The Walter and Eliza Hall Institute of Medical Research

Dr Ben Croker

Details

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Division: Inflammation

Research Overview

• Genetic analysis of the inflammasome
• Negative regulation of cytokine signalling during inflammation
• Modelling the sepsis syndrome
• Regulation of neutrophil survival during inflammation

Our group uses both forward and reverse genetic approaches to study proteins that regulate inflammation induced by Toll-like receptors (TLRs) and multiprotein complexes called inflammasomes. These host receptors sense microbial structures and tissue damage to drive an inflammatory response to eliminate pathogens or initiate tissue repair.

Altered production of inflammatory molecules or lack of negative regulation of cytokine signal transduction during an innate immune response can provoke tissue damage and trigger autoimmune and inflammatory diseases such as sepsis, rheumatoid arthritis, psoriasis, meningitis, lung disease, inflammatory bowel disease and hepatitis.

Research Interests

• Modulating the inflammasome
• Mechanisms of sepsis in Kir6.1-deficient mice
• Autoinflammatory disease in SHP1 mutant mice – roles for interleukin-1 and neutrophils
• Neutrophil apoptosis

Selected Publications

1. BA Croker, JA O’Donnell, CJ Nowell, D Metcalf, G Dewson, KJ Campbell, KL Rogers, Y Hu, GK Smyth, JG Zhang, M White, K Lackovic, LH Cengia, LA O’Reilly, P Bouillet, S Cory, A Strasser, AW Roberts. Fas-mediated neutrophil apoptosis is accelerated by Bid, Bak and Bax and inhibited by Bcl-2 and Mcl-1. Proc. Nat. Ac. Sci USA 2011 Jul 18. PMID: 21768356 [PubMed - in process]
2. BA Croker, H Kiu, M Pellegrini, J Toe, S Preston, D Metcalf, JA O’Donnell, LH Cengia, K McArthur, NA Nicola, WS Alexander, AW Roberts. IL-6 promotes acute and chronic inflammatory disease in the absence of SOCS3. Immunology and Cell Biology 2011 Apr 26. PMID: 21519345 [PubMed - as supplied by publisher]
3. BA Croker, RS Lewis, JJ Babon, JD Mintern, DE Jenne, D Metcalf, JG Zhang, LH Cengia, JA O’Donnell, AW Roberts. Neutrophils require SHP1 to regulate IL-1β production and prevent inflammatory skin disease. J Immunology 2011, 186:1131-9. PMID: 21160041
4. SL Masters, LA Mielke, AL Cornish, CE Sutton, J O’Donnell, LH Cengia, AW Roberts, IP Wicks, KHG Mills, BA Croker. Regulation of IL-1β by IFNγ is species-specific, limited by SOCS1 and influences IL-17 production. EMBO reports 2010, 11:640-6. PMID: 20596075
5. BA Croker, BR Lawson, M Berger, C Eidenschenk, AL Blasius, EY Moresco, S Sovath, L Cengia, LD Shultz, AN Theofilopoulos, S Pettersson, BA Beutler. Inflammation and autoimmunity caused by a SHP1 mutation depend on IL-1, Myd88, and a microbial trigger. PNAS 2008, 105:15028. PMID: 18806225
6. BA Croker, L Mielke, S Wormald, D Metcalf, H Kiu, WS Alexander, DJ Hilton, AW Roberts. Socs3 maintains the specificity of biological responses to cytokine signals during granulocyte and macrophage differentiation. Experimental Hematology 2008, 36, 786-798. PMID: 18400361
7. BA Croker, H Kiu, SE Nicholson. SOCS regulation of the JAK/STAT signaling pathway. Semin Cell Dev Biol. 2008, 19:414-22.PMID: 18708154
8. BA Croker, K Crozat, M Berger, Y Xia, S Sovath, I Eleftherianos, JL Imler, B Beutler. ATP-sensitive potassium channels mediate survival during infection in mammals and insects. Nature Genetics 2007, Dec 39: 1453-60. PMID: 18026101
9. BA Croker, D Metcalf, L Robb, W Wei, S Mifsud, L DiRago, LA Cluse, KD Sutherland, L Hartley, E Williams, JG Zhang, DJ Hilton, NA Nicola, WS Alexander, AW Roberts. SOCS3 is a critical physiological negative regulator of G-CSF signaling and emergency granulopoiesis. Immunity 2004, 20, 153-165. PMID: 14975238
10. BA Croker, DL Krebs, JG Zhang, S Wormald, TA Willson, EG Stanley, L Robb, CJ Greenhalgh, I Förster, BE Clausen, NA Nicola, D Metcalf, DJ Hilton, AW Roberts, WS Alexander. SOCS3 negatively regulates IL-6 signaling in vivo. Nature Immunology 2003, 4, 540-5. PMID: 12754505

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Current Laboratory Members

Laboratory Head: Ben Croker BSc (Hons) PhD Melb

Postdoctoral Fellow: Mordechay Gerlic B Med Lab Sc. PhD

Postdoctoral Fellow: Man Lyang Kim BSc PhD

Postgraduate Student: Joanne O’Donnell BSc (Hons) Melb