Dr Kevin Marchbank
Senior Lecturer in Complement Therapeutics
- Email: email@example.com
- Telephone: +44 (0) 191 208 5998
- Fax: +44 (0) 191 208 8988
- Address: Institute of Cellular Medicine
3rd Floor William Leech Building
The Medical School, Newcastle University
I am complement biologist and B cell immunologist with a focus on kidney and eye disease.
My research group is part of the newly formed Complement Therapeutics Research Group which includes the groups of Prof Claire Harris, Prof Neil Sheerin and Dr David Kavanagh.
We are a key component of the National Renal Complement Therapeutics Centre (NRCTC), RVI, Newcastle-upon-Tyne. Click here to see the NRCTC web pages
My current interests are the role of anti-complement protein autoantibodies in aHUS and C3G (MPGN). The development of Factor H based therapeutics, primarily for the treatment of C3G and aHUS. This sits along side a long standing interest in the role of CR2 in B cell function and the use of complement proteins as adjuvants in vaccine design.
1989-1993 Obtained an upper class 2 degree (2\1) in B.Sc. (Hons) Immunology from the University of Glasgow
1993- 97 Obtained Ph.D., based on “Cell resistance and recovery after complement attack: The role of CD59” under the supervision of Professor B. Paul Morgan & Dr Carmen W. van den Berg.
1997-2000 Awarded a prestigious Wellcome Trust prize international fellowship to generate human complement receptor 2 transgenic mice within Prof. V. Michael Holers laboratories in the Dept. of Medicine and Immunology, UCHSC, Denver, CO, USA.
2000-0ct 2002 In continuation of the Wellcome Trust Prize International Fellowship, I returned to Prof. B. Paul Morgan’s laboratories in Cardiff, Wales to fully develop my research on the hCR2 transgenic mice.
Oct 2002- Oct 2006 Obtained a Wellcome Trust research career development fellowship (RCDF), at the UWCM (now Cardiff University) where I established a small research group examining the links between the innate and the humoral immune systems and began to develop a strong interest in the role of novel molecular adjuvants such as C3d trimers or octamers in generating improved vaccination profiles and reagents.
Oct 2006-Dec 2008. Accepted a position as Lecturer in Medicine (nephrology) within the Institute of Human Genetics, Newcastle University where I developed an interest in the role of the immune system in atypical haemolytic ureamic syndrome and membranoproliferative glomerulonephritis.
Jan 2009 - present. Transferred within Newcastle University to the newly formed Institute of Cellular Medicine and the Applied Immunobiology grouping. I am now part of Inflammation, Immunology and Immunotherapy. Please see research for current ongoing projects.
Roles and Responsibilities
Group leader, research focus on the complement system, kidney and eye disease, vaccine adjuvants based on C3d, and the development of FH based therapeutics, see research.
Provide lectures and laboratory projects to all levels students at Newcastle University
Nov 2015 to present:- Head of Excellence in Learning and Teaching; ICM.
Co-Lead of ICM Equality and Fairness committee
Head of autoimmune aHUS research and analysis (NRCTC).
Doctor of Philosophy (Medical Biochemistry), UWCM, March 1997.
Diploma in Bio-Medical methods, UWCM, July 1994.
Bachelor of Science (2/1 hons) in Immunology, University of Glasgow, July 1993.
2002-2006, Wellcome Trust RCD fellow & Lecturer, Cardiff University
2000-2002, Wellcome Trust Fellow, University of Wales College of Medicine
1999 –2000 NIH Research Fellow, University of Colorado Health sciences center
1997- 1999, Wellcome Trust Prize travelling Fellow, University of Colorado Health sciences center
British Society for Immunology,
International Complement Society
aHUS Rare disease group of RADAR
MPGN/DDD/C3G Rare disease group of RADAR
Honours and Award
2002 Research Career Development Fellowship, The Wellcome Trust
1997 Prize International Travelling Fellowship, The Wellcome Trust
1993 PhD scholarship, University of Wales College of Medicine
Keen hiker, photographer, amateur artist and enjoy stimulating conversation, meeting new faces and as such have always enjoyed travel.
The complement system (Innate immunity), particularly Factor H, Factor H related proteins and C3 in both mouse and man.
Autoantibodies (in Kidney Diseases)
B cell development and the Humoral Immune response.C3d as a molecular adjuvant.
Transgenic mice and certain Immune response models, Autoantibody ELISA (specifically anti Factor H ). Complement factor H related proteins. C3 Glomerulopathy (C3G) or Membranoproliferative glomerulonephritis (MPGN) and atypical Haemolytic ureamic syndrome (aHUS).
>AutoAbs to Factor H . We have published several articles on the involvement of anti-Factor H autoantibodies in the development of aHUS and C3G.
