Dr Claire Harris
- harriscl@cardiff.ac.uk
- Henry Wellcome Building
- Sylwebydd y cyfryngau
Trosolwg
There are two primary research areas in my research group. The first is to interrogate structure/function relationships in the complement system at the biochemical level in order to further our understanding of the mechanisms underlying complement dysregulation and disease; and the second is to utilise the knowledge obtained to design improved and targeted therapies for diseases driven by complement.
I have developed novel techniques to understand how minor changes, such as common polymorphisms (genetic variations) in complement proteins, can affect function; these findings have opened the door to exciting new research in the field of complement in human disease.
Key techniques in the group include: surface plasmon resonance, protein purification (affinity and classical chromatography), immunoassay development, monoclonal antibody/hybridoma production, protein engineering and expression.
Cyhoeddiadau
2018
- Zelek, W. M., Harris, C. L. and Morgan, B. P. 2018. Extracting the barbs from complement assays: Identification and optimisation of a safe substitute for traditional buffers. Immunobiology 223(12), pp. 744-749. (10.1016/j.imbio.2018.07.016)
- Loveless, S. et al. 2018. Tissue microarray methodology identifies complement pathway activation and dysregulation in progressive multiple sclerosis. Brain Pathology 28(4), pp. 507-520. (10.1111/bpa.12546)
2017
- Calippe, B. et al. 2017. Complement factor H inhibits CD47-Mediated resolution of inflammation. Immunity 46(2), pp. 261-272. (10.1016/j.immuni.2017.01.006)
2016
- Hakobyan, S. et al. 2016. Complement biomarkers as predictors of disease progression in Alzheimer's disease. Journal of Alzheimer's Disease 54(2), pp. 707-716. (10.3233/JAD-160420)
- Challis, R. C. et al. 2016. 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 27(6), pp. 1617-1624. (10.1681/ASN.2015010100)
2015
- Ruseva, M. M., Ramaglia, V., Morgan, B. P. and Harris, C. L. 2015. 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 112(46), pp. 14319-14324. (10.1073/pnas.1513698112)
- Martínez-Barricarte, R. et al. 2015. The molecular and structural bases for the association of complement C3 mutations with atypical hemolytic uremic syndrome. Molecular Immunology 66(2), pp. 263-273. (10.1016/j.molimm.2015.03.248)
- Giles, J. L., Choy, E., van den Berg, C., Morgan, B. P. and Harris, C. L. 2015. Response to comment on 'Functional analysis of a complement polymorphism (rs17611) associated with rheumatoid arthritis'. Journal of Immunology 195(1), pp. 4-4. (10.4049/jimmunol.1500968)
- Sei, Y. et al. 2015. Expression of membrane complement regulators, CD46, CD55 and CD59, in mesothelial cells of patients on peritoneal dialysis therapy. Molecular Immunology 65(2), pp. 302-309. (10.1016/j.molimm.2015.02.005)
- Owen, E. P. et al. 2015. 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 64(1), pp. 170-176. (10.1016/j.molimm.2014.11.010)
- Giles, J., Choy, E. H. S., Van Den Berg, C., Morgan, B. P. and Harris, C. L. 2015. Functional analysis of a complement polymorphism (rs17611) associated with rheumatoid arthritis. The Journal of Immunology 194(7), pp. 3029-3034. (10.4049/jimmunol.1402956)
2014
- Giles, J. L., Choy, E., van den Berg, C., Morgan, B. P. and Harris, C. L. 2014. Functional analysis of a complement polymorphism (rs17611) associated with Rheumatoid Arthritis. Immunology 143(s2), pp. 181-182. (10.1111/imm.12407)
- Wong, E. K. et al. 2014. Characterization of a factor H mutation that perturbs the alternative pathway of complement in a family with membranoproliferative GN. Journal of the American Society of Nephrology 25(11), pp. 2425-2433. (10.1681/ASN.2013070732)
- Paixao-Cavalcante, D. et al. 2014. A humanized antibody that regulates the alternative pathway convertase: potential for therapy of renal disease associated with nephritic factors. The Journal of Immunology 192(10), pp. 4844-4851. (10.4049/jimmunol.1303131)
