Dr Phil Elks
Sir Henry Dale Fellow
Department of Infection, Immunity & Cardiovascular Disease
D31a, Firth Court
Sheffield S10 2TN
I graduated with a BSc (hons) in Biochemistry at the University of Warwick in 2004. I moved to Sheffield for the first time in 2004 to pursue a PhD in bone biology in a collaborative project between the, then newly forming, Centre for Developmental and Biomedical Genetics (CDBG) (with Dr Henry Roehl) and the Medical School (with Professor Peter Croucher), in which I studied the role of Wnt signalling in osteoblast formation in zebrafish. After my PhD I did a post-doctoral project with Dr Stephen Renshaw, in which I investigated hypoxia-induced genetic signalling (HIF signalling) and its role in inflammation. During this project I developed the zebrafish as a model to study HIF signalling, and I was awarded a European Respiratory Society (ERS) Long Term Fellowship in 2011 to study HIF’s role in infection. I moved to the University of Leiden, The Netherlands, to perform the ERS Fellowship, in which I found a role for HIF in the host-defence mechanism against Tuberculosis in a zebrafish model. In 2013 I was awarded a Vice-Chancellor’s Fellowship to return to Sheffield and set up my research group in Infection and Immunity. In 2015 I was awarded a Sir Henry Dale Fellowship from The Wellcome Trust/Royal Society.
When the body encounters invading pathogens, such as bacteria, a series of interactions between host immune cells and pathogen is initiated. These interactions are highly dynamic and involve complex genetic signalling pathways deriving from both the host and the pathogen. White blood cells, or leukocytes, of the host are able to phagocytose (internalise) bacteria and have an artillery of killing mechanisms to disarm the infection. However some bacteria, such as Mycobacterium tuberculosis, have evolved to survive and proliferate within host immune cells, disarming the leukocytes to make a niche in which to prosper. These types of infection have been historically successfully treated by targeting the bacteria using antibiotics. However, more recently, there has been an alarming rise in strains which are multi-drug resistant. Further understanding of the host response to infection is required to identify genetic targets for much needed future host-targetted therapies.
One host-genetic pathway that I have previously identified as being a modulator of both inflammation and infection is the HIF pathway, an important cellular oxygen sensing pathway. In the normal oxygen situation the HIF transcription factor is silenced by protein degradation, however during inflammatory and infection situations HIF is stabilised in leukocytes, via mechanisms that have yet to be fully elucidated, and has a number of immune activating effects. HIF therefore represents a potential host-derived target for therapeutics against infectious disease.
The zebrafish is my chosen model to study the roles of HIF in host response to infection. The zebrafish embryo is transparent and genetically manipulable, allowing a unique opportunity in which to study the host response to infection in a whole organism setting. Utilizing zebrafish models of infection I hope to shed light on the roles of HIF during infection, and to further understand the complex signalling processes involved in host-pathogen interaction.
- Vice-Chancellor’s Fellow.
- Member of the European Respiratory Society.
- Reviewer of manuscripts.
- Supervisor of students (BMedSci/ bachelors/ masters).
For Key Publications see below. For a full list of publications click here.
- Wiegertjes GF, Wentzel AS, Spaink HP, Elks PM & Fink IR (2016) Polarization of immune responses in fish: The ‘macrophages first’ point of view. Molecular Immunology, 69, 146-156.
- Felber K, Elks PM, Lecca M & Roehl HH (2015) Expression of osterix Is Regulated by FGF and Wnt/β-Catenin Signalling during Osteoblast Differentiation. PLOS ONE, 10(12). View this article in WRRO
- Elks PM, Renshaw SA, Meijer AH, Walmsley SR & van Eeden FJ (2015) Exploring the HIFs, buts and maybes of hypoxia signalling in disease: lessons from zebrafish models. Disease Models & Mechanisms, 8(11), 1349-1360.
- Ellett F, Elks PM, Robertson AL, Ogryzko NV & Renshaw SA (2015) Defining the phenotype of neutrophils following reverse migration in zebrafish. Journal of Leukocyte Biology, 98(6), 975-981.