>Understanding the function of complement factor H related proteins (FHRs) through the development of unique monoclonal antibodies and recombinant protein assays. We are working with Prof Mike Holers team in Denver Colorado to study the mouse FHRs and have recently investigated CFHL1 through funding from the NCKRF.
>Proof of concept funding looking at novel bacterial protein based adjuvants. C3d, a breakdown fragment of the complement protein C3, through its binding to complement receptor 2 has been shown to amplify the humoral immune response to antigen many fold. We are currently working on use of proteins designed to capture this function to aid vaccine delivery and potency we are also working with colleagues in Bath to improve vaccine transport. See our recent work in this area.
> anti-complement Therapeutics: Development of targeted factor H (FH) fusion proteins in order to protect the kidney from run away C activation. We are using existing (CR2-FH and Mini-FH) and novel strategies (homo-dimeric mini-FH) to target the C inhibitory domains of FH to the kidney (and the eye).
> C3 gain of function study: We have developed a unique C3 gain of function comparative model to investigate the mechanisms that pre-dispose to aHUS, the mechanisms that lead to pathology in the disease and to investigate treatment solutions, such as homo-dimeric mini-FH.
Pet project; examining the role of C3 and CR2 in the development of B cell tolerance
The role of complement in the development of AMD (development of novel models/treatments)
The development of new models of aHUS investigating the trigger and role of the coagulation pathway.
Lab based scientist, currently writing grants and papers. My Group currently consists of 3 technicians, 4 PhDs (primary and co supervised), 2 PDRAs and 1 Clinical fellow
Invited Tutor at the 16th European Meeting for Complement in Human Disease conference in Hungary september 2009.
Invited member of recently established MPGN (DDD) Rare Kidney diseases sub-group of the Renal association.
Founder member of Complement UK
Part of the International Complement Societies standardisation team with respect to development of a standard anti-FH autoantibody ELISA
MRC CiC and BBSRC Funding to develop a vaccine adjuvant for mTB.
NCKRF and Newcastle Healthcare Charities supporting work surrounding the C3 gain of function model
Kidney Research UK supporting the investigation of mini-FH in C3G; PhD trigger events in aHUS and Project grant looking at use of anti-complement drugs in complement mediated renal diseases
P031134GB "Modified Complement proteins and uses thereof"
P030973GB "Recombinant mature Complement Factor I"
1619965.5 "Immunogenic compositions comprising Sbi protein and use thereof" (with University of Bath)
MRes research project supervision
MRes Lecturer, Complement in Health and Disease
Undergraduate Teaching (B940/B900)
CMB3000 Undergraduate research project supervision
BMS3021 Lecture on complement in health and disease, provide seminar
BGM3039 Lecture on complement therapeutics
MIC3044 Provide seminar
- Yang Y, Denton H, Davies OR, Smith-Jackson K, Kerr H, Herbert A, Barlow PN, Pickering MC, Marchbank KJ. Homodimeric Minimal Factor H fusion proteins Ameliorate Experimental C3G with Improved In vivo Pharmacodynamics Compared To Mini-FH. Journal of the American Society of Nephrology 2018. In Press.
- Kerr H, Wong E, Makou E, Yang Y, Marchbank K, Kavanagh D, Richards A, Herbert A, Barlow P. Disease-linked mutations in factor H reveal pivotal role of cofactor activity in self surface-selective regulation of complement activation. Journal of Biological Chemistry 2017, Epub ahead of print.
- Brocklebank V, Johnson S, Sheerin TP, Marks SD, Gilbert RD, Tyerman K, Kinoshita M, Awan A, Kaur A, Webb N, Hegde S, Finlay E, Fitzpatrick M, Walsh P, Wong EKS, Booth C, Kerecuk L, Salama A, Almond M, Inward C, Goodship TH, Sheerin N, Marchbank KJ, Kavanagh D. Factor H autoantibody is associated with atypical hemolytic uremic syndrome in children in the United Kingdom and Ireland. Kidney International 2017, 92(5), Pages 1261-1271.
- Antonioli AH, White J, Crawford F, Renner B, Marchbank KJ, Hannan JP, Thurman JM, Marrack P, Holers VM. Modulation of the Alternative Pathway of Complement by Murine Factor H-Related Proteins. Journal of Immunology 2017, Epub ahead of print.
- Chen Y, Smith T, Hicks R, Doekhie A, Koumanov F, Wells S, Edler K, van-den-Elsen J, Holman G, Marchbank K, Sartbaeva A. Thermal stability, storage and release of proteins with tailored fit in silica. Scientific Reports 2017, (ePub ahead of Print).
- Challis RC, Ring T, Xu Y, Wong EKS, Flossmann O, Roberts ISD, Ahmed S, Wetherall M, Salkus G, Brocklebank B, Fester J, Strain L, Wilson V, Wood KM, Marchbank KJ, Santibanez-Koref M, Goodship THJ, Kavanagh D. Thrombotic Microangiopathy in Inverted Formin 2-Mediated Renal Disease. Journal of the American Society of Nephrology 2017, 28(4), 1084-1091.
