Professor Claire Harris
Professor of Molecular Immunology
- Email: email@example.com
- Telephone: +44 (0) 191 208 5105
- Address: Institute of Cellular Medicine
3rd Floor Leech Building
Newcastle upon Tyne
Complement provides innate immune defence against infection and is an important driver of inflammation. However, inappropriate or uncontrolled activation of complement causes local and/or systemic inflammation, tissue damage and disease. I am interested in the mechanisms by which complement drives inflammatory disease, whether it be directly or as an amplifier of other triggers. Recent work includes functional characterization of complement protein variants/mutants associated with diseases such as age-related macular degeneration (AMD), atypical haemolytic uremic syndrome (aHUS) and C3 glomerulopathy (C3G). This work has led to the concept of the 'complotype' -the influence of complement genetic makeup on inflammation & infection (see ‘The complotype: dictating risk for inflammation and infection’. Trends in Immunology (2012), 33: 513). My current research is focussed on therapeutic approaches for modulation or inhibition of the complement cascade, particularly on strategies to target or ‘home’ therapy specifically to disease sites (see ‘An anti-complement agent that homes to the damaged brain and promotes recovery after traumatic brain injury in mice’. Proc Natl Acad Sci U S A (2015), 112:14319). I have a long-standing interest in complement biomarkers of disease (diagnostics, prognostics), including measurement of complement proteins and activation products, and detection and functional analysis of nephritic factors (autoantibodies which bind complement enzymes). These combined research foci provide insight into disease mechanisms which will be critical for design of effective anti-complement therapies and stratification of patients. A period of time spent as Head of Complement at GlaxoSmithKline in the ImmunoInflammation Therapy Area (2013-2016) provided invaluable insight into the process of target and indication validation and drug discovery (see ‘Complement, a target for therapy in inflammatory and degenerative diseases’. Nat Rev Drug Discov. 2015;14:857); I joined Newcastle University in 2016 to further my work in translational research and experimental medicine.
Area of expertise
- Innate immunity
- Drug discovery
- Feb 2017-present; Honorary Chair, Cardiff University
- August 2013-May 2016; Personal Chair, Institute of Infection & Immunity, School of Medicine, Cardiff University
- June 2013-April 2016; Complement Head, Director, Cytokine, Chemokine & Complement Discovery Performance Unit, ImmunoInflammation Therapy Area, GlaxoSmithKline, Stevenage, UK.
- August 2010-July 2013; Reader, School of Medicine, Cardiff University
- August 2003-July 2010; Senior Lecturer, School of Medicine, Cardiff University
- August 2002-August 2003; Lecturer, Department of Medical Biochemistry, University of Wales College of Medicine.
- 1985-1989: BSc Hons in Biochemistry; University of York
- 1989-1993: PhD; MRC Centre, University of Cambridge
- Complement therapeutics incorporating target validation, indication validation, proof-of-concept work; patient phenotyping & stratification.
- Structure/function relationships in complement activators and regulators with a particular interest in the mechanisms underlying complement dysregulation.
- Complement biomarkers (multiplexed assays for complement components and activation markers; nephritic factors).
- Complement and cancer, with a particular focus on the role of complement in promoting tumorigenesis.
- Complement and vaccination (GSK CASE studentship), exploring the way in which complement bactericidal assays are used to assess vaccine efficacy in clinical trials; determination of the best methods to predict vaccine efficacy using complement functional assays.
The Harris group is a key component of theNational Renal Complement Therapeutics Centre based at RVI (aHUS National Service) and other national/international Rare Disease Working Groups. We work in close collaboration with Dr Kevin Marchbank (ICM), Dr David Kavanagh (IGM), Prof Tim Goodship (IGM), Prof Neil Sheerin (ICM) and Dr Sally Johnson (Great North Children’s Hospital).
National Renal Complement Therapeutics Centre:
- Harris CL. Expanding horizons in complement drug discovery: challenges and emerging strategies. Seminars in Immunopathology 2018, 40(1), 125-140.
- Calippe B, Augustin S, Beguier F, Charles-Messance H, Poupel L, Conart J-B, Hu SJ, Lavalette S, Fauvet A, Rayes J, Levy O, Raoul W, Fitting C, Denefle T, Pickering MC, Harris C, Jorieux S, Sullivan PM, Sahel J-A, Karoyan P, Sapieha P, Guillonneau X, Gautier EL, Sennlaub F. Complement Factor H Inhibits CD47-Mediated Resolution of Inflammation. Immunity 2017, 46(2), 261-272.
