Professor Matthew C Pickering

 

I am a Wellcome Trust Senior Fellow in Clinical Science leading a research program on the role of complement regulation in health and disease, specifically the relationship between uncontrolled complement activation and renal disease.

I am an Honorary Consultant Rheumatologist at Imperial College Academic Health Sciences Centre. My clinical interests include systemic lupus erythematosus and hereditary and acquired complement deficiency.

Basic Research

The research studies focused initially on one of the major regulatory proteins of the complement system, a molecule termed complement factor H (CFH). Mutations in CFH had been linked to two distinct human kidney disorders. One is characterised by complement-mediated inflammation (glomerulonephritis) and another by complement-mediated thrombosis (thrombotic microangiopathy). Utilising knock-out and transgenic mice strategies we have been able to define the molecular pathogenesis of these two kidney disorders. With respect to the glomerulonephritis, uncontrolled activation of the central component of the complement cascade (an abundant circulating protein termed C3) can trigger the development of glomerulonephritis (weblink). Subsequent insights from these in vivo models showed that activation of a complement protein distal to C3 (termed C5) contributes to glomerulonephritis (weblink), that specific fragments of C3 initiate the renal injury (weblink) and that the accumulation of these fragments in the kidney can be reversed by administration of CFH (weblink). With respect to renal thrombosis, the experiments have demonstrated that the condition develops as a consequence of defective targeting of CFH to renal endothelium (weblink) and that the thrombosis is critically dependent on C5 activation.

 

 

 

 

Clinical Research

I am interested in characterising complement deficiency states and in identifying novel complement susceptibility factors in renal disease. We have characterised the genetic basis and clinical course of hereditary C1q deficiency, including a novel case of combined C1q and C8 deficiency (weblink). Recently, together with Patrick Maxwell at UCL and Santiago Rodriguez de Cordoba (Centro de Investigaciones Biológicas, Madrid, weblink), we identified and characterised a mutation in a protein related to CFH (termed CFHR5) in Cypriot individuals with inherited glomerulonephritis (in press). For questions related to complement investigations please email matthew.pickering@imperial.ac.uk

 

 

 

 

  

 

 

  

SELECTED KEY PUBLICATIONS 

Research papers:

Human CFH rapidly reverses renal complement deposition in factor H-deficient mice. F Fakhouri, E Goicoechea de Jorge, F Brune, P Azam, HT Cook, MC Pickering. Kidney International 2010 weblink

Complement Factor H-Related protein 5 (CFHR5) Nephropathy: an endemic cause of renal disease in Cyprus. DP Gale, E Goicoechea de Jorge, HT Cook, R Martinez-Barricarte, A Hadjisavvas, AG McLean, CD Pusey, A Pierides, K Kyriacou, Y Athanasiou, K Voskarides, C Deltas, A Palmer, V Frémeaux-Bacchi, S Rodriguez de Cordoba, PH Maxwell, MC Pickering. Lancet 2010 [in press].

Paixão-Cavalcante D, Hanson S, Botto M, Cook HT, Pickering MC. Factor H facilitates the clearance of GBM bound iC3b by controlling C3 activation in fluid phase. Mol Immunol. 2009; 46:1942-50. weblink

Rose KL, Paixao-Cavalcante D, Fish J, Manderson AP, Malik TH, Bygrave AE, Lin T, Sacks SH, Walport MJ, Cook HT, Botto M, Pickering MC. Factor I is required for the development of membranoproliferative glomerulonephritis in factor H-deficient mice. J Clin Invest. 2008; 118:608-618. weblink

Pickering MC, Warren J, Rose KL, Carlucci F, Wang Y, Walport MJ, Cook HT, Botto M. Prevention of C5 activation ameliorates spontaneous and experimental glomerulonephritis in factor H-deficient mice. Proc Natl Acad Sci U S A. 2006; 103:9649-54. weblink

Pickering MC, Goicoechea de Jorge E, Martinez-Barricarte R, Recalde S, Garcia-Layana A, Rose, KL, Moss J, Walport MJ, Cook HT, Rodriguez de Cordoba S, Botto M. Spontaneous haemolytic uraemic syndrome triggered by complement factor H lacking surface recognition domains. J. Exp. Med. 2007; 204:1249-56. weblink

Pickering MC, Cook HT, Warren J, Bygrave AE, Moss J, Walport MJ, Botto M. Uncontrolled C3 activation causes membranoproliferative glomerulonephritis in mice deficient in complement factor H. Nature Genetics 2002; 31:424-8. weblink

Review articles:

Botto M, Kirschfink M, Macor P, Pickering MC, Würzner R, Tedesco F. Complement in human diseases: Lessons from complement deficiencies. Mol Immunol. 2009; 46:2774-83 weblink

Pickering MC, Cook HT. Translational mini-review series on complement factor H: renal diseases associated with complement factor H: novel insights from humans and animals. Clin Exp Immunol. 2008; 151: 210-30. weblink