Professor Marina Botto

 

Marina Botto FMedSci is the Director of the Centre for Complement and Inflammation Research (CCIR) and Professor of Rheumatology at the Imperial College London. She is also a Consultant Rheumatologist at Imperial Academic Health Science Centre, Hammersmith Campus.

The focus of my research programme is to understand how complement deficiency contributes to the autoimmune disease, systemic lupus erythematosus (SLE). We are particularly interested in understanding the consequences of inherited complement deficiencies in humans and the role(s) that the complement system plays in the clearance of dying cells as well as immune complexes. Using in vivo models, genetic and cellular approaches and experimental models of inflammation we have demonstrated that: i) inherited defects in the pathways for clearance of cellular debris and immune complexes predispose to the development of SLE; ii) there is a link between spontaneous autoimmunity and abnormalities of the physiological clearance of apoptotic cells in humans with complement deficiency; iii) the complement system modulates the adaptive immune system; iv) autoimmunity varies according to the genetic background of the model used and identified lupus susceptibility loci. We currently aim to delineate the contribution of complement system in the induction and resolution of inflammation and to define the mechanisms by which the complement system regulates the tolerance to self-antigens.

 

SELECTED KEY PUBLICATIONS

Mice lacking C1q or C3 show accelerated rejection of minor H disparate skin grafts and resistance to induction of tolerance. Baruah P, Simpson E, Dumitriu IE, Derbyshire K, Coe D, Addey C, Dyson J, Chai JG, Cook T, Scott D, Botto M. Eur J Immunol. 40(6):1758-1767, 2010

Immunoglobulin M is Required for Protection Against Atherosclerosis in Low-Density Lipoprotein Receptor-Deficient Mice. Myles J Lewis, Talat H Malik, Michael R Ehrenstein, Joseph J Boyle, Marina Botto, and Dorian O Haskard. Circulation 120(5):417-26, 2009

C1q enhances IFN-{gamma} production by antigen specific T cells via the CD40 co-stimulatory pathway on dendritic cells. Baruah P, Dumitriu IE, Malik TH, Cook HT, Dyson J, Scott D, Simpson E, Botto M. Blood 113(15):3485-93, 2009

Regulation of B cell tolerance by 129-derived chromosome 1 loci in C57BL/6 mice. Fossati-Jimack L, Cortes-Hernandez J, Norsworthy PJ, Cook HT, Walport MJ, Botto M. Arthritis Rheum. 58(7):2131-2141, 2008

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

Prevention of C5 activation ameliorates MPGN and heterologous nephritis in factor H-deficient mice. Pickering MC, Warren J, Rose KL, Carlucci F, Wang Y, Walport MJ, Cook HT and Botto M. Proc. Natl. Acad. Sci. USA 103:9649-9654, 2006

Spontaneous autoimmunity in 129 and C57BL/6 mice-implications for autoimmunity described in gene-targeted mice. A.E. Bygrave, K.L. Rose, J. Cortes-Hernandez, J. Warren, R.J. Rigby, H.T. Cook, M.J. Walport, T.J. Vyse, M. Botto. PLoS Biol. 2:1081-1090, 2004

The classical pathway is the dominant complement pathway required for innate immunity to Streptococcus pneumoniae infection in mice. JS Brown, T Hussell, S Gilliland, DW Holden, JC Paton, MR Ehrenstein, MJ Walport, M Botto. Proc. Natl. Acad. Sci. USA 99: 16969-16974, 2002

A hierarchical role for classical pathway complement proteins in the clearance of apoptotic cells in vivo. Taylor PR., Carugati A, Fadok VA, Cook HT, Andrews M, Carroll MC, Savill JS, Henson P, Botto M, Walport MJ. J. Exp Med 192, 359-366, 2000

Homozygous C1q deficiency causes glomerulonephritis associated with multiple apoptotic bodies. M. Botto, C Dell’Agnola, AE Bygrave, M Thompson, HT Cook, F Petry, M Loos, PP Pandolfi, MJ Walport. Nature Genetics 19:56-59, 1998