- Loveless S, Neal JW, Howell OW, Harding KE, Sarkies P, Evans R, Bevan RJ, Hakobyan S, Harris CL, Robertson NP, Morgan BP. Tissue microarray methodology identifies complement pathway activation and dysregulation in progressive multiple sclerosis. Brain Pathology 2017, Epub ahead of print.
- 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.
- Hakobyan S, Harding K, Aiyaz M, Hye A, Dobson R, Baird A, Liu B, Harris CL, Lovestone S, Morgan BP. Complement Biomarkers as Predictors of Disease Progression in Alzheimer's Disease. Journal of Alzheimer's Disease 2016, 54(2), 707-716.
- Jones S, Humphries H, Gorringe A, Walters D, Morgans BP, Taylor S, Harris CL. Mechanisms responsible for differential bactericidal activities of human and rabbit complement for Neisseria meningitidis. In: 26th International Complement Workshop (XXVI ICW). 2016, Kanazawa, Japan: Elsevier GmbH - Urban und Fischer.
- Owen EP, Würzner R, Leisegang F, Rizkallah P, Whitelaw A, Simpson J, Thomas AD, Harris CL, Giles JL, Hellerud BC, Mollnes TE, Morgan BP, Potter PC, Orren A. A complement C5 gene mutation, c.754G>A:p.A252T, is common in the Western Cape, South Africa and found to be homozygous in seven percent of Black African meningococcal disease cases. Molecular Immunology 2015, 64(1), 170-176.
- Ruseva M, Ramaglia V, Morgan BP, Harris CL. An anticomplement agent that homes to the damaged brain and promotes recovery after traumatic brain injury in mice. Proceedings of the National Academy of Sciences of the United States of America 2015, 112(46), 14319-14324.
- Morgan BP, Harris CL. Complement, a target for therapy in inflammatory and degenerative diseases. Nature Reviews Drug Discovery 2015, 14, 857-877.
- Sei Y, Mizuno M, Suzuki Y, Imai M, Higashide K, Harris CL, Sakata F, Iguchi D, Fujiwara M, Kodera Y, Maruyama S, Matsuo S, Ito Y. Expression of membrane complement regulators, CD46, CD55 and CD59, in mesothelial cells of patients on peritoneal dialysis therapy. Molecular Immunology 2015, 65(2), 302-309.
- Giles JL, Choy E, Van Den Berg C, Morgan BP, Harris CL. Response to comment on "Functional Analysis of a Complement Polymorphism (rs17611) Associated with Rheumatoid Arthritis". Journal of Immunology 2015, 195(1), 4.
- MartínezBarricarte R, Heurich M, LópezPerrote A, Tortajada A, Pinto S, LópezTrascasa M, SánchezCorral P, Morgan BP, Llorca O, Harris CL, RodríguezdeCórdoba S. The molecular and structural bases for the association of complement C3 mutations with atypical hemolytic uremic syndrome. Molecular Immunology 2015, 66(2), 263-273.
- 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.
- PaixãoCavalcante D, Torreira E, Lindorfer MA, RodriguezdeCordoba S, Morgan BP, Taylor RP, Llorca O, Harris CL. A humanized antibody that regulates the alternative pathway convertase: potential for therapy of renal disease associated with nephritic factors. Journal of Immunology 2014, 192(10), 4844-4851.
- 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.
- Ingram G, Loveless S, Howell OW, Hakobyan S, Dancey B, Harris CL, Robertson NP, Neal JW, Morgan BP. Complement activation in multiple sclerosis plaques: an immunohistochemical analysis. Acta Neuropathologica Communications 2014, 2, 53.
- Tortajada A, Yébenes H, Abarrategui-Garrido C, Anter J, García-Fernández JM, Martínez-Barricarte R, Alba-Dominguez M, Malik TH, Bedoya R, Pérez RC, Trascasa ML, Pickering MC, Harris CL, Sánchez-Corral P, Llorca O, Rodríguez-de-Córdoba S. C3 glomerulopathy-associated CFHR1 mutation alters FHR oligomerization and complement regulation. J Clin Invest 2013, 123(6), 2434-46.
- Goicoechea-de-Jorge E, Caesar JJ, Malik TH, Patel M, Colledge M, Johnson S, Hakobyan S, Morgan BP, Harris CL, Pickering MC, Lea SM. Dimerization of complement factor H-related proteins modulates complement activation in vivo. Proc Natl Acad Sci U S A 2013, 110(12), 4685-90.
- 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.
- RodriguezdeCordoba SR, Tortajada A, Harris CL, Morgan BP. Complement dysregulation and disease: From genes and proteins to diagnostics and drugs. Immunobiology 2012, 217(11), 1034-46. In Preparation.