- Ingram, G. et al. 2014. Complement activation in multiple sclerosis plaques: an immunohistochemical analysis. Acta Neuropathologica Communications 2, article number: 53. (10.1186/2051-5960-2-53)
2013
- Wilson, V. et al. 2013. Genotype/Phenotype correlations in complement factor H deficiency arising from uniparental isodisomy. American Journal of Kidney Diseases 62(5), pp. 978-983. (10.1053/j.ajkd.2013.05.020)
- Pickering, M. C. et al. 2013. C3 glomerulopathy: consensus report. Kidney International 84(6), pp. 1079-1089. (10.1038/ki.2013.377)
- Tortajada, A. et al. 2013. C3 glomerulopathy-associated CFHR1 mutation alters FHR oligomerization and complement regulation. The Journal of Clinical Investigation 123(6), pp. 2434-2446. (10.1172/JCI68280)
- Gustafsson, M. et al. 2013. Factor H Binds to the hypervariable region of many streptococcus pyogenes M proteins but does not promote phagocytosis resistance or acute virulence. PLoS Pathogens 9(4), article number: e1003323. (10.1371/journal.ppat.1003323)
- Goicoechea de Jorge, E. et al. 2013. Dimerization of complement factor H-related proteins modulates complement activation in vivo. Proceedings of the National Academy of Sciences of the United States of America 110(12), pp. 4685-4690. (10.1073/pnas.1219260110)
- Adriani, K. S. et al. 2013. Common polymorphisms in the complement system and susceptiblity to bacterial meningitis. Journal of Infection 66(3), pp. 255-262. (10.1016/j.jinf.2012.10.008)
2012
- Paixao Cavalcante, D. et al. 2012. Sensitive and specific assays for C3 nephritic factors clarify mechanisms underlying complement dysregulation. Kidney International 82(10), pp. 1084-1092. (10.1038/ki.2012.250)
- Harris, C. L., Heurich, M., Rodriguez de Cordoba, S. and Morgan, B. P. 2012. The complotype: dictating risk for inflammation and infection. Trends in Immunology 33(10), pp. 513-521. (10.1016/j.it.2012.06.001)
- Goodship, T. H. et al. 2012. Factor H autoantibodies in membranoproliferative glomerulonephritis. Molecular Immunology 52(3-4), pp. 200-206. (10.1016/j.molimm.2012.05.009)
- Ingram, G. et al. 2012. Systemic complement profiling in multiple sclerosis as a biomarker of disease state. Multiple Sclerosis Journal 18(10), pp. 1401-1411. (10.1177/1352458512438238)
- Kempshall, E., Thebault, S., Morgan, B. P., Harris, C. L. and Gallimore, A. M. 2012. Complement-induced protection: an explanation for the limitations of cell-based tumour immunotherapies. Immunology and Cell Biology 90(9), pp. 869-871. (10.1038/icb.2012.30)
- Brown, J. H. et al. 2012. Postpartum aHUS secondary to a genetic abnormality in factor H acquired through liver transplantation. American Journal of Transplantation 12(6), pp. 1632-1636. (10.1111/j.1600-6143.2012.03991.x)
- Mizuno, M. et al. 2012. Membrane complement regulators protect against fibrin exudation increases in a severe peritoneal inflammation model in rats. American Journal of Physiology-Renal Physiology 302(10), pp. F1245-F1251. (10.1152/ajprenal.00652.2011)
- Francis, N. et al. 2012. A novel hybrid CFH/CFHR3 gene generated by a microhomology-mediated deletion in familial atypical hemolytic uremic syndrome. Blood 119(2), pp. 591-601. (10.1182/blood-2011-03-339903)
- Gibson, J. et al. 2012. Variation in complement component C1 inhibitor in age-related macular degeneration. Immunobiology 217(2), pp. 251-255. (10.1016/j.imbio.2011.07.015)
2011
- de Córdoba, S. R., Harris, C. L., Morgan, B. P. and Llorca, O. 2011. Lessons from functional and structural analyses of disease-associated genetic variants in the complement alternative pathway. Biochimica et Biophysica Acta - Molecular Basis of Disease 1812(1), pp. 12-22. (10.1016/j.bbadis.2010.09.002)
- Heurich, M., Martinez-Barricarte, R., Francis, N., Roberts, D. L., Rodriguez de Cordoba, S., Morgan, B. P. and Harris, C. L. 2011. Common polymorphisms in C3, factor B, and factor H collaborate to determine systemic complement activity and disease risk. Proceedings of the National Academy of Sciences of the United States of America 108(21), pp. 8761-8766. (10.1073/pnas.1019338108)
