Dr Kate Stacey

NHMRC Research Fellow

School of Chemistry and Molecular Biosciences
Faculty of Science

Affiliate Research Fellow

Institute for Molecular Bioscience
katryn.stacey@uq.edu.au
+61 7 336 54640

Overview

Following my PhD on transcriptional regulation in macrophages I went in 1996 to the University of Cambridge on a CJ Martin Fellowship to work in a molecular parasitology laboratory. I returned to the Institute for Molecular Bioscience at the University of Queensland in 1998 where I continued work on immune cell responses to foreign DNA. I was awarded an ARC Future Fellowship in 2009 to move to the School of Chemistry and Molecular Bioscience, where I also lecture in immunology

Research Interests

  • Recognition of foreign DNA in infections
    Given that the DNA of one organism is structurally similar to another, the fact that DNA can be recognised by the immune system as an indication of infection was initially a surprise. There are at least three systems involved in foreign DNA recognition. Toll-like receptor 9 recognises bacterial or viral DNA being taken up from outside the cell and located within the endosomal system. In this case TLR9 distinguishes self DNA from foreign DNA by recognition of unmethylated CpG sequences which are rare in mammalian DNA. Foreign DNA can also be recognised within the cell cytosol, by two receptors, AIM2 and cGAS. In this case, the basis for recognition is not a foreign DNA structure, but rather an abnormal localisation. AIM2 elicits inflammatory responses to the DNA via inflammasome complex formation, and cGAS induces anti-viral interferon secretion. We study the molecular bases for these pathways of DNA recognition, and their regulation.
  • Pathways of cell death elicited by inflammasomes
    Inflammasomes are large protein complexes which assemble in response to a range of infections, environmental irritants, and other danger signals within the body. Inflammasomes promote release of proteins inducing inflammation, as well as leading to the death of infected cells, as a defensive response. The conventional pathway of inflammasome-induced cell death involves a protease caspase-1, which leads to rapid lysis of the cell. We have recently characterised the parallel activation of caspase-8 by the inflammasome, which leads to a different type of cell death termed apoptosis. The activation of several death pathways may be part of the arms race against pathogens which are trying to subvert these pathways. We are investigating the protein-protein interactions involved in inflammasome formation and caspase activation
  • Innate immune defects in the autoimmune disease lupus
    Autoimmunity arises when the immune system inappropriately attacks the host. Lupus is a condition mediated by antibodies against a range of intracellular proteins and DNA, and leads to damage of a wide range of body tissues. The most serious complications generally arise from deposition of antibody complexes in the kidneys. We propose that imbalance in innate immune responses, such as inflammasome responses, are involved in the initiation of lupus. We are using mouse strains which spontaneously develop lupus-like conditions, as well as patient blood samples, to identify abnormalities in innate immune responses. An experimental approach to inhibiting production of interferon, which is a key driver of lupus, will be trialled.
  • Defence against invading DNA as a fundamental process from insects to vertebrates
    We reason that defence against invading pieces of DNA should be fundamental to the viability of all species. Although evolution can be driven by incorporation of foreign DNA into the genome, accumulation of excessive mutations is likely to be detrimental. The AIM2 protein that elicits cell death in response to foreign DNA in the cytosol is restricted to mammals. We are now investigating novel responses to foreign DNA in insects and birds.

Research Impacts

Basic research allows the discovery of the unexpected, which provides the greatest potential advances. My laboratory does basic research into how the immune system recognises the presence of infections. We are particularly interested in how cells detect the presence of foreign DNA. Through this research, we have made discoveries which are relevant to why autoimmune conditions such as lupus, develop. We are now working on a therapy for lupus. In addition, the pathways of recognition of DNA in the cytoplasm of cells which we study seem to be defensive against cancer. This work is contributing to a fundamental understanding of how cells become cancerous, which may in the future open therapeutic avenues.

Qualifications

  • BSc (Hons), The University of Queensland
  • PhD, The University of Queensland

Publications

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Supervision

View all Supervision

Publications

Featured Publications

Book Chapter

  • Sester, David P., Zamoshnikova, Alina, Thygesen, Sara J., Vajjhala, Parimala R., Cridland, Simon O., Schroder, Kate and Stacey, Katryn J. (2016). Assessment of inflammasome formation by flow cytometry. In Coligan, John E., Bierer, Barbara, Margulies, David H., Shevach, Ethan M. and Strober, Warren (Ed.), Current protocols in immunology (pp. 14.40.1-14.40.29) Hoboken, NJ United States: John Wiley & Sons. doi:10.1002/cpim.13

  • Stacey, Katryn J., Idris, Adi, Sagulenko, Vitaliya, Vitak, Nazarii and Sester, David P. (2016). Methods for delivering DNA to intracellular receptors. In Toll-like receptor detection and activation 2nd ed. (pp. 93-106) New York, NY, United States: Springer Science+Business Media. doi:10.1007/978-1-4939-3335-8_6

  • Stacey, Katryn J., Clark, Francis, Young, Greg R. and Roberts, Tara L. (2008). Discrimination of self and non-self DNAs. In Ken J. Ishii and Shizuo Akira (Ed.), Nucleic Acids in Innate Immunity (pp. 85-100) Boca Raton, FL, USA: CRC Press.