- Elks PM, Van Der Vaart M, Van Hensbergen V, Schutz E, Redd MJ, Murayama E, Spaink HP & Meijer AH (2014) Mycobacteria counteract a TLR-mediated nitrosative defense mechanism in a zebrafish infection model. PLoS ONE, 9(6). View this article in WRRO
- Elks PM, van der Vaart M, Walmsley SR, van Eeden FJ, Spaink HP, Meijer AH & Renshaw SA (2014) Hypoxic signalling modulates neutrophil nitric oxide in a zebrafish tuberculosis model. EUROPEAN JOURNAL OF CLINICAL INVESTIGATION, 44, 12-12.
- 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 WRRO
- Harris JM, Esain V, Frechette GM, Harris LJ, Cox AG, Cortes M, Garnaas MK, Carroll KJ, Cutting CC, Khan T, Elks PM, Renshaw SA, Dickinson BC, Chang CJ, Murphy MP, Paw BH, Vander Heiden MG, Goessling W & North TE (2013) Glucose metabolism impacts the spatiotemporal onset and magnitude of HSC induction in vivo. Blood, 121(13), 2483-2493.
- Thompson AAR, 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 C, Johnson RS, Renshaw SA, Whyte MK & Walmsley SR (2013) Hypoxia-inducible factor 2α regulates key neutrophil functions in humans, mice and zebrafish. Blood, 123(3), 366-376.
- Santhakumar K, Judson EC, Elks PM, McKee S, Elworthy S, van Rooijen E, Walmsley SS, Renshaw SA, Cross SS & van Eeden FJM (2012) A zebrafish model to study and therapeutically manipulate hypoxia signaling in tumorigenesis.. Cancer Res, 72(16), 4017-4027.
- Kadirkamanathan V, Anderson SR, Billings SA, Zhang X, Holmes GR, Reyes-Aldasoro CC, Elks PM & Renshaw SA (2012) The neutrophil's eye-view: Inference and visualisation of the chemoattractant field driving cell chemotaxis in vivo. PLoS ONE, 7(4). View this article in WRRO
- Holmes GR, Dixon G, Anderson SR, Reyes-Aldasoro CC, Elks PM, Billings SA, Whyte MKB, Kadirkamanathan V & Renshaw SA (2012) Drift-Diffusion Analysis of Neutrophil Migration during Inflammation Resolution in a Zebrafish Model.. Adv Hematol, 2012, 792163. View this article in WRRO
- Dixon G, Elks PM, Loynes CA, Whyte MKB & Renshaw SA (2012) A method for the in vivo measurement of zebrafish tissue neutrophil lifespan.. ISRN Hematol, 2012, 915868. View this article in WRRO
- 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.
- Elks P, Dixon G, Wang X, Ingham PW, van Eeden FJ, Whyte M, Walmsley SR & Renshaw SA (2011) A Zebrafish Model Of Delayed Inflammation Resolution: Pharmacological And Genetic Activation Of The HIF1a Pathway. AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE, 183.
- Elks PM, Loynes CA & Renshaw SA (2011) Measuring inflammatory cell migration in the zebrafish.. Methods Mol Biol, 769, 261-275.
- Li N, Felber K, Elks P, Croucher P & Roehl HH (2009) Tracking gene expression during zebrafish osteoblast differentiation.. Dev Dyn, 238(2), 459-466.
Conference proceedings papers
- Thompson AAR, Elks PM, Marriott HM, Higgins KR, Parmar S, Shaw G, Eamsamarng S, McGrath EE, Formenti F, Van Eeden FJ, Kinnula VL, Pugh CW, Sabroe I, Dockrell DH, Chilvers ER, Robbins PA, Simon MC, Johnson RS, Renshaw SA, Whyte MKB & Walmsley SR (2012) HYPOXIA-INDUCIBLE FACTOR 2 alpha REGULATES NEUTROPHILIC INFLAMMATION IN HUMANS, MICE AND ZEBRAFISH. THORAX, Vol. 67 (pp A1-A1)
- Felber K, Elks P, Croucher P & Roehl H (2009) FGF signalling is regulating bone development in zebrafish. MECHANISMS OF DEVELOPMENT, Vol. 126 (pp S209-S209)
- Elks PM, Li N, Roehl HH & Croucher PI (2007) WNT signalling upregulates osteoblast differentiation in zebrafish: A novel model for studies in osteoblastogenesis. JOURNAL OF BONE AND MINERAL RESEARCH, Vol. 22(7) (pp 1115-1115)