- Challis RC, Araujo GSR, Wong EKS, Anderson HE, Awan A, Dorman AM, Waldron M, Wilson V, Brocklebank V, Strain L, Morgan BP, Harris CL, Marchbank KJ, Goodship THJ, Kavanagh D. A De Novo Deletion in the Regulators of Complement Activation Cluster Producing a Hybrid Complement Factor H/Complement Factor H–Related 3 Gene in Atypical Hemolytic Uremic Syndrome. Journal of the American Society of Nephrology 2016, 27(6), 1617-1624.
- Smith-Jackson K, Denton H, Cook K, Pickering MC, Cook TH, Marchbank KJ. A novel C3 gain of function mouse model of atypical haemolytic uraemic syndrome. In: 26th International Complement Workshop (XXVI ICW). 2016, Kanazawa, Japan: Elsevier GmbH - Urban und Fischer.
- Schmidt CQ, Harder M, Nichols E, Hebecker M, Anliker M, Höchsmann B, Simmet T, Csincsi ÁI, Uzonyi B, Pappworth IY, Ricklin D, Lambris JD, Schrezenmeier H, Józsi M, Marchbank KJ. Selectivity of C3-opsonin targeted complement inhibitors: a distinct advantage in the protection of erythrocytes from paroxysmal nocturnal hemoglobinuria patients . Immunobiology 2016, 221(4), 503-511.
- Phillips EH, Westwood JP, Brocklebank V, Wong EKS, Tellez JO, Marchbank KJ, McGuckin S, Gale DP, Connolly J, Goodship THJ, Kavanagh D, Scully MA. The role of ADAMTS-13 activity and complement mutational analysis in differentiating acute thrombotic microangiopathies. Journal of Thrombosis and Haemostasis 2016, 14(1), 175-185.
- Nichols E, Jones R, Watson R, Pepper CJ, Fegan C, Marchbank KJ. A CD21 low phenotype, with no evidence of autoantibodies to complement proteins, is consistent with a poor prognosis in CLL. Oncotarget 2015, 6(32), 32669-32680.
- Nichols E, Barbour TD, Pappworth IY, Wong EKS, Palmer J, Sheerin N, Pickering MC, Marchbank KJ. An extended mini-complement factor H molecule ameliorates experimental C3 glomerulopathy. Kidney International 2015, 88(6), 1314-1322.
- Watson R, Wearmouth E, McLoughlin A-C, Jackson A, Ward S, Bertram P, Bennaceur K, Barker CE, Pappworth IY, Kavanagh D, Lea SM, Atkinson JP, Goodship THJ, Marchbank KJ. Autoantibodies to CD59, CD55, CD46 or CD35 are not associated with atypical haemolytic uraemic syndrome (aHUS). Molecular Immunology 2015, 63(2), 287-296.
- Nichols EM, Barbour TD, Kerr H, Pappworth IY, Wong EKS, Palmer J, Sheerin NS, Herbert A, Barlow PN, Pickering MC, Marchbank KJ. FH1-5(18-20) ameliorates experimental C3 glomerulopathy; generation and testing of a murine version for further pre-clinical experiments. In: 15th European Meeting on Complement in Human Disease 2015. 2015, Uppsala, Sweden: Elsevier.
- Wong EKS, Marchbank K, Pappworth I, Walters R, Lomax-Browne H, Harris C, Morgan P, Pickering M, Goodship THJ, Malcomson R, Cook T, Johnson S, MPGN C3G Rare Dis Grp. The national study of membranoproliferative glomerulonephrtis and C3 glomerulopathy - characterisation of the paediatric cohort. In: 52nd ERA-EDTA Congress. 2015, London, UK: Oxford University Press.
- Blom AM, Volokhina EB, Fransson V, Stromberg P, Berghard L, Viktorelius M, Mollnes TE, Lopez-Trascasa M, van den Heuvel LP, Goodship TH, Marchbank KJ, Okroj M. A novel method for direct measurement of complement convertases activity in human serum. Clinical & Experimental Immunology 2014, 178(1), 142-153.
- Wong EKS, Anderson HE, Herbert AP, Challis RC, Brown P, Reis GS, Tellez JO, Strain L, Fluck N, Humphrey A, Macleod A, Richards A, Ahlert D, Santibanez-Koref M, Barlow PN, Marchbank KJ, Harris CL, Goodship THJ, Kavanagh D. Characterization of a Factor H Mutation That Perturbs the Alternative Pathway of Complement in a Family with Membranoproliferative GN. Journal of American Society of Nephrology 2014, 25(11), 2425-2433.
