Overview
Background
My work focusses on activation of innate immune cells by pathogen products. Following my PhD at UQ 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 the University of Queensland in where I focussed 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.
Availability
- Professor Kate Stacey is:
- Available for supervision
Fields of research
Qualifications
- Bachelor (Honours) of Science (Advanced), The University of Queensland
- Doctor of Philosophy, The University of Queensland
Research interests
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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.
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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
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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.
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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 long term advances. My laboratory does fundamental research into how the immune system recognises the presence of infections.
Works
Search Professor Kate Stacey’s works on UQ eSpace
1996
Conference Publication
Activation of macrophages by bacterial DNA
Stacey, K. J., Sweet, M. and Hume, D. A. (1996). Activation of macrophages by bacterial DNA. -, -, -. Oxford, United Kingdom: John Wiley & Sons .
1996
Book Chapter
Growth and differentiation of murine macrophages
Hume, D. A., Stacey, K. J., Cassady, A. ., Browne, C. M., Sweet, M. J. and Bertoncello, I. (1996). Growth and differentiation of murine macrophages. Handbook of experimental immunology. (pp. 160.1-160.10) Boston: Wiley-Blackwell.
1995
Journal Article
Regulation of urokinase-type plasminogen activator gene transcription by macrophage colony-stimulating factor
Stacey, Katryn J., Fowles, Lindsay F., Colman, Michael S., Ostrowski, Michael C. and Hume, David A. (1995). Regulation of urokinase-type plasminogen activator gene transcription by macrophage colony-stimulating factor. Molecular and Cellular Biology, 15 (6), 3430-3441. doi: 10.1128/MCB.15.6.3430
1994
Journal Article
RNA synthesis inhibition stabilises urokinase mRNA in macrophages
Stacey, Katryn J., Nagamine, Yoshikuni and Hume, David A. (1994). RNA synthesis inhibition stabilises urokinase mRNA in macrophages. FEBS Letters, 356 (2-3), 311-313. doi: 10.1016/0014-5793(94)01294-6
1993
Journal Article
Electroporation and DNA-dependent cell-death in murine macrophages
Stacey, Katryn J., Ross, Ian L. and Hume, David A. (1993). Electroporation and DNA-dependent cell-death in murine macrophages. Immunology and Cell Biology, 71 (2), 75-85. doi: 10.1038/icb.1993.8
1993
Journal Article
The resistance of macrophage-like tumour cell lines to growth inhibition by lipopolysaccharide and pertussis toxin
Xie, Yue, von Gavel, Stephanie, Cassady, A. Ian, Stacey, Katryn J., Dunn, Timothy L. and Hume, David A. (1993). The resistance of macrophage-like tumour cell lines to growth inhibition by lipopolysaccharide and pertussis toxin. British Journal of Haematology, 84 (3), 392-401. doi: 10.1111/j.1365-2141.1993.tb03092.x
1993
Conference Publication
Regulation of the Urokinase-Type Plasminogen-Activator Gene by Csf-1 and Phorbol Ester
Stacey, K. J., Fowles, L. F., Coleman, M. S., Ostrowski, M. and Hume, D. A. (1993). Regulation of the Urokinase-Type Plasminogen-Activator Gene by Csf-1 and Phorbol Ester. -, -, -. United Kingdom: John Wiley & Sons.