- 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.
- Paixão-Cavalcante D, López-Trascasa M, Skattum L, Giclas PC, Goodship TH, Rodríguez de Córdoba S, Truedsson L, Morgan BP, Harris CL. Sensitive and specific assays for C3 nephritic factors clarify mechanisms underlying complement dysregulation. Kidney International 2012, 82(10), 1084-1092.
- Heurich M, MartínezBarricarte R, Francis NJ, Roberts DL, RodríguezdeCórdoba S, Morgan BP, Harris CL. Common polymorphisms in C3, factor B, and factor H collaborate to determine systemic complement activity and disease risk. Proc Natl Acad Sci U S A 2011, 108(21), 8761-6.
- Pechtl IC, Kavanagh D, McIntosh N, Harris CL, Barlow PN. Disease-associated N-terminal complement factor H mutations perturb cofactor and decay-accelerating activities. Journal of Biological Chemistry 2011, 286(13), 11082-11090.
- Roversi P, Johnson S, Caesar JJ, McLean F, Leath KJ, Tsiftsoglou SA, Morgan BP, Harris CL, Sim RB, Lea SM. Structural basis for complement factor I control and its disease-associated sequence polymorphisms. Proc Natl Acad Sci U S A 2011, 108(31), 12839-44.
- Alcorlo M, MartínezBarricarte R, Fernandez FJ, RodríguezGallego C, Round A, Vega MC, Harris CL, RodríguezdeCordoba S, Llorca O. Unique structure of iC3b resolved at a resolution of 24 A by 3D-electron microscopy. Proc Natl Acad Sci U S A 2011, 108(32), 13236-40.
- MartínezBarricarte R, Heurich M, ValdesCañedo F, VazquezMartul E, Torreira E, Montes T, Tortajada A, Pinto S, LopezTrascasa M, Morgan BP, Llorca O, Harris CL, RodríguezdeCórdoba S. Human C3 mutation reveals a mechanism of dense deposit disease pathogenesis and provides insights into complement activation and regulation. J Clin Invest 2010, 120(10), 3702-3712.
- Tortajada A, Montes T, MartinezBarricarte R, Morgan BP, Harris CL, RodríguezdeCórdoba S. Complement factor H Val62Ile polymorphism increases affinity for C3b binding and enhances cofactor activity. Human Molecular Genetics 2009, 18(18), 3452-61. In Preparation.
- Montes T, Tortajada A, Morgan BP, RodríguezdeCórdoba S, Harris CL. Functional basis of protection against age-related macular degeneration conferred by a common polymorphism in complement factor B. Proc Natl Acad Sci U S A 2009, 106(11), 4366-71.
- Hakobyan S, Harris CL, Tortajada A, GoicocheadeJorge E, GarcíaLayana A, FernándezRobredo P, RodríguezdeCórdoba S, Morgan BP. Measurement of factor H variants in plasma using variant-specific monoclonal antibodies: application to assessing risk of age-related macular degeneration. Invest Ophthalmol Vis Sci 2008, 49(5), 1983-90.
- Hepburn NJ, ChamberlainBanoub JL, Williams AS, Morgan BP, Harris CL. Prevention of experimental autoimmune myasthenia gravis by rat Crry-Ig: A model agent for long-term complement inhibition in vivo. Mol Immunol 2008, 45(2), 395-405.
- Harris C, Pettigrew DM, Lea SM, Morgan BP. Decay accelerating factor must bind both components of the complement alternative pathway C3 convertase to mediate efficient decay. J Immunol 2007, 178(1), 352-9.
- GoicoecheadeJorge E, Harris CL, EsparzaGordillo J, Carreras L, AllerArranz E, AbarrateguiGarrido C, LópezTrascasa M, SánchezCorral P, Morgan BP, RodríguezdeCórdoba S. Gain-of-function mutations in complement factor B are associated with atypical hemolytic uremic syndrome. Proc Natl Acad Sci U S A 2007, 104(1), 240-5.
- Hepburn NJ, Williams AS, Nunn MA, ChamberlainBanoub JC, Hamer J, Morgan BP, Harris CL. In vivo characterization and therapeutic efficacy of a C5-specific inhibitor from the soft tick Ornithodoros moubata. J Biol Chem 2007, 282(11), 8292-9.
- Morgan BP, Marchbank KJ, Longhi MP, Harris CL, Gallimore AM. Complement: central to innate immunity and bridging to adaptive responses. Immunology Letters 2005, 97(2), 171-179.
- Morgan BP, Harris CL. DUPLICATE REFERENCE. 0.