MCGM Clinical & Research

RMCH Clinical & Research

MRI Clinical & Research / Kellgren Centre for Rheumatology

University of Manchester

Collaborators

• National Institute for Health Research (NIHR)
• Manchester Biomedical Research Centre (BRC)
• Academy of Medical Sciences
• Medical Research Council (MRC)

• Natural history study of type I interferon driven disorders – Patients, with confirmed molecular diagnoses of an interferonopathy, from throughout the UK can be recruited into the observational study, aiming to increase understanding of these disorders. (Dr Briggs)
• Gene discovery studies in innate immune disease – numerous studies underway with local and world-wide collaborators
• Lupus Extended Phenotype study – this study of the clinical presentation, genetic, RNA and protein profiles of patients with connective tissue diseases (Professor Bruce, Dr Parker, Dr McCarthy, Dr Reynolds, Dr Briggs)
• Improving genomic diagnosis using a combined in silico multiple ‘omics approach (Professor’s Hubbard and Black, Dr’s O’Keefe and Briggs and Mr Rowlands)
• CTPS1 immunodeficiency in the North West of England (Professor Newman, Dr Arkwright, Dr Hughes, Dr Briggs)

• Witzel M, Petersheim D, Fan Y, Bahrami E, Racek T, Rohlfs M, Puchałka J, Mertes C, Gagneur J, Ziegenhain C, Enard W, Stray-Pedersen A, Arkwright PD, Abboud MR, Pazhakh V, Lieschke GJ, Krawitz PM, Dahlhoff M, Schneider MR, Wolf E, Horny HP, Schmidt H, Schäffer AA, Klein C. Chromatin remodelling factor SMARCD2 (BAF60B) regulates transcriptional networks controlling differentiation of neutrophil granulocytes. Nature Genetics 2017, Apr 3.
• Israel L, Wang Y, Bulek K, Mina ED, Zhang Z, Pedergnagna V, Chrabieh M, Lemmens NA, Sancho-Shimizu V, Descatoire M, Lasseau T, Israelsson E, Lorenzo L, Yun L, Belkadi A, Moran A, Weisman LE, Vandenesh F, Batteux F, Weller S, Levin M, Herberg J, Abhyankar A, Prando C, Itan Y, van Wamel W, Picard C, Abel L, Chaussabel D, Li X, Beutler B, Arkwright PD, Casanova JL, Puel A. Human adaptive immunity rescues an inborn error of innate immunity. Cell 2017;Feb 23.
• An J*, Briggs TA*^, Dumax-Vorzet A, Alarcón-Riquelme ME, Belot A, Beresford M, Bruce I, Carvalho C, Chaperot L, Frostegård J, Plumas J, Rice GI, Vyse TJ, Wiedeman A, Crow YJ, Elkon KB^. Tartrate-Resistant Acid Phosphatase Deficiency in the Predisposition to Systemic Lupus Erythematosus. Arthritis Rheumatol. 2016; 69(1): 131-142. (*Equal author contribution, ^Corresponding authors).
• Lyons J, Yu X, Hughes JD, Le QT, Jamil A, Bai Y, Ho N, Zhao M, Liu Y, O’Connell MP, Trivedi N, Nelson C, DiMaggio T, Jones N, Matthews H, Lewis KL, Oler AJ, Carlson RJ, Arkwright PD, Hong C, Agama S, Wilson TM, Tucker S, Zhang Y, McElwee JJ, Pao M, Glover SC, Rothenberg ME, Hohman RJ, Stone KD, Caughey GH, Heller T, Metcalfe DD, Biesecker LG, Schwartz LB, Milner JD. Elevated basal serum typtase identifies a multisystem disorder associated with increased α tryptase copy number. Nat Genet. 2016 Oct 17.
• Reynolds JA, Rosenberg AZ, Smith CK, Sergeant JC, Rice GI, Briggs TA, Bruce IN, Kaplan MJ. Vitamin D Deficiency Is Associated With Endothelial Dysfunction and Increases Type-1 Interferon Gene Expression in a Murine Model of SLE. Arthritis Rheumatol. 2016; 68(12): 2929-2935.
• Briggs TA, Rice GI, Adib N, Ades L, Barete S, Baskar K, Baudouin V, Cebeci N, Clapuyt P, Coman D, De Somer L, Finezilber Y, Frydman M, Guven A, Heritier S, Karall D, Kulkarni ML, Lebon P, Levitt D, Le Merrer M, Linglart A, Livingstone JH, Navarro V, Okenfuss E, Puel A, Revencu N, Scholl-Bürgi S, Vivarelli M, Wouters C, Bader-Meunier B, Crow YJ. Spondyloenchondrodysplasia Due to Mutations in ACP5: A Comprehensive Survey. J Clin Immunol. 2016; 36(3): 220-34.
