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
2011
Journal Article
Macrophage activation and differentiation signals regulate Schlafen-4 gene expression: Evidence for Schlafen-4 as a modulator of myelopoiesis
Van Zuylen, Wendy J., Garceau, Valerie, Idris, Adi, Schroder, Kate, Irvine, Katharine M., Lattin, Jane E., Ovchinnikov, Dmitry A., Perkins, Andrew C., Cook, Andrew D., Hamilton, John A., Hertzog, Paul J., Stacey, Katryn J., Kellie, Stuart, Hume, David A. and Sweet, Matthew J. (2011). Macrophage activation and differentiation signals regulate Schlafen-4 gene expression: Evidence for Schlafen-4 as a modulator of myelopoiesis. PLoS One, 6 (1) e15723, e15723-1-e15723-13. doi: 10.1371/journal.pone.0015723
2010
Journal Article
A clear link between endogenous retroviral LTR activity and Hodgkin's lymphoma
Stacey, Katryn J. and Sagulenko, Vitaliya (2010). A clear link between endogenous retroviral LTR activity and Hodgkin's lymphoma. Cell Research, 20 (8), 869-871. doi: 10.1038/cr.2010.96
2010
Journal Article
A visual framework for sequence analysis using n-grams and spectral rearrangement
Maetschke, Stefan R., Kassahn, Karin S., Dunn, Jasmyn A., Han, Siew-Ping, Curley, Eva Z., Stacey, Katryn J. and Ragan, Mark A. (2010). A visual framework for sequence analysis using n-grams and spectral rearrangement. Bioinformatics, 26 (6) btq042, 737-744. doi: 10.1093/bioinformatics/btq042
2009
Journal Article
TLR-9-independent effects of inhibitory oligonucleotides on macrophages responses to S. typhimurium
Trieu, Angela, Bokil, Nilesh, Dunn, Jasmyn A., Roberts, Tara L., Xu, Damo, Liew, Foo Y., Hume, David A., Stacey, Katryn J. and Sweet, Matthew J. (2009). TLR-9-independent effects of inhibitory oligonucleotides on macrophages responses to S. typhimurium. Immunology and Cell Biology, 87 (3), 218-225. doi: 10.1038/icb.2008.95
2008
Book Chapter
Discrimination of self and non-self DNAs
Stacey, Katryn J., Clark, Francis, Young, Greg R. and Roberts, Tara L. (2008). Discrimination of self and non-self DNAs. Nucleic Acids in Innate Immunity. (pp. 85-100) edited by Ken J. Ishii and Shizuo Akira. Boca Raton, FL, USA: CRC Press.
2007
Journal Article
Differential effects of CpG DNA on IFN-beta induction and STAT1 activation in murine macrophages versus dendritic cells: Alternatively activated STAT1 negatively regulates TLR signaling in macrophages
Schroder, K., Spille, M., Pilz, A., Lattin, J., Bode, K. A., Irvine, K. M., Burrows, A. D., Ravasi, T., Weighardt, H., Stacey, K. J., Decker, T., Hume, D. A., Dalpke, A. H. and Sweet, M. J. (2007). Differential effects of CpG DNA on IFN-beta induction and STAT1 activation in murine macrophages versus dendritic cells: Alternatively activated STAT1 negatively regulates TLR signaling in macrophages. Journal of Immunology, 179 (6), 3495-3503. doi: 10.4049/jimmunol.179.6.3495
2007
Journal Article
Plasmodium strain determines dendritic cell function essential for survival from malaria
Wykes, Michelle N., Liu, Xue Q., Beattie, Lynette, Stanisic, Danielle I., Stacey, Katryn J., Smyth, Mark J., Thomas, Ranjeny and Good, Michael F. (2007). Plasmodium strain determines dendritic cell function essential for survival from malaria. PLoS Pathogens, 3 (7), e96-0904-e96-0912. doi: 10.1371/journal.ppat.0030096
2007
Journal Article
PU.1 and ICSBP control constitutive and IFN-gamma-regulated Tlr9 gene expression in mouse macrophages
Schroder, Kate, Lichtinger, Monika, Irvine, Katharine M., Brion, Kristian, Trieu, Angela, Ross, Ian L., Ravasi, Timothy, Stacey, Katryn J., Rehli, Michael, Hume, David A. and Sweet, Matthew J. (2007). PU.1 and ICSBP control constitutive and IFN-gamma-regulated Tlr9 gene expression in mouse macrophages. Journal of Leukocyte Biology, 81 (6), 1577-1590. doi: 10.1189/jlb.0107036
2006
Journal Article
CpG DNA activates survival in murine macrophages through TLR9 and the phosphatidylinositol 3-kinase-Akt pathway
Sester, D. P., Brion, K., Trieu, A., Goodridge, H. S., Roberts, T. L., Dunn, J., Hume, D. A., Stacey, K. J. and Sweet, M. J. (2006). CpG DNA activates survival in murine macrophages through TLR9 and the phosphatidylinositol 3-kinase-Akt pathway. Journal of Immunology, 177 (7), 4473-4480. doi: 10.4049/jimmunol.177.7.4473
