Professor Paul Evans

Professor of Cardiovascular Science

Address:   Department of Cardiovascular Science University of Sheffield Medical School Beech Hill Road Sheffield S10 2RX Tel: +44 (0)114 271 2591 Fax: +44 (0)114 271 1863 Email: paul.evans@sheffield.ac.uk Secretary: Mr Steve Rowley Telephone: +44 (0)114 271 2052 Email: steven.rowley@sheffield.ac.uk

Biography:

I joined Dr Graeme Alexander's laboratory (Cambridge, UK) in 1993 to study the immunological processes that govern chronic rejection of liver grafts and graduated with a PhD in 1996. Following Post-doctoral positions in Prof. Lee Nelson's group at the Fred Hutchinson Cancer Research Center (Seattle, USA) and Dr. Peter Kilshaw's laboratory at the Babraham Institute (Cambridge, UK), I was awarded Training and Senior Fellowships by Kidney Research UK to study the intracellular signalling pathways that control inflammatory activation and injury of vascular endothelial cells. My studies in this field were recognized by the British Transplantation Society who awarded me the Medawar Prize in 2000. I joined Imperial College London in 2004 as a Senior Lecturer in Endothelial Cell Physiology and was promoted to Reader in 2010. During this time, I headed the Intracellular Signalling Laboratory within the British Heart Foundation Cardiovascular Sciences Unit, which is headed by Prof. Dorian Haskard. I was appointed to the Chair in Cardiovascular Science at the University of Sheffield in October 2011

Research Interests:

My research is focussed on the effects of shear stress (a mechanical force generated by flowing blood) on the physiology of vascular endothelial cells. These studies are relevant to vascular injury and atherosclerosis which develop predominantly at branches and bends in the arterial tree that are exposed to disturbed patterns of blood flow. The cross-disciplinary nature of my work has led to interactions with molecular and cellular biologists, vascular physiologists and bioengineers. My research program will improve our understanding of the molecular mechanisms that give rise to the spatial distribution of atherosclerotic plaques, and will inform novel therapeutic approaches to prevent or treat atherosclerosis by inducing protective molecules at atherosusceptible regions. My studies in this field have been recognized by the British Atherosclerosis Society (John French Lecture 2011) and the British Cardiovascular Society (Michael Davies Award 2011), and members of my group have also won prestigious prizes including the Promega UK Young Life Scientist Award in 2009 (Dr Kim Van der Heiden), the British Atherosclerosis Society Young Investigator Award in 2010 (Dr Simon Cuhlmann) and the Society for Cardiovascular Surgery in Great Britain and Ireland - Ronald Edwards Medal (Mr Mustafa Zakkar in 2010 and Mr Bao Nguyen in 2012).

Professional Activities:

• British Heart Foundation Project Grant Committee Member.
• British Atherosclerosis Society Committee Member.
• Board member of the European Society for Cardiology Working Group on Atherosclerosis and Vascular Biology.
• Board member of the European Association for Predictive, Preventative and Personalised Medicine.
• Rapporteur for the European Commission - Marie Curie Framework 7 (2010) and Marie Curie Framework 6 (2005).
• Senior Editor for the Journal of Inflammation (2009-) and Editorial Board member for numerous international journals.

Current Projects:

1. Identification of novel mechanoresponsive signalling networks that control endothelial cell injury and activation. Professor Evans principal applicant with Professor Henning Walczak, Dr Chuh K Chong and Dr Tim Chico. British Heart Foundation Funding.
2. The Influence of Shear Stress on Vascular Endothelial Cell Senescence. Professor Evans principal applicant with Dr Chong and Professor Qwarnstrom. British Heart Foundation Funding.
3. Does high shear stress suppress endothelial cell apoptosis at atheroprotected regions by inducing MAP kinase phosphatase-1? Professor Evans principal applicant with Professor Justin Mason (Imperial College London). British Heart Foundation Funding.
   
   

Key Publications:

1. Luong L, Fragiadaki M, Smith J, Boyle J, Lutz J, Dean JL, Harten S, Ashcroft M, Walmsley S, Haskard DO, Maxwell PH, Walczak H, Pusey C, Evans PC. (2013) Cezanne regulates inflammatory responses to hypoxia in endothelial cells by targeting TRAF6 for deubiquitination. Circ Res. [Epub ahead of print].


