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    • Dr Wuding Zhou Department of Nephrology and Transplantation MRC Centre for Transplantation 5th Floor, Tower Wing Guy's Hospital London SE1 9RT Tel 0207 1881528 Fax 0207 1885660 e-mail wuding.zhou@kcl.ac.uk Personal details Present Post: Reader in Immunology Nationality: British Education 1990-1995 PhD, United Medical and Dental Schools, Guy’s Hospital, University of London 1978-1983 MB, Huaxi University of Medicine, China Posts held 2009-present Reader in Immunology, King’s College London 2006-2009 Senior Lecturer, King’s College London 2000-2006 Lecturer, King’s College London 1995-1999 Post-doctoral Research Fellow, UMDS, Guy’s Hospital, London 1990-1995 RA, United Medical and Dental Schools, Guy’s Hospital, London 1983-1990 RA, Chengdu Institute of Biological Products, China Major research activities • Identified the cells and components involved in intra-renal synthesis of complement and their association with renal diseases and transplant rejection. • Demonstrated that inappropriate activation of the complement system is a pathogenic mediator of renal ischemia/reperfusion I/R injury and proposed an important role for C5b-9 formation and the alternative pathway of complement cascade in this model. • Found that complement and P-selectin-mediated pathways of renal reperfusion injury are mutually independent, suggesting that complement and P-selectin pose two distinct targets for therapy (at intravascular and extravascular sites, respectively) clarifying future strategies for preventing transplant injury in clinical translation. • Demonstrated that local synthesis of complement significantly contributes to the pathogenesis of proximal tubular epithelial cell damage in renal I/R injury. • Established a novel strategy of intragraft delivery of membrane-localizing complement regulator to increase the number of successful transplants in a pre-clinical model. • Reported that APCs from C3-/- mice have impaired potency to stimulate antigen-specific T cells. • Described remarkable finding that murine dendritic cells (DCs) are able to synthesise C3 (as well as other complement components) and how this is critical for DC functional development. • Explored the mechanisms by which complement regulate DC function. We demonstrated that local production and activation of complement up-regulates the allostimulatory function of DCs by C3a-C3aR interaction. • Identified the cyclic AMP (cAMP)-protein kinase A (PKA) signalling pathway through which C3a-C3aR interaction modulates DC function by enhancing their antigen uptake and surface molecule expression. 1
    • Awarded Grants 1. Analysis of the role of complement in immune complex glomerulonephritis: a study in C4 deficient mice S. H. Sacks, N. Sheerin, W. Zhou National Kidney Research Fund, 1995-1997 £64,909 2. The role of complement in renal inflammation W. Zhou Guy’s Special Trustees, 1997- 1998 £46,177 3. Urinary C3 as an index of chronic renal transplant rejection in man S. H. Sacks, W. Zhou and Robert Vaughan Guy’s & St Thomas’ Charitable Foundation, 2002 –2005 £133,000 4. Complement activation pathways in renal ischemia/reperfusion injury W. Zhou and S. H. Sacks The Wellcome Trust, 2002 –2005 £180,123 5. The study of anti-C5 mAb for the prevention of mice from renal ischemia reperfusion injury W. Zhou and S. H. Sacks Alexion Pharmaceuticals Inc, 2004-2005 £46,000 6. MRC PhD Studentship held by K. Anderson 2004-2007 £56,000 7. Role of the lectin activation pathway of complement in renal reperfusion injury and transplantation W. Schwaeble, S. Sacks, R. Sim, W. Zhou