Professor Paul Hellewell BSc PhD

Professor of Vascular Biology Faculty Director of Research & Innovation Address: Department of Cardiovascular Science University of Sheffield Medical School Beech Hill Road Sheffield S10 2RX Telephone: +44 (0)114 271 3231 Fax: +44 (0)114 271 1863 Email: p.g.hellewell@sheffield.ac.uk Secretary: Mr Steven Rowley Telephone: +44 (0)114 271 2052 Email: steven.rowley@sheffield.ac.uk

Biography:

I graduated in Pharmacology from King´s College, London in 1984 and studied for a PhD on prostaglandin and purine metabolism in the lung at the Institute of Animal Physiology, now the Babraham Institute, in Cambridge under the supervision of Jeremy Pearson. I then carried out 4 years postdoctoral research in Tim William´s lab, initially at the College of Surgeons in London and then at the MRC Clinical Research Centre, Northwick Park. This was followed by a 2 year postdoctoral fellowship (1998-1989) in Peter Henson´s lab at the National Jewish Centre for Immunology & Respiratory Medicine in Denver, Colorado. In 1990, I was Head of Cell Biology at British Biotechnology in Oxford before moving back into academia in late 1991 when I took up a Senior Lectureship in Applied Pharmacology at the National Heart & Lung Institute in London, now part of Imperial College. I took up my current post as Chair of Vascular Biology in the University of Sheffield Medical School in 1998. I am also Faculty Director of Research and Innovation, having held a number of senior roles (Director of the Division of Clinical Sciences North, Director of Resources and Acting Dean) in the Medical School.

Research Interests:

• Mechanisms and regulation of leukocyte endothelial transmigration.
• Biology of selectins and selectin ligands.

Current Projects:

• Regulation of monocyte-endothelial cell interactions by neutrophil-derived microparticles (2010-2012). British Heart Foundation Project Grant. Dr V. Ridger and Professor P. Hellewell.
• Effects of nociceptin on the microcirculation during sepsis. (2008-2011). British Heart Foundation PhD Studentship. Professor P. Hellewell and Dr V. Ridger.
• Regulation of lymphatic function in sepsis (Uzma Reem).
• Advanced imaging techniques to observe inflammatory events (with Drs Ridger, Gray and Arianns).
• Exploiting adhesion molecules for therapeutic gene targeting (with Dr C Newman).

Key Publications:

1. Newman CM, Crosdale DJ, Fisher KD, Briggs SS, Norman KE, Seymour LW, Hellewell PG. P-selectin dependent targeting to inflamed endothelium of recombinant P-selectin glycoprotein ligand-1 immunoglobulin chimera-coated poly[N-(2-hydroxypropyl) methacrylamide]-DNA polyplexes in vivo visualised by intravital microscopy. J Gene Med. 2009 Apr;11(4):326-34.
2. Abbitt KB, Cotter MJ, Ridger VC, Crossman DC, Hellewell PG, Norman KE. Antibody ligation of murine Ly-6G induces neutropenia, blood flow cessation, and death via complement-dependent and independent mechanisms. J Leukoc Biol. 2009 Jan;85(1):55-63.
3. Nolan S, Dixon R, Norman K, Hellewell P, Ridger V. Nitric oxide regulates neutrophil migration through microparticle formation. Am J Pathol. 2008 Jan;172(1):265-73.
4. Ridger VC, Hellewell PG, Norman KE. L- and P-selectins collaborate to support leukocyte rolling in vivo when high-affinity P-selectin-P-selectin glycoprotein ligand-1 interaction is inhibited. Am J Pathol. 2005 Mar;166(3):945-52.
5. Hicks AE, Abbitt KB, Dodd P, Ridger VC, Hellewell PG, Norman KE. The anti-inflammatory effects of a selectin ligand mimetic, TBC-1269, are not a result of competitive inhibition of leukocyte rolling in vivo. J Leukoc Biol. 2005 Jan;77(1):59-66.
6. Ali M, Hicks AE, Hellewell PG, Thoma G, Norman KE. Polymers bearing sLex-mimetics are superior inhibitors of E-selectin-dependent leukocyte rolling in vivo. FASEB J. 2004 Jan;18(1):152-4.
7. Hicks AE, Nolan SL, Ridger VC, Hellewell PG, Norman KE. Recombinant P-selectin glycoprotein ligand-1 directly inhibits leukocyte rolling by all 3 selectins in vivo: complete inhibition of rolling is not required for anti-inflammatory effect. Blood. 2003 Apr 15;101(8):3249-56.
8. Norman KE, Cotter MJ, Stewart JB, Abbitt KB, Ali M, Wagner BE, Wallace WA, Forlow SB, Hellewell PG. Combined anticoagulant and antiselectin treatments prevent lethal intravascular coagulation. Blood. 2003 Feb 1;101(3):921-8.
9. Hicks AE, Leppänen A, Cummings RD, McEver RP, Hellewell PG, Norman KE. Glycosulfopeptides modeled on P-selectin glycoprotein ligand 1 inhibit P-selectin-dependent leukocyte rolling in vivo. FASEB J. 2002 Sep;16(11):1461-2.
10. Ridger VC, Wagner BE, Wallace WA, Hellewell PG. Differential effects of CD18, CD29, and CD49 integrin subunit inhibition on neutrophil migration in pulmonary inflammation. J Immunol. 2001 Mar 1;166(5):3484-90.

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