• Okada S, Markle JG, Deenick EK, Mele F, Averbuch D, Lagos M, Alzahrani M, Al-Muhsen S, Halwani R, Ma CS, Wong N, Soudais C, Henderson LA, Marzouqa H, Schamma J, Gonzalez M, Martinez-Barricarte R, Okada C, Avery DT, Latorre D, Deswarte C, Jabot-Hanin F, Torrado E, Fountain J, Belkadi A, Itan Y, Boisson B, Migaud M, Lindestam Arlehamn CS, Sette A, Breton S, McCluskey J, Rossjohn J, de Villartay JP, Moshous D, Hambleton S, Latour S, Arkwright PD, Picard C, Lantz O, Engelhard D, Kobayashi M, Abel L, Cooper AM, Notarangelo LD, Boisson-Dupuis S, Puel A, Sallusto F, Bustamante J, Tangye SG, Casanova JL. Impairment of IL-17A/F immunity to Candida and IFN-γ immunity to Mycobacterium in humans with inherited RORγT deficiency. Science 2015;349:606-13.
• Zhang, X., Bogunovic, D., Payelle-Brogard, B., Francois-Newton, V., Speer, S.D., Yuan, C., Volpi, S., Li, Z., Sanal, O., Mansouri, D., Tezcan, I., Rice, G.I., Chen, C., Mansouri, N., Mahdaviani, S.A., Itan, Y., Boisson, B., Okada, S., Zeng, L., Wang, X., Jiang, H., Liu, W., Han, T., Liu, D., Ma, T., Wang, B., Liu, M., Liu, J.Y., Wang, Q.K., Yalnizoglu, D., Radoshevich, L., Uze, G., Gros, P., Rozenberg, F., Zhang, S.Y., Jouanguy, E., Bustamante, J., Garcia-Sastre, A., Abel, L., Lebon, P., Notarangelo, L.D., Crow, Y.J., Boisson-Dupuis, S., Casanova, J.L. & Pellegrini, S. Human intracellular ISG15 prevents interferon-alpha/beta over-amplification and auto-inflammation. Nature 517, 89-93 (2015).
• Martin E, Palmic N, Hauck F, Lenior C, Fabrega S, Nitschke P, Mongellaz C, Degli Esposti M, Taylor N, Picard C, Majewski J, Jabado N, Wynn R, Fischer A, Arkwright PD*, Latour S*. Inherited CTP synthase 1 deficiency in humans reveal a central role of CTPS1 induction in proliferation of activated T lymphocytes. Nature 2014, May 28
• Rice, G.I., del Toro Duany, Y., Jenkinson, E.M., Forte, G.M., Anderson, B.H., Ariaudo, G., Bader-Meunier, B., Baildam, E.M., Battini, R., Beresford, M.W., Casarano, M., Chouchane, M., Cimaz, R., Collins, A.E., Cordeiro, N.J., Dale, R.C., Davidson, J.E., De Waele, L., Desguerre, I., Faivre, L., Fazzi, E., Isidor, B., Lagae, L., Latchman, A.R., Lebon, P., Li, C., Livingston, J.H., Lourenco, C.M., Mancardi, M.M., Masurel-Paulet, A., McInnes, I.B., Menezes, M.P., Mignot, C., O’Sullivan, J., Orcesi, S., Picco, P.P., Riva, E., Robinson, R.A., Rodriguez, D., Salvatici, E., Scott, C., Szybowska, M., Tolmie, J.L., Vanderver, A., Vanhulle, C., Vieira, J.P., Webb, K., Whitney, R.N., Williams, S.G., Wolfe, L.A., Zuberi, S.M., Hur, S. & Crow, Y.J. Gain-of-function mutations in IFIH1 cause a spectrum of human disease phenotypes associated with upregulated type I interferon signaling. Nat Genet 46, 503-9 (2014).
• Jeremiah, N., Neven, B., Gentili, M., Callebaut, I., Maschalidi, S., Stolzenberg, M.C., Goudin, N., Fremond, M.L., Nitschke, P., Molina, T.J., Blanche, S., Picard, C., Rice, G.I., Crow, Y.J., Manel, N., Fischer, A., Bader-Meunier, B. & Rieux-Laucat, F. Inherited STING-activating mutation underlies a familial inflammatory syndrome with lupus-like manifestations. J Clin Invest 124, 5516-20 (2014).
• Eckard, S.C., Rice, G.I., Fabre, A., Badens, C., Gray, E.E., Hartley, J.L., Crow, Y.J. & Stetson, D.B. The SKIV2L RNA exosome limits activation of the RIG-I-like receptors. Nat Immunol 15, 839-45 (2014).