The Wellcome Trust, 2006 –2009 £443,321 8. Targeting the complement system in transplantation S. Sacks, W. Zhou, G. Lombardi MRC, 2007-2012 £1,276,863 10. Prevention of hyperacute rejection by intra-graft delivery of membrane localising complement regulator S. Sacks and W. Zhou The Wellcome Trust, 2007-2010 £233,647 11. Receptors for C3a and C5a modify dendritic cell function in alloreactive T cell responses and allograft rejection W. Zhou and S. Sacks MRC, 2007-2010 £561,662 PhD supervision: • PhD supervision 1999-2005: Tony Farrar 2000-2006: Hetal Patel 2004-2008: Katie Anderson • PhD examiner 2005: at Cardiff University (Lisa Clayton) • Being a member of the Divisional Postgraduate Training Committee • Regularly chairing PhD thesis progress committee meetings for PhD students 2
    • Undergraduate Teaching: 2007- present: [BSc] Lectured in Cell & Tissue Pathology- Immunology course: Innate Resistance Standing in the profession Invited lectures • Invited talk at Shanghai University of Medical Sciences, (2002): Role of complement in reperfusion injury. • Invited talk at Zhejiang College of Traditional Chinese Medicine (2002): Complement as a mediator of inflammatory damage. • Invited lecture at Royal Society of Medicine, London, March (2005): In programme “Bench- to-bedside innate immunity in transplantation”, Talk title: Complement and ischemia reperfusion injury contributes to organ damage. • Invited lecture at Nephrologist training schemes (UCL 2000). Session chair • XXI International Complement Work Shop (2006) Refereeing activities • Nephrology Dialysis Transplantation (2002, ref 01225) • J. Am. Soc. Nephrol. (2002, ref 12-0972) • Clinical Experimental Immunology (2005, ref 0955) • International Immunopharmacology (2005) • United States-Israel Binational Science Foundation (2005, ref200521) • Blood (2006, BLOOD/2006/063636) • Human immunology (2007, HIM-D-07-00041) • Molecular Immunology (2007, MIMM-D-07-00266) • Hong Kong Journal of Nephrology (2009, ref 08A352) 3
    • Publications Research articles 1. Synergy between type 1 fimbriae expression and C3 opsonisation increases internalisation of E. coli by human tubular epithelial cells. Li K, Zhou W, Hong Y, Sacks SH, Sheerin NS. BMC Microbiol. 9:64, 2009. 2. Li K., Anderson J.K., Peng Q., Noble A., Lu B., Kelly P.A., Wang N., Sacks S.H. and Zhou W., Cyclic AMP plays a critical role in C3a-receptor mediated regulation of dendritic cells in antigen uptake and T cell stimulation. Blood, 112:5084-94, 2008. 3. Peng, Q., K. Li, K. Anderson, C. A. Farrar, B. Lu, R. A. Smith, S. H. Sacks, and W. Zhou. Local production and activation of complement up-regulates the allostimulatory function of dendritic cells through C3a-C3aR interaction. Blood, 111:2452, 2008. 4. Peng, Q., K. Li, H. Patel, S. H. Sacks, and W. Zhou. Dendritic Cell Synthesis of C3 Is Required for Full T Cell Activation and Development of a Th1 Phenotype. J. Immunol. 176:3330, 2006. 5. Zhou, W., H. Patel, K. Li, Q. Peng, M. B. Villiers, and S. H. Sacks. Macrophages from C3- deficient mice have impaired potency to stimulate alloreactive T cells. Blood 107:2461, 2006. 6. Patel, H., R. A. Smith, S. H. Sacks, and W. Zhou. Therapeutic strategy with a membrane- localizing complement regulator to increase the number of usable donor organs after prolonged cold storage. J. Am. Soc. Nephrol. 17:1102.24, 2006. 7. Brown, K. M., E. Kondeatis, R. W. Vaughan, S. P. Kon, C. K. Farmer, J. D. Taylor, X. He, A. Johnston, C. Horsfield, B. J. Janssen, P. Gros, W. Zhou, S. H. Sacks, and N. S. Sheerin. Influence of donor C3 allotype on late renal-transplantation outcome. N. Engl. J. Med. 354:2014, 2006. 