Professor Stephen A Renshaw
MA FRCP PhD
School of Medicine and Population Health
Head of Division of Clinical Medicine
Deputy Dean of School of Medicine and Population Health
Sir Arthur Hall Professor of Medicine
+44 114 215 9574
Full contact details
School of Medicine and Population Health
Room FU33, F Floor
The Medical School
Beech Hill Road
Sheffield
S10 2RX
- Profile
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For enquiries please contact - SMPH-West-Operational@sheffield.ac.uk
I have worked for the University of Sheffield since 1998. I am the Sir Arthur Hall Professor of Medicine and Director of the Bateson Centre - a large cross-faculty research centre (former MRC Centre, 40PIs, over 130 members and active grant funding of over £30m).
I have held important leadership roles in large cross-institution partnerships, including being founding director of an MRC Doctoral Training Partnership across 4 major civic universities of the North of England – highly regarded as a model for student-led, cross-institutional, innovative postgraduate research training. I also have national and International leadership roles through membership of REF 2021 sub-panel 1, and having been principal organiser of Neutrophil 2021 and the Zebrafish Disease Models meeting 2022.
I studied medicine at Cambridge and then at Oxford Clinical School. After a clinical rotation in Nottingham, I moved to Sheffield to take up a Wellcome Trust Clinical Research Training Fellowship, to work on the regulation of neutrophil lifespan with Professor Moira Whyte.
After 3 years as Clinical Lecturer in Respiratory Medicine, I was awarded an MRC Clinician Scientist Fellowship to develop an innovative model of neutrophil biology in the transparent, genetically-tractable larval zebrafish. I have been able to develop a number of unique transgenic zebrafish which have allowed several important advances in our understanding of inflammation biology and of host-pathogen interaction.
In 2008 I was awarded an MRC Senior Clinical Fellowship and in 2014 an MRC Programme Grant to continue this work. I continue clinical work in Respiratory Medicine with a special interest in Interstitial Lung Disease associated with a range of multisystem diseases.
- Research interests
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Diseases of immunity cause much illness in the developed world – on one hand we are beset by a range of antibiotic resistance bacterial infections, while on the other hand our immune systems are responsible for many the common diseases of ageing – heart disease, stroke and COPD.
Understanding the regulation of innate immune cells, neutrophils and macrophages, in infection and inflammation will help us tune the immune system to the exact level needed to cope with the current level of threat. More host defence to fight antibiotic-resistant organisms; less host defence to prevent lung damage in response to environmental pollutants.
To improve our understanding, I have set up a model system in which the genes controlling regulation of innate immune cell function can be identified. The model I have chosen is the Zebrafish, which is both genetically manipulable and transparent, leading to easy visualisation of immune cells during infection and inflammation.
This model allows me to test the ability of a range of candidate genes to influence host-pathogen interaction and the resolution of inflammation, and additionally to screen for novel genes involved in this process. At the same time, I can see every immune cell during the whole of an infection or an inflammatory episode, where necessary imaging intracellular signalling events in real-time.
The small size of our model also lends itself to drug screening and this has identified several potential new therapies for immune disease.
Current projects
- Identification of key regulatory pathways in inflammation resolution.
- Non-mammalian models of host-pathogen interaction.
- Identification of novel compounds targeting inflammation resolution using zebrafish in vivo screens.
- Publications
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Show: Featured publications All publications
Featured publications
Journal articles
- Blood vessel occlusion by Cryptococcus neoformans is a mechanism for haemorrhagic dissemination of infection. PLoS Pathogens, 18(4). View this article in WRRO
- Demonstration of the role of cell wall homeostasis in Staphylococcus aureus growth and the action of bactericidal antibiotics. Proceedings of the National Academy of Sciences, 118(44). View this article in WRRO
- Commensal bacteria augment Staphylococcus aureus infection by inactivation of phagocyte-derived reactive oxygen species. PLoS Pathogens, 17(9).
- Pioneer neutrophils release chromatin within in vivo swarms. eLife, 10. View this article in WRRO
- Neutrophils use selective autophagy receptor Sqstm1/p62 to target Staphylococcus aureus for degradation in vivo in zebrafish. Autophagy, 17(6), 1448-1457. View this article in WRRO
- Staphylococcus aureus cell wall structure and dynamics during host-pathogen interaction. PLoS Pathogens, 17(3). View this article in WRRO
- Human-specific staphylococcal virulence factors enhance pathogenicity in a humanised zebrafish C5a receptor model. Journal of Cell Science, 134(5).
- Deletion of cftr leads to an excessive neutrophilic response and defective tissue repair in a zebrafish model of sterile inflammation. Frontiers in Immunology, 11(1).