  • Stacey, K. J., Sester, D. P., Naik, S., Roberts, T., Sweet, M. J. and Hume, D. A. (2002). Phosphorothioate backbone modification changes the pattern of responses to CpG. In Microbial DNA and Host Immunity (pp. 63-77) Totowa, New Jersey: Humana Press.

  • Hume, D. A., Stacey, K. J., Cassady, A. ., Browne, C. M., Sweet, M. J. and Bertoncello, I. (1996). Growth and differentiation of murine macrophages. In Handbook of experimental immunology (pp. 160.1-160.10) Boston: Wiley-Blackwell.

  • Stacey, K. J., Cassady, A. I., Nimmo, K. A., Murphy, K. M., von der Ahe, D., Pearson, D., Botteri, F., Nagamine, Y. and Hume, D. A. (1992). The regulation of urokinase plasminogen activator gene expression in macrophages. In van Furth, R. (Ed.), Mononuclear Phagocytes: Biology of Monocytes and Macrophages (pp. 233-240) Dordrecht , Netherlands: Kluwer Academic Publishers. doi:10.1007/978-94-015-8070-0

Journal Article

Conference Publication

  • Vitak, N., Johnson, K. N., Hume, D. A., Sester, D. P. and Stacey, K. J. (2016). Evolution of cell death responses to cytosolic DNA. In: ICI 2016 International Congress of Immunology, Melbourne, Australia, (494). 21-26 August 2016. doi:10.1002/eji.201670200

  • Sweet, M. J., Schroder, K., Irvine, K. M., Taylor, M., Bokil, N. J., Broomfield, S., Schembri, M. A., Stacey, K. J. and Hume, D. A. (2012). Functional significance of evolutionary divergence in Toll-like receptor-regulated gene expression in human versus mouse. In: Abstracts of the European Congress of Immunology. European Congress of Immunology, Glasgow, Scotland, (297-297). 5-8 September 2012. doi:10.1111/imm.12002

  • Stacey, K. J., Roberts, T. L., Idris, A., Dunn, A., Hume, D. A. and Ross, I. L. (2005). A detection system for viral dsDNA?. In: Tissue Antigens. Proceedings of: Genetics and The Immune Response'Abstracts of the 35th Annual Scientific Meeting of the Australasian Society for Immunology and 14th International HLA & Immunogenetics Workshop. 35th Annual Scientific Meeting of the Australasian Society for Immunology and 14th International HLA & Immunogenetics Workshop, Melbourne, Australia, (550-551). 29 November - 2 December 2005. doi:10.1111/j.1399-0039.2005.00523.x

  • Idris, A., Ross, I. L. and Stacey, K. J. (2005). Cellular activation and apoptosis in response to transfected dsDNA - A novel foreign nucleic acid detection system. In: Tissue Antigens. Proceedings of: Genetics and The Immune Response'Abstracts of the 35th Annual Scientific Meeting of the Australasian Society for Immunology and 14th International HLA & Immunogenetics Workshop. 35th Annual Scientific Meeting of the Australasian Society for Immunology and 14th International HLA & Immunogenetics Workshop, Melbourne, Australia, (449-449). 29 November - 2 December 2005. doi:10.1111/j.1399-0039.2005.00523.x

  • Sester, D. P., Beasley, S. J., Sweet, M. J., Stacey, K. J. and Hume, D. A. (1999). CpG DNA effects macrophage CSF-1 receptor cell surface expression, proliferation and survival. In: Innate Resistant to Infection, Society for Leukocyte Biology. 15th International Congress for Society for Leukocyte Biology, Churchill College, Cambridge UK, (). 22-26 September, 1999.

  • Sester, D. P., Sweet, M. J., Stacey, K. J. and Hume, D. A. (1999). Immunostimulatory DNA promotes factor independent survival of macrophages. In: Combined Conference Abstracts: 43rd Annual ASBMB, 18th Annual ANZSCDB and 39th Annual ASPP. ComBio 99, Conrad Jupiters, Gold Coast, (Sym-45-04). 27-30 September, 1999.

Grants (Administered at UQ)

PhD and MPhil Supervision

Current Supervision

  • Doctor Philosophy — Principal Advisor

  • Doctor Philosophy — Principal Advisor

    Other advisors:

  • Doctor Philosophy — Associate Advisor

Completed Supervision