- Watson R, Lindner S, Bordereau P, Hunze EM, Tak F, Ngo S, Zipfel PF, Skerka C, Dragon-Durey MA, Marchbank KJ. Standardisation of the factor H autoantibody assay. Immunobiology 2014, 219(1), 9-16.
- Holmes LV, Strain L, Staniforth SJ, Moore I, Marchbank K, Kavanagh D, Goodship JA, Cordell HJ, Goodship THJ. Determining the Population Frequency of the CFHR3/CFHR1 Deletion at 1q32. PLoS ONE 2013, 8(4), e60352.
- Wilson V, Darlay R, Wong W, Wood KM, McFarlane J, Schejbel L, Schmidt IM, Harris CL, Tellez J, Hunze EM, Marchbank K, Goodship JA, Goodship THJ. Genotype/Phenotype Correlations in Complement Factor H Deficiency Arising From Uniparental Isodisomy. American Journal of Kidney Diseases 2013, 62(5), 978-983.
- Francis NJ, McNicholas B, Awan A, Waldron M, Reddan D, Sadlier D, Kavanagh D, Strain L, Marchbank KJ, Harris CL, Goodship THJ. A novel hybrid CFH/CFHR3 gene generated by a microhomology-mediated deletion in familial atypical hemolytic uremic syndrome. Blood 2012, 119(2), 591-601.
- Goodship THJ, Pappworth IY, Toth T, Denton M, Houlberg K, McCormick F, Warland D, Moore I, Hunze EM, Staniforth SJ, Hayes C, Cavalcante DP, Kavanagh D, Strain L, Herbert AP, Schmidt CQ, Barlow PN, Harris CL, Marchbank KJ. Factor H autoantibodies in membranoproliferative glomerulonephritis. Molecular Immunology 2012, 52(3-4), 200-206.
- Kavanagh D, Pappworth IY, Anderson H, Hayes CM, Moore I, Hunze EM, Bennaceur K, Roversi P, Lea S, Strain L, Ward R, Plant N, Nailescu C, Goodship TH, Marchbank KJ. Factor I Autoantibodies in Patients with Atypical Hemolytic Uremic Syndrome: Disease-Associated or an Epiphenomenon?. Clinical Journal of the American Society of Nephrology 2012, 7(3), 417-426.
- Brown JH, Tellez J, Wilson V, Mackie IJ, Scully M, Tredger MM, Moore I, McDougall NI, Strain L, Marchbank KJ, Sheerin NS, O'Grady J, Harris CL, Goodship THJ. Postpartum aHUS Secondary to a Genetic Abnormality in Factor H Acquired Through Liver Transplantation. American Journal of Transplantation 2012, 12(6), 1632-1636.
- Moore I, Strain L, Pappworth I, Kavanagh D, Barlow PN, Herbert AP, Schmidt CQ, Staniforth SJ, Holmes LV, Ward R, Morgan L, Goodship THJ, Marchbank KJ. Association of factor H autoantibodies with deletions of CFHR1, CFHR3, CFHR4, and with mutations in CFH, CFI, CD46, and C3 in patients with atypical hemolytic uremic syndrome. Blood 2010, 115(2), 379-387.
- Dhillon B, Wright AF, Tufail A, Pappworth I, Hayward C, Moore I, Strain L, Kavanagh D, Barlow PN, Herbert AP, Schmidt CQ, Armbrecht AM, Laude A, Deary IJ, Staniforth SJ, Holmes LV, Goodship THJ, Marchbank KJ. Complement Factor H Autoantibodies and Age-Related Macular Degeneration. Investigative Ophthalmology & Visual Science 2010, 51(11), 5858-5863.
- Depoil D, Fleire S, Treanor BL, Weber M, Harwood NE, Marchbank KL, Tybulewicz VLJ, Batista FD. CD19 is essential for B cell activation by promoting B cell receptor-antigen microcluster formation in response to membrane-bound ligand. Nature Immunology 2008, 9(1), 63-72.
- Twohig J, Kulik L, Haluszczak C, Reuter J, Rossbach A, Bull M, Holers VM, Marchbank KJ. Defective B cell ontogeny and immune response in human complement receptor 2 (CR2, CD21) transgenic mice is partially recovered in the absence of C3. Molecular Immunology 2007, 44(13), 3434-3444.
- Kulik L, Marchbank KJ, Lyubchenko T, Kuhn KA, Liubchenko GA, Haluszczak C, Gipson MG, Boackle SA, Holers VM. Intrinsic B cell hypo-responsiveness in mice prematurely expressing human CR2/CD21 during B cell development. European Journal of Immunology 2007, 37(3), 623-633.
- Birrell L, Kulik L, Morgan BP, Holers VM, Marchbank KJ. B Cells from Mice Prematurely Expressing Human Complement Receptor Type 2 are Unresponsive to T-Dependent Antigens. Journal of Immunology 2005, 174(11), 6974-6982.