- Roversi, P. et al. 2011. Structural basis for complement factor I control and its disease-associated sequence polymorphisms. Proceedings of the National Academy of Sciences of the United States of America 108(31), pp. 12839-12844. (10.1073/pnas.1102167108)
- Alcorlo, M. et al. 2011. Unique structure of iC3b resolved at a resolution of 24 Å by 3D-electron microscopy. Proceedings of the National Academy of Sciences of the United States of America 108(32), pp. 13236-13240. (10.1073/pnas.1106746108)
- Alcorlo, M. et al. 2011. Correction for Alcorlo et al., Unique structure of iC3b resolved at a resolution of 24 A by 3D-electron microscopy [Correction]. Proceedings of the National Academy of Sciences 108(39), pp. 16481. (10.1073/pnas.1112875108)
- Pechtl, I. C., Kavanagh, D., Mcintosh, N., Harris, C. L. and Barlow, P. N. 2011. Disease-associated N-terminal Complement Factor H Mutations Perturb Cofactor and Decay-accelerating Activities. Journal of Biological Chemistry 286(13), pp. 11082-11090. (10.1074/jbc.M110.211839)
- Smith, R. J. H., Harris, C. L. and Pickering, M. C. 2011. Dense deposit disease. Molecular Immunology 48(14), pp. 1604-1610. (10.1016/j.molimm.2011.04.005)
- Roversi, P. et al. 2011. Structures of the rat complement regulator CrrY. Acta Crystallographica Section F: Structural Biology and Crystallization Communications 67(7), pp. 739-743. (10.1107/S1744309111016551)
2010
- Martínez-Barricarte, R. et al. 2010. Human C3 mutation reveals a mechanism of dense deposit disease pathogenesis and provides insights into complement activation and regulation. Journal of Clinical Investigation 120(10), pp. 3702-3712. (10.1172/JCI43343)
- Ingram, G. et al. 2010. Complement regulator factor H as a serum biomarker of multiple sclerosis disease state. Brain 133(6), pp. 1602-1611. (10.1093/brain/awq085)
- Manickam, B., Jha, P., Hepburn, N. J., Morgan, B. P., Harris, C. L., Bora, P. S. and Bora, N. S. 2010. Suppression of complement activation by recombinant Crry inhibits experimental autoimmune anterior uveitis (EAAU). Molecular Immunology 48(1-3), pp. 231-239. (10.1016/j.molimm.2010.08.006)
- Hakobyan, S., Tortajada, A., Harris, C. L., de Córdoba, S. R. and Morgan, B. P. 2010. Variant-specific quantification of factor H in plasma identifies null alleles associated with atypical hemolytic uremic syndrome. Kidney International 78(8), pp. 782-788. (10.1038/ki.2010.275)
2009
- Tortajada, A., Montes, T., Martinez-Barricarte, R., Morgan, B. P., Harris, C. L. and de Cordoba, S. R. 2009. The disease-protective complement factor H allotypic variant Ile62 shows increased binding affinity for C3b and enhanced cofactor activity. Human Molecular Genetics 18(18), pp. 3452-3461. (10.1093/hmg/ddp289)
- Hughes, T. R., Ross, K. S., Cowan, G. J. M., Baalasubramanian, S., Harris, C. L., Mitchell, T. J. and Morgan, B. P. 2009. Identification of the high affinity binding site in the Streptococcus intermedius toxin intermedilysin for its membrane receptor, the human complement regulator CD59. Molecular Immunology 46(7), pp. 1561-1567. (10.1016/j.molimm.2009.01.003)
- Montes, T., Tortajada, A., Morgan, B. P., Rodriguez de Cordoba, S. and Harris, C. L. 2009. Functional basis of protection against age-related macular degeneration conferred by a common polymorphism in complement factor B. Proceedings of the National Academy of Sciences 106(11), pp. 4366-4371. (10.1073/pnas.0812584106)
- Ruseva, M. M. et al. 2009. Crry deficiency in complement sufficient mice: C3 consumption occurs without associated renal injury. Molecular Immunology 46(5), pp. 803-811. (10.1016/j.molimm.2008.09.003)
- Kolev, M., Ruseva, M. M., Harris, C. L., Morgan, B. P. and Donev, R. M. 2009. Implication of complement system and its regulators in Alzheimer's Disease. Current Neuropharmacology 7(1), pp. 1-8.