1992
Book Chapter
The regulation of urokinase plasminogen activator gene expression in macrophages
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. Mononuclear Phagocytes: Biology of Monocytes and Macrophages. (pp. 233-240) edited by van Furth, R.. Dordrecht , Netherlands: Kluwer Academic Publishers. doi: 10.1007/978-94-015-8070-0
1991
Journal Article
Constitutive expression of the urokinase plasminogen activator gene in murine RAW264 macrophages involves distal and 5' non-coding sequences that are conserved between mouse and pig
Cassady, A. Ian, Stacey, Katryn J., Nimmo, Karen A., Murphy, Kathleen M., von der Ahe, Dietmar, Pearson, David, Botteri, Florence M., Nagamine, Yoshikuni and Hume, David A. (1991). Constitutive expression of the urokinase plasminogen activator gene in murine RAW264 macrophages involves distal and 5' non-coding sequences that are conserved between mouse and pig. Nucleic Acids Research, 19 (24), 6839-6847. doi: 10.1093/nar/19.24.6839
1991
Journal Article
Effects of female sex hormones on lipid metabolism in the uterine epithelium of the mouse
Stacey, Kate, Beasley, Barbara, Wilce, Peter A. and Martin, Len (1991). Effects of female sex hormones on lipid metabolism in the uterine epithelium of the mouse. International Journal of Biochemistry, 23 (3), 371-376. doi: 10.1016/0020-711X(91)90121-3
Funding
Current funding
Supervision
Availability
- Professor Kate Stacey is:
- Available for supervision
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Supervision history
Current supervision
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Doctor Philosophy
The contribution of gut bacteria to severe dengue disease
Principal Advisor
Other advisors: Dr Adriana Pliego Zamora
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Doctor Philosophy
Gastrointestinal tract involvement in dengue virus pathogenesis
Principal Advisor
Other advisors: Dr Adriana Pliego Zamora
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Doctor Philosophy
Molecular analysis of adapter protein interaction with Toll-like receptors
Principal Advisor
Other advisors: Dr Parimala Vajjhala, Dr Sara Thygesen
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Doctor Philosophy
Toll-like receptor signalling mechanisms
Principal Advisor
Other advisors: Dr Parimala Vajjhala, Dr Sara Thygesen
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Doctor Philosophy
Structural and functional analysis of TIR domain enzymatic activity
Associate Advisor
Other advisors: Dr Parimala Vajjhala, Professor Bostjan Kobe
Completed supervision
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2023
Doctor Philosophy
Molecular analysis of TLR4 signalling
Principal Advisor
Other advisors: Dr Parimala Vajjhala, Professor Bostjan Kobe
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2022
Doctor Philosophy
A process of cytosolic DNA-dependent cell death conserved in evolution
Principal Advisor
Other advisors: Dr Sara Thygesen
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2020
Doctor Philosophy
In vitro and in vivo RNAi screening with a West Nile virus library encoding artificial microRNAs identifies novel host restriction factors.
Principal Advisor
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2018
Doctor Philosophy
Inflammasomes and Autoimmunity
Principal Advisor
Other advisors: Professor Kate Schroder
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2009
Doctor Philosophy
Cellular activation and death in response to cytoplasmic DNA
Principal Advisor
Other advisors: Professor David Hume
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2005
Doctor Philosophy
CELLULAR RESPONSES TO IMMUNOSTIMULATORY DNA
Principal Advisor
Other advisors: Professor David Hume, Professor Matt Sweet
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2017
Doctor Philosophy
Dengue NS1 protein and its implication in dengue pathogenesis
Joint Principal Advisor
Other advisors: Professor Daniel Watterson, Professor Paul Young
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2020
Doctor Philosophy
Exploring the antigenic and immunostimulatory nature of dengue virus non-structural protein 1
Associate Advisor
Other advisors: Professor Daniel Watterson, Professor Paul Young
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2017
Doctor Philosophy
Characterizing copy number alterations in low purity cancers using haplotype phasing
Associate Advisor
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2013
Doctor Philosophy
Identification and characterization of anti-microbial pathways in human macrophages
Associate Advisor
Other advisors: Professor Mark Schembri, Professor Matt Sweet
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2008
Doctor Philosophy
The function and regulation of TLR9
Associate Advisor
Other advisors: Professor Matt Sweet
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2007
Doctor Philosophy
TRANSCRIPTIONAL REGULATION OF THE c-fms PROMOTER BY THE ETS FAMILY OF TRANSCRIPTION FACTORS
Associate Advisor
Other advisors: Professor David Hume
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2003
Doctor Philosophy
MECHANISMS OF ACTION OF BACTERIAL DNA ON MACROPHAGE ACTIVATION
Associate Advisor
Other advisors: Professor David Hume
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