• Rice, G.I., Forte, G.M., Szynkiewicz, M., Chase, D.S., Aeby, A., Abdel-Hamid, M.S., Ackroyd, S., Allcock, R., Bailey, K.M., Balottin, U., Barnerias, C., Bernard, G., Bodemer, C., Botella, M.P., Cereda, C., Chandler, K.E., Dabydeen, L., Dale, R.C., De Laet, C., De Goede, C.G., Del Toro, M., Effat, L., Enamorado, N.N., Fazzi, E., Gener, B., Haldre, M., Lin, J.P., Livingston, J.H., Lourenco, C.M., Marques, W., Jr., Oades, P., Peterson, P., Rasmussen, M., Roubertie, A., Schmidt, J.L., Shalev, S.A., Simon, R., Spiegel, R., Swoboda, K.J., Temtamy, S.A., Vassallo, G., Vilain, C.N., Vogt, J., Wermenbol, V., Whitehouse, W.P., Soler, D., Olivieri, I., Orcesi, S., Aglan, M.S., Zaki, M.S., Abdel-Salam, G.M., Vanderver, A., Kisand, K., Rozenberg, F., Lebon, P. & Crow, Y.J. Assessment of interferon-related biomarkers in Aicardi-Goutières syndrome associated with mutations in TREX1, RNASEH2A, RNASEH2B, RNASEH2C, SAMHD1, and ADAR: a case-control study. Lancet Neurol 12, 1159-69 (2013).
• Rice G. I., Kasher P.R., Forte G.M., Mannion N.M., Greenwood S.M., Szynkiewicz M., Dickerson J.E., Bhaskar S.S., Zampini M., Briggs T.A., Jenkinson E.M., Bacino C.A., Battini R., Bertini E., Brogan P.A., Brueton L.A., Carpanelli M., De Laet C., de Lonlay P., Del Toro M., Desguerre I., Fazzi E., Garcia-Cazorla A., Heiberg A., Kawaguchi M., Kumar R., Lin J.P., Lourenco C.M., Male A.M., Marques W. Jr., Mignot C., Olivieri I., Orcesi S., Prabhakar P., Rasmussen M., Robinson R.A., Rozenberg F., Schmidt J.L., Steindl K., Tan T.Y., van der Merwe W.G., Vanderver A., Vassallo G., Wakeling EL., Wassmer E., Whittaker E., Livingston J.H., Lebon P., Suzuki T., McLaughlin P.J., Keegan L.P., O’Connell M.A., Lovell S.C., Crow Y.J. Mutations in ADAR1 cause Aicardi-Goutières syndrome associated with a type I interferon signature. Nat Genet. 2012; 44(11): 1243-8.
• Anderson, B.H., Kasher, P.R., Mayer, J., Szynkiewicz, M., Jenkinson, E.M., Bhaskar, S.S., Urquhart, J.E., Daly, S.B., Dickerson, J.E., O’Sullivan, J., Leibundgut, E.O., Muter, J., Abdel-Salem, G.M., Babul-Hirji, R., Baxter, P., Berger, A., Bonafe, L., Brunstom-Hernandez, J.E., Buckard, J.A., Chitayat, D., Chong, W.K., Cordelli, D.M., Ferreira, P., Fluss, J., Forrest, E.H., Franzoni, E., Garone, C., Hammans, S.R., Houge, G., Hughes, I., Jacquemont, S., Jeannet, P.Y., Jefferson, R.J., Kumar, R., Kutschke, G., Lundberg, S., Lourenco, C.M., Mehta, R., Naidu, S., Nischal, K.K., Nunes, L., Ounap, K., Philippart, M., Prabhakar, P., Risen, S.R., Schiffmann, R., Soh, C., Stephenson, J.B., Stewart, H., Stone, J., Tolmie, J.L., van der Knaap, M.S., Vieira, J.P., Vilain, C.N., Wakeling, E.L., Wermenbol, V., Whitney, A., Lovell, S.C., Meyer, S., Livingston, J.H., Baerlocher, G.M., Black, G.C., Rice, G.I. & Crow, Y.J. Mutations in CTC1, encoding conserved telomere maintenance component 1, cause Coats plus. Nat Genet 44, 338-42 (2012).
• Goldstone, D.C., Ennis-Adeniran, V., Hedden, J.J., Groom, H.C., Rice, G.I., Christodoulou, E., Walker, P.A., Kelly, G., Haire, L.F., Yap, M.W., de Carvalho, L.P., Stoye, J.P., Crow, Y.J., Taylor, I.A. & Webb, M. HIV-1 restriction factor SAMHD1 is a deoxynucleoside triphosphate triphosphohydrolase. Nature 480, 379-82 (2011).
• Briggs T.A., Rice G.I., Daly S., Urquhart J., Gornall H., Bader-Meunier B., Baskar K., Baskar S., Baudouin V., Beresford M.W., Black G.C.M., Dearman R.J., de Zegher F., Foster E.S., Francès C., Hayman A.R., Hilton E., Job-Deslandre C., Kulkarni M.L., Le Merrer M., Linglart A., Lovell S.C., Maurer K., Musset L., Navarro V., Picard C., Puel A., Rieux-Laucat F., Roifman C.M., Scholl-Bürgi S., Smith N., Szynkiewicz M., Wiedeman A., Wouters C., Zeef L.A.H., Casanova J-L., Elkon K.B., Janckila A., Lebon P., Crow Y.J. Tartrate-resistant acid phosphatase deficiency causes a bone dysplasia with autoimmunity and a type I interferon expression signature. Nat Genet. 2011; 43(2): 127-31.