- Kolev, M., Tediose, T., Baalasubramanian, S., Harris, C. L., Thome, J., Morgan, B. P. and Donev, R. M. 2009. Upregulating CD59: a new strategy for protection of neurons from complement-mediated degeneration. The Pharmacogenomics Journal 10(1), pp. 12-19. (10.1038/tpj.2009.52)
- Mizuno, M. et al. 2009. Zymosan, but not lipopolysaccharide, triggers severe and progressive peritoneal injury accompanied by complement activation in a rat peritonitis model. The Journal of Immunology 183(2), pp. 1403-1412. (10.4049/jimmunol.0804245)
2008
- Hakobyan, S. et al. 2008. Complement factor H binds to denatured rather than to native pentameric C-reactive protein. Journal of Biological Chemistry 283(45), pp. 30451-30460. (10.1074/jbc.M803648200)
- Hepburn, N. J., Ruseva, M. M., Harris, C. L. and Morgan, B. P. 2008. Complement, roles in renal disease and modulation for therapy. Clinical Nephrology 70(5), pp. 357-376.
- Hepburn, N. J., Chamberlain-Banoub, J. L., Williams, A. S., Morgan, B. P. and Harris, C. L. 2008. Prevention of experimental autoimmune myasthenia gravis by rat Crry-Ig: a model agent for long-term complement inhibition in vivo. Molecular Immunology 45(2), pp. 395-405. (10.1016/j.molimm.2007.06.144)
- Hakobyan, S. et al. 2008. Measurement of factor H variants in plasma using variant-specific monoclonal antibodies: application to assessing risk of age-related macular degeneration. Investigative Ophthalmology and Visual Science 49(5), pp. 1983-1990. (10.1167/iovs.07-1523)
2007
- Hepburn, N. J., Williams, A. S., Morgan, B. P. and Harris, C. L. 2007. In Vivo Characterization and Therapeutic Efficacy of a C5-specific Inhibitor from the Soft Tick Ornithodoros moubata. J Biol Chem 282, pp. 8292-8299. (10.1074/jbc.M609858200)
- Harris, C. L., Cordoba, S. R. d., Jorge, E. G. d. and Morgan, B. P. 2007. Gain-of-function mutations in complement factor B are associated with atypical hemolytic uremic syndrome. Proceedings of the National Academy of Sciences 104(1), pp. 240-5. (10.1073/pnas.0603420103)
- Harris, C. L., Morgan, B. P., Pettigrew, D. and Lea, S. 2007. Decay-accelerating factor must bind both components of the complement alternative pathway c3 convertase to mediate efficient decay. Journal of Immunology 178, pp. 352-359.
