Cancer and Innate Immunity

Research > Centre for Cancer Research > Cancer and Innate Immunity

interferonCancer and Innate Immunity

Research Group Co-Heads: Professor Bryan Williams, Dr Anthony Sadler

Scientists in the Cancer and Innate Immunity laboratory are interested in the role of the innate immune system in the regulation of cell growth and differentiation, as well as antiviral responses. We are investigating the innate immune response to RNAs, in both viral infections and other disease processes, including inflammation and cancer. We are also looking at the roles of transcription factors such as PLZF and ATF3 as regulators of molecular signalling pathways in the innate immune system, focusing on both antiviral responses and immune mechanisms in cancer. In addition, we are focusing on the effect of pro-inflammatory cell signalling on cancer progression and are developing inhibitory therapeutics to suppress tumour growth. Furthermore, we are studying the roles of small RNAs and microRNAs in innate immune pathways and cancer, and are working towards the development of novel therapies.

Recent Achievements:

– We identified the transcription factor PLZF as a key regulator of the interferon-stimulated antiviral response.
– We discovered that protein kinase R counteracts viral entry into cells by inhibiting gelsolin, a key actin-modifying protein.
– We found that the transcription factor ATF3 suppresses metastasis in bladder cancer, by regulating gelsolin-mediated remodelling of the actin cytoskeleton.
– We showed that PKR represses inflammasome activity to control inflammation.
– We discovered that PLZF curbs inflammation from the inflammasome.

Research Projects:

The role of RNA-binding in innate immunity
Role of the inflammatory microenvironment in development of colon cancer
Development of broad-spectrum antivirals
Kinase capture
Role of PKR in metabolism
Regulation of inflammation in cancer
Epigenetic control of inflammatory disease
Inhibition of microRNA-155 in inflammation

Research Group:

Professor Bryan Williams (Research Group Co-Head)
Dr Anthony Sadler (Research Group Co-Head)
Dr Dakang Xu
Dr Claire McCoy
Dr Howard Yim
Dr Afsar Ahmed
Dr Thierry Jarde
Dr Dhanya Sooraj

Selected publications:

Sooraj D, Xu D, Cain JE, Gold DP and Williams BRG (2016) Activating transcription factor 3 expression as a marker of response to the histone deacetylase inhibitor pracinostat. Mol Cancer Ther 15(7):1726-1739.

Yim HCH, Wang D, Yu L, White CL, Faber PW, Williams BRG and Sadler AJ (2016) The kinase activity of PKR represses inflammasome activity. Cell Res 26(3):367-379.

Sadler AJ, Rossello FJ, Yu L, Deane JA, Yuan X, Wang D, Irving AT, Kaparakis-Liaskos M, Gantier MP, Yang H, Yim HCH, Hartland EL, Notini AJ, de Boer S, White SJ, Mansell A, Liu J-P, Watkins DN, Gerondakis S, Williams BRG and Xu D (2015) BTB-ZF transcriptional regulator PLZF modifies chromatin to restrain inflammatory signaling programs. Proc Natl Acad Sci USA 112(5):1535-1540.

Sadler AJ, Suliman BA, Yu L, Yuan X, Wang D, Irving AT, Sarvestani ST, Banerjee A, Mansell AS, Liu J-P, Gerondakis S, Williams BRG and Xu D (2015) The acetyltransferase HAT1 moderates the NF-κB response by regulating the transcription factor PLZF. Nat Commun 6:6795.

Ahmed AU, Sarvestani ST, Gantier MP, Williams BRG and Hannigan GE (2014) Integrin-linked kinase modulates lipopolysaccharide- and Helicobacter pylori-induced nuclear factor kappa B-activated tumor necrosis factor alpha production via regulation of p65 serine 536 phosphorylation. J Biol Chem 289(40):27776-27793.

De Nardo D, Labzin LI, Kono H, Seki R, Schmidt SV, Beyer M, Xu D, Zimmer S, Lahrmann C, Schildberg FA, Vogelhuber J, Kraut M, Ulas T, Kerksiek A, Krebs W, Bode N, Grebe A, Fitzgerald ML, Hernandez NJ, Williams BRG, Knolle P, Kneilling M, Röcken M, Lütjohann D, Wright SD, Schultze JL and Latz E (2014) High-density lipoprotein mediates anti-inflammatory reprogramming of macrophages via the transcriptional regulator ATF3. Nat Immunol 15(2):152-160.

Liu MS, Wang D, Morimoto H, Yim HCH, Irving AT, Williams BRG and Sadler AJ (2014) Molecular dynamics reveal a novel kinase-substrate interface that regulates protein translation. J Mol Cell Biol 6(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 J-P, Sadler AJ, Williams BRG, Shen L and Xu D (2013) ATF3 suppresses metastasis of bladder cancer by regulating gelsolin-mediated remodeling of the actin cytoskeleton. Cancer Res 73(12):3625-3637.

Irving AT, Wang D, Vasilevski O, Latchoumanin O, Kozer N, Clayton AHA, Szczepny A, Morimoto H, Xu D, Williams BRG and Sadler AJ (2012) Regulation of actin dynamics by protein kinase R control of gelsolin enforces basal innate immune defense. Immunity 36(5):795-806.

Xu D, Holko M, Sadler AJ, Scott B, Higashiyama S, Berkofsky-Fessler W, McConnell MJ, Pandolfi PP, Licht JD and Williams BRG (2009) Promyelocytic leukemia zinc finger protein regulates interferon-mediated innate immunity. Immunity 30(6):802-816.