
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
2005
Journal Article
Interaction between conventional dendritic cells and natural killer cells is integral to the activation of effective antiviral immunity
Andoniou, C. E., van Dommelen, S. L. H., Voigt, V., Andrews, D. M., Brizard, G., Asselin-Paturel, C., Delale, T., Stacey, K. J., Trinchieri, G. and Degli-Esposti, M. A. (2005). Interaction between conventional dendritic cells and natural killer cells is integral to the activation of effective antiviral immunity. Nature Immunology, 6 (10), 1011-1019. doi: 10.1038/ni1244
2005
Conference Publication
Regulation and function of toll-like receptor 9 in macrophages
Sweet, Matthew J., Schroder, Kate, Sester, David P., Trieu, Angela, Rehli, Michael, Risvanathan, Kumar, Stacey, Katryn J. and Hume, David A. (2005). Regulation and function of toll-like receptor 9 in macrophages. 7th World Congress on Inflammation, Melbourne, VIC Australia, 20-24 August 2005. Switzerland: Birkhaeuser Science.
2005
Journal Article
LPS regulates a set of genes in primary murine macrophages by antagonising CSF-1 action
Sester, D. P., Trieu, A., Brion, K., Schroder, K., Ravasi, T., Robinson, J. A., McDonald, R. C., Ripoll, V., Wells, C. A., Suzuki, H., Hayashizaki, Y., Stacey, K. J., Hume, D. A. and Sweet, M. J. (2005). LPS regulates a set of genes in primary murine macrophages by antagonising CSF-1 action. Immunobiology, 210 (2-4), 97-107. doi: 10.1016/j.imbio.2005.05.004
2005
Conference Publication
Purified splenic B-cells do not respond to E. coli DNA
Roberts, Tara L., Dann, Jasmyn A., Sweet, Matthew J., Hume, David A., Lenert, Petar and Stacey, Katryn J. (2005). Purified splenic B-cells do not respond to E. coli DNA. 7th World Congress on Inflammation, Melbourne, Australia, 20-24 August 2005. Switzerland: Birkhaeuser Science.
2003
Journal Article
The molecular basis for the lack of immunostimulatory activity of vertebrate DNA
Stacey, Katryn J., Young, Greg R., Clark, Francis, Sester, David P., Roberts, Tara L., Naik, Shalin, Sweet, Matthew J. and Hume, David A. (2003). The molecular basis for the lack of immunostimulatory activity of vertebrate DNA. Journal of Immunology, 170 (7), 3614-3620. doi: 10.4049/jimmunol.170.7.3614
2002
Book Chapter
Phosphorothioate backbone modification changes the pattern of responses to CpG
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. Microbial DNA and host immunity. (pp. 63-77) Totowa, New Jersey: Humana Press. doi: 10.1007/978-1-59259-305-7_6
2002
Journal Article
Colony-stimulating factor-1 suppresses responses to CpG DNA and expression of toll-like receptor 9 but enhances responses to lipopolysaccharide in murine macrophages
Sweet, Matthew J., Campbell, Carol C., Sester, David P., Xu, Damo, McDonald, Rebecca C., Stacey, Katryn J., Hume, David A. and Liew, Foo Y. (2002). Colony-stimulating factor-1 suppresses responses to CpG DNA and expression of toll-like receptor 9 but enhances responses to lipopolysaccharide in murine macrophages. Journal of Immunology, 168 (1), 392-399. doi: 10.4049/jimmunol.168.1.392
2000
Journal Article
G551D cystic fibrosis mice exhibit abnormal regulation of inflammation in lungs and macrophages
Thomas, Gordon R., Costelloe, E. A., Lunn, D. P., Stacey, K. J., Passey, R., McGlinn, E. C., McMorran, B. J., Ahadizadeh, A., Geczy, C. L., Wainwright, B. J. and Hume, D. A. (2000). G551D cystic fibrosis mice exhibit abnormal regulation of inflammation in lungs and macrophages. The Journal of Immunology, 164 (7), 3870-3877. doi: 10.4049/jimmunol.164.7.3870
2000
Journal Article
Phosphorothioate backbone modification modulates macrophage activation by CpG DNA1
Sester, D. P., Naik, S., Beasley, S. J., Hume, D. A. and Stacey, K. J. (2000). Phosphorothioate backbone modification modulates macrophage activation by CpG DNA1. The Journal of Immunology, 165 (8), 4165-4173. doi: 10.4049/jimmunol.165.8.4165
2000
Conference Publication
Replication protein A binds preferentially to immunostimulatory oligonucleotides.
Stacey, K. J., Sester, D. P., Murphy, K. M., Sweet, M. J. and Hume, D. A. (2000). Replication protein A binds preferentially to immunostimulatory oligonucleotides.. -, -, -. Bethesda, MD United States: Federation of American Societies for Experimental Biology.