- Hepburn, N. J., Williams, A. S., Chamberlain, J. C., Hamer, J., Nunn, M. A., Morgan, B. P. and Harris, C. L. 2007. In vivo characterisation and therapeutic efficacy of a C5-specific inhibitor [Abstract]. Molecular Immunology 44(1-3), pp. 183-183. (10.1016/j.molimm.2006.07.087)
- Mizuno, M., Donev, R. M., Harris, C. L. and Morgan, B. P. 2007. CD55 in rat male reproductive tissue: Differential expression in testis and expression of a unique truncated isoform on spermatozoa. Molecular Immunology 44(7), pp. 1613-1622. (10.1016/j.molimm.2006.08.018)
2005
- Harris, C. L., Morgan, B. P., Lea, S. M. and Abbott, R. J. 2005. Molecular dissection of interactions between components of the alternative pathway of complement and decay accelerating factor (CD55). Journal of Biological Chemistry 280(4), pp. 2569-78. (10.1074/jbc.M410179200)
2004
- Baalasubramanian, S., Harris, C. L., Donev, R. M., Mizuno, M., Omidvar, N., Song, W. and Morgan, B. P. 2004. CD59a is the primary regulator of membrane attack complex assembly in the mouse. Journal of Immunology 173, pp. 3684-3692.
- Harris, C. L. and Morgan, B. 2004. The many faces of the membrane regulators of complement. In: Szebeni, J. ed. The Complement System: Novel Roles in Health and Disease. Boston: Kluwer, pp. 129-166.
- Sivasankar, B., Mizuno, M., Donev, R. M., Omidvar, N., Harris, C. L., Song, W. C. and Morgan, B. P. 2004. CD59b is expressed at low level on mouse erythrocytes and has a negligible protective role in the presence of CD59a. Molecular Immunology 41(2-3), pp. 307-308. (10.1016/j.molimm.2004.03.002)
2003
- Williams, A. S., Fraser, D. A., Harris, C. L. and Mizuno, M. 2003. Generation of a recombinant, membrane-targeted form of the complement regulator CD59: activity in vitro and in vivo. The Journal of Biological Chemistry 278(49), pp. 48921-48927. (10.1074/jbc.M302598200)
- Harris, C. L., Hughes, C. E., Williams, A. S., Goodfellow, I., Evans, D. J., Caterson, B. and Morgan, B. P. 2003. Generation of anti-complement 'prodrugs': cleavable reagents for specific delivery of complement regulators to disease sites. The Journal of Biological Chemistry 278(38), pp. 36068-36076. (10.1074/jbc.M306351200)
- Clayton, A., Harris, C. L., Morgan, B. P. and Mason, M. D. 2003. Antigen-presenting cell exosomes are protected from complement-mediated lysis by expression of CD55 and CD59. European Journal of Immunology 33(2), pp. 522-31. (10.1002/immu.200310028)
2001
- Labeta, M. O., Nores, J. E. R., Vigar, M. . A. and Harris, C. L. 2001. The lipopolysaccharide co-receptor CD14 is present and functional in seminal plasma and expressed on spermatozoa. Immunology 104(3), pp. 317-23. (10.1046/j.1365-2567.2001.01312.x)
2000
- Harris, C. L. 2000. Functional assays for complement regulators. In: Morgan, B. P. ed. Complement Methods and Protocols. Methods in Molecular Biology Totowa, NJ: Humana Press, pp. 83-103.
My current research interrogates structure/function relationships in complement proteins to further understanding of the mechanisms underlying complement dysregulation and disease.
I have developed novel techniques to decipher how common polymorphisms in complement proteins affect function. With collaborators, I was the first to describe gain-of-function mutations in complement proteins which trigger renal disease (PNAS, 2007; JCI, 2010), and to define functional mechanisms behind common polymorphisms associated with age-related macular degeneration (AMD), and other diseases (PNAS 2009, HMG 2009, PNAS 2011).
I have described how the ‘complotype’ (the pattern of complement variants inherited by an individual) acts as a disease ‘hit’ with potential to predispose to chronic inflammatory disease or alter susceptibility to infection (Trends Immunol 2012). I am now applying these concepts to patient cohorts to understand relevance for patient care.
My interest in complement dysregulation includes mechanisms of dysregulation triggered by anti-complement autoantibodies; I am translating novel assays for these autoantibodies to the clinical immunology laboratory. I have a long-standing interest in design, engineering of anti-complement therapeutics and testing of these agents in animal models, a research theme which is strengthened by my focus on disease mechanisms.