8. Farrar, C. A., W. Zhou, T. Lin, and S. H. Sacks. Local extravascular pool of C3 is a determinant of postischemic acute renal failure. FASEB J. 20:217, 2006. 9. Lin, T., W. Zhou, C. A. Farrar, R. E. Hargreaves, N. S. Sheerin, and S. H. Sacks. Deficiency of c4 from donor or recipient mouse fails to prevent renal allograft rejection. Am. J. Pathol. 168:1241, 2006. 10. Turnberg, D., M. Botto, M. Lewis, W. Zhou, S. H. Sacks, B. P. Morgan, M. J. Walport, and H. T. Cook. CD59a deficiency exacerbates ischemia-reperfusion injury in mice. Am. J. Pathol. 165:825, 2004. 11. 10. Tang, S., J. C. Leung, L. Y. Chan, A. W. Tsang, C. X. Chen, W. Zhou, K. N. Lai, and S. H. Sacks. Regulation of complement C3 and C4 synthesis in human peritoneal mesothelial cells by peritoneal dialysis fluid. Clin. Exp. Immunol. 136:85, 2004. 12. Li, K., H. Patel, C. A. Farrar, R. E. Hargreaves, S. H. Sacks, and W. Zhou. 2004. Complement activation regulates the capacity of proximal tubular epithelial cell to stimulate alloreactive T cell response. J. Am. Soc. Nephrol. 15:2414, 2004. 13. Farrar, C. A., Y. Wang, S. H. Sacks, and W. Zhou. Independent pathways of p-selectin and complement-mediated renal ischemia/reperfusion injury. Am. J. Pathol. 164:133, 2004. 14. Pratt, J. R., M. E. Jones, J. Dong, W. Zhou, P. Chowdhury, R. A. Smith, and S. H. Sacks. Nontransgenic hyperexpression of a complement regulator in donor kidney modulates transplant ischemia/reperfusion damage, acute rejection, and chronic nephropathy. Am. J. Pathol. 163:1457, 2003. 4
    • 15. Zhou, W., Y. Hong, K. Li, and S. H. Sacks. Triptolide is a potent suppressant of C3, CD40 and B7h expression in activated human proximal tubular epithelial cells. Kidney Int. 62:1291, 2002. 16. Zhou W., Sacks S.H., Complement and renal ischemia-reperfusion injury (Author reply). Am. J. Kidney Dis. 38:430-436, 2001. 17. Zhou, W., C. A. Farrar, K. Abe, J. R. Pratt, J. E. Marsh, Y. Wang, G. L. Stahl, and S. H. Sacks. Predominant role for C5b-9 in renal ischemia/reperfusion injury. J. Clin. Invest 105:1363, 2000. 18. Pratt, J. R., K. Abe, M. Miyazaki, W. Zhou, and S. H. Sacks. In situ localization of C3 synthesis in experimental acute renal allograft rejection. Am. J. Pathol. 157:825, 2000. 19. Gruden, G., S. Thomas, D. Burt, W. Zhou, G. Chusney, L. Gnudi, and G. Viberti. Interaction of angiotensin II and mechanical stretch on vascular endothelial growth factor production by human mesangial cells. J. Am. Soc. Nephrol. 10:730, 1999. 20. Tang, S., N. S. Sheerin, W. Zhou, Z. Brown, and S. H. Sacks. Apical proteins stimulate complement synthesis by cultured human proximal tubular epithelial cells. J. Am. Soc. Nephrol. 10:69, 1999. 21. Tang, S., W. Zhou, N. S. Sheerin, R. W. Vaughan, and S. H. Sacks. Contribution of renal secreted complement C3 to the circulating pool in humans. J. Immunol. 162:4336, 1999. 22. Song, D., W. Zhou, S. H. Sheerin, and S. H. Sacks. Compartmental localization of complement component transcripts in the normal human kidney. Nephron 78:15, 1998. 23. Zhou, W., O. Sasaki, M. Miyazaki, K. Abe, T. Koji, P. Verroust, S. Tsukasaki, Y. Ozono, T. Harada, P. K. Nakane, S. Kohno, and S. H. Sacks. Intraglomerular C3 synthesis in rats with passive Heymann nephritis. Am. J. Pathol. 151:1249, 1997. 24. Zhou, W., P. A. Andrews, Y. Wang, J. Wolff, J. Pratt, B. R. Hartley, P. Verroust, and S. H. Sacks. Evidence for increased synthesis of complement C4 in the renal epithelium of rats with passive Heymann nephritis. J. Am. Soc. Nephrol. 8:214, 1997. 