2000
Journal Article
Macrophage activation by immunostimulatory DNA
Stacey, K. J., Sester, D. P., Sweet, M. J. and Hume, D. A. (2000). Macrophage activation by immunostimulatory DNA. Current Topics in Microbiology and Immunology, 247, 41-58. doi: 10.1007/978-3-642-59672-8_3
2000
Journal Article
Regulation of the urokinase plasminogen activator gene in macrophages by macrophage colony-stimulating factor (CSF-1) is dependent upon the level of cell surface receptor
Fowles, L. F., Stacey, K. J., Marks, D., Hamilton, J. A. and Hume, D. A. (2000). Regulation of the urokinase plasminogen activator gene in macrophages by macrophage colony-stimulating factor (CSF-1) is dependent upon the level of cell surface receptor. Biochemical Journal, 347 (1), 313-320. doi: 10.1042/0264-6021:3470313
1999
Journal Article
Immunostimulatory DNA as an adjuvant in vaccination against Leishmania major
Stacey, Katryn J. and Blackwell, Jenefer M. (1999). Immunostimulatory DNA as an adjuvant in vaccination against Leishmania major. Infection and Immunity, 67 (8), 3719-3726. doi: 10.1128/iai.67.8.3719-3726.1999
1999
Journal Article
The actions of bacterial DNA on murine macrophages
Sester, D. P., Stacey, K. J., Sweet, M. J., Beasley, S. J., Cronau, S. L. and Hume, D. A. (1999). The actions of bacterial DNA on murine macrophages. Journal of Leukocyte Biology, 66 (4), 542-548. doi: 10.1002/jlb.66.4.542
1999
Conference Publication
CpG DNA effects macrophage CSF-1 receptor cell surface expression, proliferation and survival
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. 15th International Congress for Society for Leukocyte Biology, Churchill College, Cambridge UK, 22-26 September, 1999. Bethesda, Maryland: Society for Leukocyte Biology.
1999
Journal Article
Regulation of the plasminogen activator inhibitor-2 (PAI-2) gene in murine macrophages. Demonstration of a novel pattern of responsiveness to bacterial endotoxin
Costelloe, E. O., Stacey, K. J., Antalis, T. M. and Hume, D. A. (1999). Regulation of the plasminogen activator inhibitor-2 (PAI-2) gene in murine macrophages. Demonstration of a novel pattern of responsiveness to bacterial endotoxin. Journal of Leukocyte Biology, 66 (1), 172-183. doi: 10.1002/jlb.66.1.172
1999
Journal Article
Mechanisms of regulation of the MacMarcks gene in macrophages by bacterial lipopolysaccharide
Chang, S. S., Stacey, K. J., Costelloe, E. O., Aderem, A., Hume, D. A. and Chen, J. (1999). Mechanisms of regulation of the MacMarcks gene in macrophages by bacterial lipopolysaccharide. Journal of Leukocyte Biology, 66 (3), 528-534. doi: 10.1002/jlb.66.3.528
1999
Conference Publication
Immunostimulatory DNA promotes factor independent survival of macrophages
Sester, D. P., Sweet, M. J., Stacey, K. J. and Hume, D. A. (1999). Immunostimulatory DNA promotes factor independent survival of macrophages. ComBio 99, Conrad Jupiters, Gold Coast, 27-30 September, 1999. Kent Town, SA: Australian Society for Biochemistry & Molecular Biology.
1999
Journal Article
Bacterial/CpG DNA down-modulates colony stimulating factor-1 receptor surface expression on murine bone marrow-derived macrophages with concomitant growth arrest and factor-independent survival
Sester, D. P., Beasley, S. J., Sweet, M. J., Fowles, L. F., Cronau, S., Stacey, K. J. and Hume, D. A. (1999). Bacterial/CpG DNA down-modulates colony stimulating factor-1 receptor surface expression on murine bone marrow-derived macrophages with concomitant growth arrest and factor-independent survival. Journal of Immunology, 163 (12), 6541-6550.
1998
Journal Article
Persistent activation of mitogen-activated protein kinases p42 and p44 and ets-2 phosphorylation in response to colony-stimulating Factor 1/c-fms Signaling
Fowles, Lindsay F., Martin, Michele L., Nelsen, Lori, Stacey, Katryn J., Redd, Douglas, Clark, Ying Mei, Nagamine, Yoshikune, McMahon, Martin, Hume, David A. and Ostrowski, Michael C. (1998). Persistent activation of mitogen-activated protein kinases p42 and p44 and ets-2 phosphorylation in response to colony-stimulating Factor 1/c-fms Signaling. Molecular and Cellular Biology, 18 (9), 5148-5156. doi: 10.1128/MCB.18.9.5148
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
Molecular analysis of adapter protein interaction with Toll-like receptors
Principal Advisor
Other advisors: Dr Parimala Vajjhala
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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
Toll-like receptor signalling mechanisms
Principal Advisor
Other advisors: Dr Parimala Vajjhala
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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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2024
Doctor Philosophy
Gastrointestinal tract involvement in dengue virus pathogenesis
Principal Advisor
Other advisors: Dr Adriana Pliego Zamora
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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
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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
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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
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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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