Research
Genetic and functional mechanisms of primary immune deficiency and autoimmunity
We are searching for genes in the human genome that carry sequence variants, which are involved in resistance to infection and predispose to infectious diseases. Discovery of such genes can open new biological pathways and suggest new targets for intervention. We use methods of human genetics, including genome-wide association studies (GWAS) and exome sequencing, in vitro models of infection and methods of molecular biology to understand underlying biological mechanisms.
Publications
Burns SO, Zenner HL, Plagnol V, Curtis J, Mok K, Eisenhut M, Kumararatne D, Döffinger R, Thrasher AJ, Nejentsev S. LRBA gene deletion in a patient presenting with autoimmunity without hypogammaglobulinemia. J Allergy Clin Immunol. 2012 Dec;130(6):1428-32.
Plagnol V, Curtis J, Epstein M, Mok KY, Stebbings E, Grigoriadou S, Wood NW, Hambleton S, Burns SO, Thrasher AJ, Kumararatne D, Döffinger R, Nejentsev S. A robust model for read count data in exome sequencing experiments and implications for copy number variant calling. Bioinformatics. 2012 Nov 1;28(21):2747-54
Lim MT, Jeyarajah K, Jones P, Pandya H, Döffinger R, Kumararatne D, Browning MJ, Gaillard EA. Specific antibody deficiency in children with chronic wet cough. Arch Dis Child. 2012 May;97(5):478-80.
Hambleton S, Salem S, Bustamante J, Bigley V, Boisson-Dupuis S, Azevedo J, Fortin A, Haniffa M, Ceron-Gutierrez L, Bacon CM, Menon G, Trouillet C, McDonald D, Carey P, Ginhoux F, Alsina L, Zumwalt TJ, Kong XF, Kumararatne D, Butler K, Hubeau M, Feinberg J, Al-Muhsen S, Cant A, Abel L, Chaussabel D, Döffinger R, Talesnik E, Grumach A, Duarte A, Abarca K, Moraes-Vasconcelos D, Burk D, Berghuis A, Geissmann F, Collin M, Casanova JL, Gros P. IRF8 mutations and human dendritic-cell immunodeficiency. N Engl J Med. 2011 Jul 14;365(2):127-38.
Bigley V, Haniffa M, Doulatov S, Wang XN, Dickinson R, McGovern N, Jardine L, Pagan S, Dimmick I, Chua I, Wallis J, Lordan J, Morgan C, Kumararatne DS, Döffinger R, van der Burg M, van Dongen J, Cant A, Dick JE, Hambleton S, Collin M. The human syndrome of dendritic cell, monocyte, B and NK lymphoid deficiency. J Exp Med. 2011 Feb 14;208(2):227-34.
Schoenmakers E, Agostini M, Mitchell C, Schoenmakers N, Papp L, Rajanayagam O, Padidela R, Ceron-Gutierrez L, Döffinger R, Prevosto C, Luan J, Montano S, Lu J, Castanet M, Clemons N, Groeneveld M, Castets P, Karbaschi M, Aitken S, Dixon A, Williams J, Campi I, Blount M, Burton H, Muntoni F, O'Donovan D, Dean A, Warren A, Brierley C, Baguley D, Guicheney P, Fitzgerald R, Coles A, Gaston H, Todd P, Holmgren A, Khanna KK, Cooke M, Semple R, Halsall D, Wareham N, Schwabe J, Grasso L, Beck-Peccoz P, Ogunko A, Dattani M, Gurnell M, Chatterjee K. Mutations in the selenocysteine insertion sequence-binding protein 2 gene lead to a multisystem selenoprotein deficiency disorder in humans. J Clin Invest. 2010 Dec;120(12):4220-35.