- Polymersomes eradicating intracellular bacteria. ACS Nano, 14(7), 8287-8298. View this article in WRRO
- The failure of microglia to digest developmental apoptotic cells contributes to the pathology of RNASET2-deficient leukoencephalopathy. Glia, 68(7), 1531-1545. View this article in WRRO
- Semaphorin 3F signaling actively retains neutrophils at sites of inflammation. Journal of Clinical Investigation, 130(6), 3221-3237. View this article in WRRO
- The autophagic response to Staphylococcus aureus provides an intracellular niche in neutrophils. Autophagy, 17(4), 888-902.
- Inhibition of ErbB kinase signalling promotes resolution of neutrophilic inflammation. eLife, 8. View this article in WRRO
- The CXCL12/CXCR4 signaling axis retains neutrophils at inflammatory sites in zebrafish. Frontiers in Immunology, 10. View this article in WRRO
- 15-keto-prostaglandin E2 activates host peroxisome proliferator-activated receptor gamma (PPAR-γ) to promote Cryptococcus neoformans growth during infection. PLoS Pathogens, 15(3). View this article in WRRO
- CFTR protects against Mycobacterium abscessus infection by fine-tuning host oxidative defenses. Cell Reports, 26(7), 1828-1840.e4. View this article in WRRO
- PGE2 production at sites of tissue injury promotes an anti-inflammatory neutrophil phenotype and determines the outcome of inflammation resolution in vivo. Science Advances, 4(9). View this article in WRRO
- Human skin commensals augment Staphylococcus aureus pathogenesis. Nature Microbiology, 3(8), 881-890. View this article in WRRO
- Reverse Migration of Neutrophils: Where, When, How, and Why?. Trends in Immunology, 37(5), 273-286.
- A Spaetzle-like role for nerve growth factor beta in vertebrate immunity to Staphylococcus aureus. SCIENCE, 346(6209), 641-646. View this article in WRRO
- Tnfa signaling through tnfr2 protects skin against oxidative stress-induced inflammation.. PLoS Biol, 12(5), e1001855.
- The IL-1 family in fish: swimming through the muddy waters of inflammasome evolution.. Dev Comp Immunol, 46(1), 53-62.
- Clonal expansion during Staphylococcus aureus infection dynamics reveals the effect of antibiotic intervention.. PLoS Pathog, 10(2), e1003959.
- A zebrafish compound screen reveals modulation of neutrophil reverse migration as an anti-inflammatory mechanism.. Sci Transl Med, 6(225), 225ra29.
- Serum and glucocorticoid-regulated kinase 1 regulates neutrophil clearance during inflammation resolution.. J Immunol, 192(4), 1796-1805.
- Zebrafish tissue injury causes upregulation of interleukin-1 and caspase-dependent amplification of the inflammatory response.. Dis Model Mech, 7(2), 259-264.
- Hypoxia inducible factor signaling modulates susceptibility to mycobacterial infection via a nitric oxide dependent mechanism.. PLoS Pathog, 9(12), e1003789.
- Zebrafish as a model for the study of neutrophil biology.. J Leukoc Biol, 94(4), 633-642.
- Repelled from the wound, or randomly dispersed? Reverse migration behaviour of neutrophils characterized by dynamic modelling.. J R Soc Interface, 9(77), 3229-3239.
- Neutrophil-delivered myeloperoxidase dampens the hydrogen peroxide burst after tissue wounding in zebrafish. Current Biology, 22(19), 1818-1824.
- A privileged intraphagocyte niche is responsible for disseminated infection of Staphylococcus aureus in a zebrafish model.. Cell Microbiol, 14(10), 1600-1619.
- Live Imaging of Tumor Initiation in Zebrafish Larvae Reveals a Trophic Role for Leukocyte-Derived PGE 2. Current Biology.
- Deficiency of tumour necrosis factor-related apoptosis-inducing ligand exacerbates lung injury and fibrosis.. Thorax, 67(9), 796-803.
- A model 450 million years in the making: zebrafish and vertebrate immunity.. Dis Model Mech, 5(1), 38-47.
- Simultaneous intravital imaging of macrophage and neutrophil behaviour during inflammation using a novel transgenic zebrafish.. Thromb Haemost, 105(5), 811-819.
- 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.
- Pivotal Advance: Pharmacological manipulation of inflammation resolution during spontaneously resolving tissue neutrophilia in the zebrafish.. J Leukoc Biol, 87(2), 203-212.
- 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.
- Identifying and hurdling obstacles to translational research.. Nat Rev Immunol, 7(1), 77-82.
- A transgenic zebrafish model of neutrophilic inflammation.. Blood, 108(13), 3976-3978.
- Acceleration of human neutrophil apoptosis by TRAIL.. J Immunol, 170(2), 1027-1033.
All publications
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- Blood vessel occlusion by Cryptococcus neoformans is a mechanism for haemorrhagic dissemination of infection. PLoS Pathogens, 18(4). View this article in WRRO
- Professional activities and memberships
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- Director, The Bateson Centre.
- Principal Organiser, Neutrophil in Immunity Meeting 2021 and Zebrafish Disease Models meeting 2022.
- Research Excellence Framework, subpanel 1.