2006
Journal Article
Higher-order CpG-DNA stimulation reveals distinct activation requirements for marginal zone and follicular B cells in lupus mice
Brummel, Rachel, Roberts, Tara L., Stacey, Katryn J. and Lenert, Petar (2006). Higher-order CpG-DNA stimulation reveals distinct activation requirements for marginal zone and follicular B cells in lupus mice. European Journal of Immunology, 36 (7), 1951-1962. doi: 10.1002/eji.200535734
2006
Journal Article
DNA Motifs Suppressing TLR9 Responses
Trieu, A., Roberts, T. L., Dunn, J. A., Sweet, M. J. and Stacey, K. J. (2006). DNA Motifs Suppressing TLR9 Responses. Critical reviews in Immunology, 26 (6), 527-544. doi: 10.1615/CritRevImmunol.v26.i6.50
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.
2005
Conference Publication
Cellular activation and apoptosis in response to transfected dsDNA - A novel foreign nucleic acid detection system
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. 35th Annual Scientific Meeting of the Australasian Society for Immunology and 14th International HLA & Immunogenetics Workshop, Melbourne, Australia, 29 November - 2 December 2005. Copenhagan, Denmark: John Wiley & Sons. doi: 10.1111/j.1399-0039.2005.00523.x
2005
Journal Article
Cutting edge: Species-specific TLR9-mediated recognition of CpG and non-CpG phosphorothioate-modified ohgonucleotides
Roberts, T. L., Sweet, M. J., Hume, D. A. and Stacey, K. J. (2005). Cutting edge: Species-specific TLR9-mediated recognition of CpG and non-CpG phosphorothioate-modified ohgonucleotides. Journal of Immunology, 174 (2), 605-608. doi: 10.4049/jimmunol.174.2.605
2005
Journal Article
The phasevarion: A genetic system controlling coordinated, random switching of expression of multiple genes
Srikhanta, Y. N., Maguire, T. L., Stacey, K. J., Grimmond, S. M. and Jennings, M. P. (2005). The phasevarion: A genetic system controlling coordinated, random switching of expression of multiple genes. Proceedings of The National Academy of Sciences of The United States of America, 102 (15), 5547-5551. doi: 10.1073/pnas.0501169102
2005
Journal Article
Differences in macrophage activation by bacterial DNA and CpG-containing oligonucleotides
Roberts, T. L., Dunn, J. A., Terry, T. D., Jennings, M. P., Hume, D. A., Sweet, M. J. and Stacey, K. J. (2005). Differences in macrophage activation by bacterial DNA and CpG-containing oligonucleotides. Journal of Immunology, 175 (6), 3569-3576. doi: 10.4049/jimmunol.175.6.3569
2005
Conference Publication
Blockade of CSF-1 action enhances CpG DNA responses in vivo
Trieu, Angela, Cronau, Steve, Roberts, Tara, Lottin, Jane, Vlahos, Ross, Stacey, Katryn J., Hume, David A. and Sweet, Matthew J. (2005). Blockade of CSF-1 action enhances CpG DNA responses in vivo. 7th World Congress on Inflammation, Melbourne, Australia, 20-24 August 2005. Switzerland: Birkhaeuser Science.
2005
Conference Publication
A detection system for viral dsDNA?
Stacey, K. J., Roberts, T. L., Idris, A., Dunn, A., Hume, D. A. and Ross, I. L. (2005). A detection system for viral dsDNA?. 35th Annual Scientific Meeting of the Australasian Society for Immunology and 14th International HLA & Immunogenetics Workshop, Melbourne, Australia, 29 November - 2 December 2005. Copenhagan, Denmark: John Wiley & Sons. doi: 10.1111/j.1399-0039.2005.00523.x
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
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
Gastrointestinal tract involvement in dengue virus pathogenesis
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, Dr Sara Thygesen
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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
The contribution of gut bacteria to severe dengue disease
Principal Advisor
Other advisors: Dr Adriana Pliego Zamora
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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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