Research Group Head
Research in the group currently focuses on three molecules, the protein kinase R, the interferon-induced helicase 1, and the zinc-finger and BTB-domain containing 16, that together detect stress, transduce cell signals and induce gene responses that control inflammation. Through these three molecules, group head Dr Sadler investigates a progression of immune pathologies from the initial responses to infection, through the development of persistent inflammatory conditions (colitis), to established chronic autoimmune diseases (type I diabetes and lupus).
- Treating infection-induced immune pathogenesis
- Evaluating interferon therapy against colitis
- Determining innate immune responses that induce type I diabetes
- Targeting cytokine signalling in systemic lupus erythematosus
Our research focus
Dou Y, Yim HCH, Kirkwood CD, Williams BRG, Sadler AJ (2017) The innate immune receptor MDA5 limits rotavirus infection but promotes cell death and pancreatic inflammation. EMBO J 36:2742-2757.
Wang D, de Weerd NA, Willard B, Polekhina G, Williams BRG, Sadler AJ (2017) Auto-phosphorylation represses protein kinase R activity. Sci Rep 7:44340.
Yim HCH, Wang D, Yu L, White CL, Faber PW, Williams BRG, Sadler AJ (2016) The kinase activity of PKR represses inflammasome activity. Cell Res 26:367-379.
Sadler AJ, Rossello FJ, Yu L, Deane JA, Yuan X, Wang D, Irving AT, Kaparakis-Liaskos M, Gantier MP, Ying H, Yim HCH, Hartland EL, Notini AJ, de Boer S, White SJ, Mansell A, Liu JP, Watkins DN, Gerondakis S, Williams BRG, Xu D (2015) The BTB-ZF transcriptional regulator PLZF modifies chromatin to restrain inflammatory signaling programs. Proc Natl Acad Sci USA 112:1535-1540.
Sadler AJ, Suliman BA, Yu L, Yuan X, Wang D, Irving AT, Sarvestani ST, Banerjee A, Mansell AS, Liu JP, Gerondakis S, Williams BR, Xu D (2015) The acetyltransferase HAT1 moderates the NF-kB response by regulating the transcription factor PLZF. Nat Commun 6:6795.
Liu MS, Wang D, Morimoto H, Yim HCH, Irving AT, Williams BRG, Sadler AJ (2014) Molecular dynamics reveal a novel kinase-substrate interface that regulates protein translation. J Mol Cell Biol 6:473-485.
Yuan X, Yu L, Li J, Xie G, Rong T, Zhang L, Chen J, Meng Q, Irving AT, Wang D, Williams ED, Liu JP, Sadler AJ, Williams BRG, Shen L, Xu D (2013) ATF3 suppresses metastasis of bladder cancer by regulating gelsolin-mediated remodeling of the actin cytoskeleton. Cancer Res 73:3625-3637.
Irving AT, Wang D, Vasilevski O, Latchoumanin O, Kozer N, Clayton AH, Szczepny A, Morimoto H, Xu D, Williams BRG, Sadler AJ (2012) Regulation of actin dynamics by protein kinase R control of gelsolin enforces basal innate immune defense. Immunity 36:795-806.
Sadler AJ, Latchoumanin O, Hawkes D, Mak J, Williams BRG (2009) An antiviral response directed by PKR phosphorylation of the RNA helicase A. PLoS Pathog 5:e1000311.
Xu D, Holko M, Sadler AJ, Scott B, Higashiyama S, Berkofsky-Fessler W, McConnell MJ, Pandolfi PP, Licht JD, Williams BRG (2009) Promyelocytic leukemia zinc finger protein regulates interferon-mediated innate immunity. Immunity 30:802-816.
Chakrabarti A, Sadler AJ, Kar N, Young HA, Silverman RH, Williams BRG (2008) Protein kinase R-dependent regulation of interleukin-10 in response to double-stranded RNA. J Biol Chem 283:25132-25139.
Sadler AJ, Williams BRG (2008) Interferon-inducible antiviral effectors. Nat Rev Immunol 8:559-568.