. J Leukoc Biol, 87(2), 203-212.
- Prajsnar TK, Cunliffe VT, Foster SJ & Renshaw SA (2008) A novel vertebrate model of Staphylococcus aureus infection reveals phagocyte-dependent resistance of zebrafish to non-host specialized pathogens.. Cell Microbiol, 10(11), 2312-2325.
- Mathew LK, Sengupta S, Kawakami A, Andreasen EA, Löhr CV, Loynes CA, Renshaw SA, Peterson RT & Tanguay RL (2007) Unraveling tissue regeneration pathways using chemical genetics.. J Biol Chem, 282(48), 35202-35210.
- Sabroe I, Dockrell DH, Vogel SN, Renshaw SA, Whyte MK & Dower SK (2007) Identifying and hurdling obstacles to translational research.. Nat Rev Immunol, 7(1), 77-82. View this article in White Rose Research Online
- Renshaw SA, Loynes CA, Trushell DM, Elworthy S, Ingham PW & Whyte MK (2006) A transgenic zebrafish model of neutrophilic inflammation.. Blood, 108(13), 3976-3978.
- Renshaw SA, Parmar JS, Singleton V, Rowe SJ, Dockrell DH, Dower SK, Bingle CD, Chilvers ER & Whyte MK (2003) Acceleration of human neutrophil apoptosis by TRAIL.. J Immunol, 170(2), 1027-1033. View this article in White Rose Research Online