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Cytokine Biology Group
Professor Geczy (CG) has been funded continuously via NHMRC Project Grants as CI-A since 1978, covering basic themes relevant to inflammation. Her group is also funded from commercial sources. She was the first, worldwide, to develop neutralising antibodies to a cytokine, and to verify their relevance in disease processes. Her work on cellular procoagulants discovered the link between inflammation and coagulation and has underpinned a huge area of basic research by other groups that is now being translated into clinical practice. Her work on the roles of S100 proteins has brought a new level of understanding to the pathogenesis of inflammation.
Current Projects
The Cytokine Research Group has two main research themes: biology of the S100 proteins and the role of cellular procoagulants in vascular disease and inflammation. New research shows the importance of the S100 proteins as positive and negative inflammatory regulators affecting leucocyte activation, migration and host defence on the one hand, and as anti-oxidant sinks with protective properties, on the other. The activation of blood coagulation by cellular procoagulants activated by cytokines and other inflammatory mediators is shedding new light on mechanisms of thrombosis in coronary artery disease and in other chronic inflammatory disorders such as rheumatoid arthritis.
Techniques used include in-house generated ELISAs to measure S100 proteins in serum; production of antibodies to detect protein expression by Western blotting and immunohistochemistry of normal and diseased tissues; culture of numerous cell types including blood mononuclear cells and mast cells from human cord blood; molecular analysis including real-time PCR to detect gene expression, promotor and transcriptional analyses; functional assays such as measurement of cell procoagulants, chemotaxis, mast cell activation, induction of cytokines in vitro and intravital microscopy to measure leukocyte-endothelial cell interactions in vivo; immunoprecipitation and GST-pull-down assays; protein expression systems and structure-function analysis; assessment of post-translational products by proteomics and mass spectrometry. The group uses animal models affecting mast cell activation and/or leucocyte recruitment, endotoxin-induced alveolitis, UV-induced skin damage and various skin test reactions. The group undertakes extensive collaborative work with leading molecular and structural biologists at the University of Queensland and with other research groups in Australia and abroad.
Researchers
Professor Carolyn Geczy, Chief Investigator
Dr Kenneth Hsu, Post Doctoral Scientist
Dr Wei xing Yan, Post Doctoral Scientist
Esther Lim, Research Assistant
Dr Ikuko Endoh, PhD Student
Jesse Goyette, PhD Student
Dr Yasumi Endoh, PhD Student
Selected Publications
Lau W., Devery J.M. and Geczy C.L. (1995). A chemotactic S100 peptide enhances scavenger receptor and mac-1 expression, and cholesteryl ester accumulation in murine peritoneal macrophages in vivo. J Clin Invest., 95:1957-1965
Harrison C.A., Raftery M.J., Walsh J., Alewood P., Iismaa S.E., Thliveris S., and Geczy C.L. (1999) Oxidation regulates the inflammatory properties of the murine S100 protein, S100A8. J. Biol. Chem. 274:8561-8569
Nakagomi A., Freedman B.S. and Geczy C.L. (2000) Interferon and LPS potentiate monocyte tissue induction by C-reactive protein: relationship with age, sex and hormone replacement treatment. Circulation. 101:1785-1791.
Xu K., Yen T. and Geczy C.L. Interleukin-10 upregulates macrophage expression of the S100 protein, S100A8. (2001). J. Immunol. 166:6358-6366.
Yang Z., Tao T., Raftery M.J., Youssef P., Di Girolamo N. and Geczy C.L. Pro-inflammatory properties of the human S100 protein, S100A12. (2001). J. Leukocyte Biol. 69:986-994
Raftery, M.J., Yang, Z., Valenzuela, S.M. and Geczy C.L. Novel intra- and inter-molecular sulfonamide bonds in S100A8 produced by hypochlorite oxidation. (2001) J. Biol. Chem. 276:33393-33401.
Ravasi, T., Hsu, K., Goyette, J., Schroder, K., Yang, Z., Rahimi, F., Miranda, L.P., Alewood, P.F., Hume, D.A., Geczy, C.L. (2004) Probing the S100 protein family through genomic and functional analysis. Genomics, 84:10-22. [Cover photo].
Hsu, K., Passey, R.J., Endoh, Y., Rahimi, F., Youssef, P., Yen, T., Geczy, C.L. (2005) Regulation of S100A8 by glucocorticoids. Journal of Immunology 174: 2318-2326
Rahimi, F., Hsu, K., Endoh, Y., Geczy, C.L. (2005) FGF-2,, IL-1b and TGF-b regulate fibroblast expression of S100A8. FEBS Journal 272: 1-17 [Cover photo]
Cai, H., Song, C., Geok San Lim, I., Krillis, S.A., Geczy, C.L., McNeil, H.P. (2005) Importance of C-reactive protein in regulating monocyte tissue factor expression in patients with inflammatory rheumatic diseases. accepted; Journal of Rheumatology, 32:1224-12231.
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Chief Investigator
Professor Carolyn Geczy
T (02) 9385 2777
F (02) 9385 1389
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Personal Research Profile
From left to right: (standing) Dr Carolyn Geczy, Owen Huynh, Dr Yasumi Endoh, Jesse Goyette, Dr Farid Rahimi, Dr Ken Hsu (seated) Dr Ikuko Endoh, Dr Nicodemus Tedla, Dr Wei-Xing Yan
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