2. Van der Heiden K, Gijsen F, Narracott A, Hsiao S, Gunn J, Wentzel J, Evans P. (2013) The effects of stenting on shear stress: relevance to endothelial injury and repair. Cardiovascular Research [Epub ahead of print].


3. Cuhlmann S, Van der Heiden K, Saliba D, Tremoleda JL, Khalil M, Zakkar M, Chaudhury H, Luong LA, Mason JC, Udalova I, Gsell W, Jones H, Haskard DO, Krams R and Evans PC (2011). Disturbed blood flow induces RelA expression via c-Jun N-terminal kinase 1: a novel mode of NF-κB regulation that promotes arterial inflammation Circ. Res. 108(8), 950-959.


4. Zakkar M, Chaudhury H, Luong LA, Punjabi PP, Anderson JR, Mullholand JW, Clements AT, Krams R, Foin N, Leen ELS, Mason JC, Haskard DO and Evans PC (2011). Dexamethasone arterializes venous endothelial cells by inducing MAP kinase phosphatase-1: a novel anti-inflammatory treatment for vein grafts? Circulation 123 (5): 524-532.


5. Chaudhury H, Zakkar M, Boyle J, Cuhlmann S, van der Heiden K, Luong LA, Davis J, Platt A, Mason JC, Krams R, Haskard DO, Clark AR, and Evans PC (2010). c-Jun N-terminal kinase primes endothelial cells at atheroprone sites for apoptosis. Arterioscler. Thromb. Vasc. Biol. 30(3):546-53.


6. Zakkar M, Van der Heiden K, Luong LA,Chaudhury H, Cuhlmann S, Hamdulay SS, Krams R, Edirisinghe I, Rahman I, Carlsen H, Haskard DO, Mason JC, and Evans PC (2009) Activation of Nrf2 in endothelial cells protects arteries from exhibiting a pro-inflammatory state. Arterioscler. Thromb. Vasc. Biol. 29(11):1851-7


7. Zakkar, M., Chaudhury, H., Sandvik, G., Enesa, K., Luong, L.A., Cuhlmann, S., Mason, J.C., Krams, R., Clark, A.R., Haskard, D.O. and Evans, P.C. (2008) Increased endothelial MAP kinase phosphatase-1 expression suppresses pro-inflammatory activation at sites that are resistant to atherosclerosis. Circ. Res. 103, 726-732.


8. Lutz, J., Luong, L.A., Strobl, M., Deng, M., Huang, H., Anton, M., Enesa, K., Zakkar, M., Chaudhury, H., Haskard, D.O., Harten, S., Maxwell, P., Pusey, C., Heemann, U. and Evans, P.C. (2008) The A20 gene protects kidneys from ischaemia/ reperfusion injury by suppressing pro-inflammatory activation. J. Mol. Med. 86(12),1329-39.


9. Enesa, K., Ito, K., Thorbjornsen, I., Phua, C., To, Y., Haskard, D.O., Boyle, J., Adcock, I., and Evans, P.C. (2008) Hydrogen peroxide prolongs nuclear localisation of NF-κB in activated cells by suppressing negative regulatory mechanisms. J. Biol. Chem. 283(27):18582-18590.


10. Enesa, K., Zakkar, M., Chaudhury, H., Luong, L.A., Rawlinson, L., Mason, J.C., Haskard, D.O., Dean, J.L.E. and Evans, P.C. (2008) NF-κB suppression by the deubiquitinating enzyme Cezanne: a novel negative feedback loop in pro-inflammatory signaling. J. Biol. Chem. 283 (11), 7036-7045.


11. Partridge, J., Carlsen, H., Enesa, K., Chaudhury, H., Zakkar, M., Luong, L.A., Kinderlerer, A., Johns, M., Blomhoff, R., Mason, J.C., Haskard, D.O. and Evans, P.C. (2007) Shear stress acts as a switch to regulate divergent functions of NF-κB in endothelial cells: a potential novel mechanism for atheroprotection. FASEB J. 21 (13), 3553-3561

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