Duke-NUS Graduate Medical School, 8 College Road, S169857. For more information, please visit our website www.duke-nus.edu.sg

1
Program in Emerging Infectious Diseases (EID)
About the Speaker Dr Ashley Mansell is a senior scientist and head of the Toll-Like Receptor (TLR) Signaling Laboratory in the Centre for Innate Immunity and Infectious Diseases, Monash Institute of Medical Research (MIMR), Monash University, Australia. Dr Mansell completed his PhD at Trinity College, Dublin, Ireland. Returning to Australia he formed a TLR research laboratory at MIMR where he has been engaged in studying TLR signal transduction and its role in inflammatory diseases. Dr Mansells research group is interested in understanding and identifying novel TLR and other Pattern Recognition Receptor signal transduction genes that positively and negatively regulate the proinflammatory response following pathogen recognition. Recent studies have focused on viral activation of the inflammasome and RIG-like receptor pathways. Dr Mansells research also investigates the immunomodulation of PRR signaling by pathogens such as their research description of Hepatitis B virus targeting of TLR signaling. Dr Mansell has published his research in the highest ranking journals including Nature, Nature Immunology, PNAS, and the Journal of Biological Chemistry. He heads the Australian TLR research network, TLROZ, and established the Infection and Immunity Special Interest Group within the Australasian Society for Immunology.
Toll-like receptor signaling in innate immunity just what does MAL do By Dr Ashley Mansell Monash Institute of Medical Research Toll-Like Receptor (TLR) Signalling Laboratory Abstract Initiation of the innate immune response requires agonist recognition by pathogen-recognition receptors such as the Toll-like receptors (TLRs). TIR domain-containing adaptors are critical in orchestrating the signal transduction pathways after TLR activation and are responsible for scultping the optimal immune response. MAL/ TIRAP is involved in bridging MyD88 to TLR2 and TLR4 in response to bacterial infection. Our studies have characterised the role of MAL in regulating the activation of innate immunity via NF-?B induction of pro-inflammation and the critical role MAL plays in signal transduction. We have also recently begun investigating the role of the Influenza A virus protein PB1-F2 found in pandemic strains of IAV and its role in inflammation. We show that PB1-F2 from pathogenic IAV induces IL-1? secretion via caspase-1 and the NLRP3 inflammasome in humans and mice. Inflammation induced by PB1-F2 was abrogated in NLRP3 deficient mice. To our knowledge, this is the first characterization of the mechanism of PB1-F2-mediated NLRP3 inflammasome complex activation, providing further understanding of PB1-F2 contribution to the enhanced inflammatory phenotype in pathogenic influenza infections. All are welcome
Date 10 August 2012(Friday) Time 3.00 4.00 pm Host Dr Manoj N Krishnan Program in Emerging Infectious Diseases Venue Duke-NUS, Amphitheatre, 2nd Floor
Duke-NUS Graduate Medical School, 8 College
Road, S169857. For more information, please visit
our website www.duke-nus.edu.sg