25. Sheerin, N. S., W. Zhou, S. Adler, and S. H. Sacks. TNF-alpha regulation of C3 gene expression and protein biosynthesis in rat glomerular endothelial cells. Kidney Int. 51:703, 1997. 26. Andrews, P. A., J. E. Finn, C. M. Lloyd, W. Zhou, P. W. Mathieson, and S. H. Sacks. Expression and tissue localization of donor-specific complement C3 synthesized in human renal allografts. Eur. J. Immunol. 25:1087, 1995. 27. Andrews, P. A., A. Pani, W. Zhou, and S. H. Sacks. Local transcription of complement C3 in human allograft rejection. Evidence for a pathogenic role and correlation to histology and outcome. Transplantation 58:637, 1994. 28. Sacks, S. H., W. Zhou, P. A. Andrews, and B. Hartley. Endogenous complement C3 synthesis in immune complex nephritis. Lancet 342:1273, 1993. 29. Sacks, S., W. Zhou, R. D. Campbell, and J. Martin. C3 and C4 gene expression and interferon- gamma-mediated regulation in human glomerular mesangial cells. Clin. Exp. Immunol. 93:411, 1993. 30. Sacks, S. H., W. Zhou, A. Pani, R. D. Campbell, and J. Martin. Complement C3 gene expression and regulation in human glomerular epithelial cells. Immunology 79:348, 1993. 31. Zhou, W., R. D. Campbell, J. Martin, and S. H. Sacks. Interferon-gamma regulation of C4 gene expression in cultured human glomerular epithelial cells. Eur. J. Immunol. 23:2477, 1993. 5
    • Review articles 32. Peng Q., Li K., Sacks S.H., Zhou W. The role of anaphylatoxins C3 and C5a in regulating innate and adaptive immune responses. Inflammation and Allergy-Drug Target. 8:236-462009, 2009. 33. Zhou W., Lalli P.N., Sacks S., Medof M. E. and Heeger P.S., Locally produced and activated complement as a mediator of alloreactive T cell immunity. Front Biosci (Schol Ed). 1:117-24, 2009. 34. Sacks, S., Lee Q., Wong W., Zhou W., The role of complement in regulating the alloresponse. Curr. Opin. Organ Transplant. 14:10, 2009. 35. Sacks S.H., Zhou W., New Boundaries for Complement in Renal Disease. J Am Soc Nephrol 19:1865-1869, 2008. 36. Zhou,W., Peng,Q., Li,K., and Sacks,S.H. Role of dendritic cell synthesis of complement in the allospecific T cell response. Mol. Immunol. 44:57-63, 2007. 37. Zhou W., Medof M.E., Heeger P.S., Sacks S., Graft-derived complement as a mediator of transplant injury. Curr. Opin. Immunol. 19:569-576, 2007. 38. Zhou W., Sacks S.H., Complement in renal transplantation. Chapter in Complement and Kidney Diseases. Publisher: Birkhäuser. Editor: Peter F. Zipfel, 19-35, 2005. 39. Sacks S.H., Zhou W., Allograft rejection: effect of local synthesis of complement. Springer Semin Immunopathol. 27: 332-344, 2005. 40. Chowdhury P., Zhou W., Sacks S.H., Complement in renal transplantation. Nephron Clin Pract. 95(1):C3-8, 2003. 41. Sacks S.H., Chowdhury P., Zhou W., Role of the complement system in rejection. Current Opinion in Immunol. 15:487-492, 2003. 42. Sacks S.H., Zhou W., Locally produced complement and its role in renal allograft rejection. Am. J. Transplantation 3:927-932, 2003. 43. Sacks S.H., Zhou W., The effect of locally synthesised complement on acute renal allograft rejection. J. Molecular Medicine 81:404-410, 2003. 44. Zhou W., Marsh J., Sacks S.H., Intrarenal synthesis of complement. Kidney Int. 59:1227-1235, 2001. 45. Marsh J.E., Zhou W., Sacks S.H., Local tissue complement synthesis-fine tuning a blunt instrument. Archivum Immunologiae et Trerapiae Experimentalis 49:S41-S46, 2001. 46. Sacks S.H., Zhou W., Sherrin N.S. Local complement biosynthesis: Does in have a role in glomerulonephritis? J. Am. Soc. Nephrol. 7:2314-2319, 1996. 47. Andrew P.A., Zhou W., Sacks S.H., Tissue synthesis of complement as an immune regulator. Molecular Medicine Today. 4:202-207, 1995. 6