Research
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 protecting from infection.
Publications
1. Biallelic RIPK1 mutations in humans cause severe immunodeficiency, arthritis, and intestinal inflammation.
Cuchet-Lourenço D, Eletto D, Wu C, Plagnol V, Papapietro O, Curtis J, Ceron-Gutierrez L, Bacon CM, Hackett S, Alsaleem B, Maes M, Gaspar M, Alisaac A, Goss E, AlIdrissi E, Siegmund D, Wajant H, Kumararatne D, AlZahrani MS, Arkwright PD, Abinun M, Doffinger R, Nejentsev S. Science. 2018 Aug 24;361(6404):810-813
2. Biallelic JAK1 mutations in immunodeficient patient with mycobacterial infection.
Eletto D, Burns SO, Angulo I, Plagnol V, Gilmour KC, Henriquez F, Curtis J, Gaspar M, Nowak K, Daza-Cajigal V, Kumararatne D, Doffinger R, Thrasher AJ, Nejentsev S. Nat Commun. 2016 Dec 23;7:13992
3. Susceptibility to tuberculosis is associated with variants in the ASAP1 gene encoding a regulator of dendritic cell migration.
Curtis J, Luo Y, Zenner HL, Cuchet-Lourenço D, Wu C, Lo K, Maes M, Alisaac A, Stebbings E, Liu JZ, Kopanitsa L, Ignatyeva O, Balabanova Y, Nikolayevskyy V, Baessmann I, Thye T, Meyer CG, Nürnberg P, Horstmann RD, Drobniewski F, Plagnol V, Barrett JC, Nejentsev S. Nat Genet. 2015 May;47(5):523-527
4. Phosphoinositide 3-kinase δ gene mutation predisposes to respiratory infection and airway damage.
Angulo I, Vadas O, Garçon F, Banham-Hall E, Plagnol V, Leahy TR, Baxendale H, Coulter T, Curtis J, Wu C, Blake-Palmer K, Perisic O, Smyth D, Maes M, Fiddler C, Juss J, Cilliers D, Markelj G, Chandra A, Farmer G, Kielkowska A, Clark J, Kracker S, Debré M, Picard C, Pellier I, Jabado N, Morris JA, Barcenas-Morales G, Fischer A, Stephens L, Hawkins P, Barrett JC, Abinun M, Clatworthy M, Durandy A, Doffinger R, Chilvers ER, Cant AJ, Kumararatne D, Okkenhaug K, Williams RL, Condliffe A, Nejentsev S. Science. 2013 Nov 15;342(6160):866-71
5. Rare variants of IFIH1, a gene implicated in antiviral responses, protect against type 1 diabetes.
Nejentsev S, Walker N, Riches D, Egholm M, Todd JA. Science. 2009 Apr 17;324(5925):387-9
6. Localization of type 1 diabetes susceptibility to the MHC class I genes HLA-B and HLA-A.
Nejentsev S, Howson JM, Walker NM, Szeszko J, Field SF, Stevens HE, Reynolds P, Hardy M, King E, Masters J, Hulme J, Maier LM, Smyth D, Bailey R, Cooper JD, Ribas G, Campbell RD, Clayton DG, Todd JA; Wellcome Trust Case Control Consortium.
Nature. 2007 Dec 6;450(7171):887-92
