Bryan Rg Williams

Publications of Bryan Rg Williams

• HDACi: molecular mechanisms and therapeutic implications in the innate immune system.

  Authors: Bandar Ali Suliman, Dakang Xu, Bryan R G Williams

  Immunology and cell biology. 11/2011; 90(1):23-32.

  Histone deacetylase inhibitors (HDACi) are an emerging class of novel anti-cancer drugs that cause growth arrest, differentiation and apoptosis of tumor cells. In addition, many advances have beenHistone deacetylase inhibitors (HDACi) are an emerging class of novel anti-cancer drugs that cause growth arrest, differentiation and apoptosis of tumor cells. In addition, many advances have been made in understanding the immunoregulation of Toll-like receptors, NOD-like receptors and interferons that have recently generated new momentum for the study of HDACi in immunity as a whole, and in the regulation of these innate signaling pathways specifically. HDACi have shown promise as new anti-inflammatory and immunosuppressant agents. They have also demonstrated great potency and relative selectivity in various human/animal models of inflammatory diseases. This review focuses on recent progress and the current state of HDACi knowledge, as well as the molecular mechanisms and therapeutic potential of HDACi for the treatment of inflammatory diseases and cancers.

• Making sense of viral RNA sensing.

  Authors: Michael P Gantier, Bryan R G Williams

  Molecular therapy : the journal of the American Society of Gene Therapy. 09/2011; 19(9):1578-81.

• siRNA-induced immunostimulation through TLR7 promotes antitumoral activity against HPV-driven tumors in vivo.

  Authors: Norliana Khairuddin, Michael P Gantier, Stephen J Blake, Sherry Y Wu, Mark A Behlke, Bryan Rg Williams, Nigel Aj McMillan

  Immunology and cell biology. 03/2011; 90(2):187-96.

  Oncogene-specific downregulation mediated by RNA interference (RNAi) is a promising avenue for cancer therapy. In addition to specific gene silencing, in vivo RNAi treatment with short interferingOncogene-specific downregulation mediated by RNA interference (RNAi) is a promising avenue for cancer therapy. In addition to specific gene silencing, in vivo RNAi treatment with short interfering RNAs (siRNAs) can initiate immune activation through innate immune receptors including Toll-like receptors, (TLRs) 7 and 8. Two recent studies have shown that activation of innate immunity by addition of tri-phosphate motifs to oncogene-specific siRNAs, or by co-treatment with CpG oligos, can potentiate siRNA antitumor effects. To date, there are no reports on applying such approach against human papillomavirus (HPV)-driven cancers. Here, we characterized the antitumor effects of non-modified siRNAs that can target a specific oncogene and/or recruit the innate immune system against HPV-driven tumors. Following the characterization of silencing efficacy and TLR7 immunostimulatory potential of 15 siRNAs targeting the HPV type 16 E6/E7 oncogenes, we identified a bifunctional siRNA sequence that displayed both potent gene silencing and active immunostimulation effect. In vivo systemic administration of this siRNA resulted in reduced growth of established TC-1 tumors in C57BL/6 mice. Ablation of TLR7 recruitment via 2'O-methyl modification of the oligo backbone reduced these antitumor effects. Further, a highly immunostimulatory, but non-HPV targeting siRNA was also able to exert antitumoral effects although for less prolonged time compared with the bifunctional siRNA. Collectively, our work demonstrates for the first time that siRNA-induced immunostimulation can have antitumoral effects against HPV-driven tumors in vivo, even independent of gene silencing efficacy.

• Latest advances in innate antiviral defence.

  Authors: Aaron Irving, Bryan Rg Williams

  F1000 biology reports. 03/2009; 1:22.

  Recent identification of key components in the pattern recognition receptor pathway of retinoic acid-inducible gene-1-like receptors, coupled with characterisation of a new cytoplasmic DNA-sensingRecent identification of key components in the pattern recognition receptor pathway of retinoic acid-inducible gene-1-like receptors, coupled with characterisation of a new cytoplasmic DNA-sensing molecule, have led to a greater understanding of the role viral nucleic acids play in activating innate immunity. This activation of type I interferon is essential for both limiting viral infection and stimulating activation of the adaptive immune response.