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
2016
Conference Publication
Evolution of cell death responses to cytosolic DNA
Vitak, N., Johnson, K. N., Hume, D. A., Sester, D. P. and Stacey, K. J. (2016). Evolution of cell death responses to cytosolic DNA. ICI 2016 International Congress of Immunology, Melbourne, Australia, 21-26 August 2016. Weinheim, Germany: Wiley. doi: 10.1002/eji.201670200
2016
Conference Publication
Inflammatory response sculpting by neutrophil inflammasomes
Chen, K., Gross, C., Wall, A., Stacey, K., Stow, J., Sweet, M. and Schroder, K. (2016). Inflammatory response sculpting by neutrophil inflammasomes. International Congress of Immunology (ICI), Melbourne, VIC, Australia, 21-26 August 2016. Weinheim, Germany: Wiley - VCH. doi: 10.1002/eji.201670200
2015
Journal Article
Response to comment on "Dengue virus NS1 protein activates cells via Toll-like receptor 4 and disrupts endothelial cell monolayer integrity" and "Dengue virus NS1 triggers endothelial permeability and vascular leak that is prevented by NS1 vaccination"
Stacey, Katryn J., Watterson, Daniel, Modhiran, Naphak and Young, Paul R. (2015). Response to comment on "Dengue virus NS1 protein activates cells via Toll-like receptor 4 and disrupts endothelial cell monolayer integrity" and "Dengue virus NS1 triggers endothelial permeability and vascular leak that is prevented by NS1 vaccination". Science Translational Medicine, 7 (318) 318lr4, 318lr4-318lr4. doi: 10.1126/scitranslmed.aad8657
2015
Journal Article
The inflammasome adaptor ASC induces procaspase-8 death effector domain filaments
Vajjhala, Parimala R., Lu, Alvin, Brown, Darren L., Pang, Siew Wai, Sagulenko, Vitaliya, Sester, David P., Cridland, Simon O., Hill, Justine M., Schroder, Kate, Stow, Jennifer L., Wu, Hao and Stacey, Katryn J. (2015). The inflammasome adaptor ASC induces procaspase-8 death effector domain filaments. Journal of Biological Chemistry, 290 (49), 29217-29230. doi: 10.1074/jbc.M115.687731
2015
Journal Article
Response to Comment on "Deficient NLRP3 and AIM2 Inflammasome Function in Autoimmune NZB Mice".
Sester, David P. and Stacey, Katryn J. (2015). Response to Comment on "Deficient NLRP3 and AIM2 Inflammasome Function in Autoimmune NZB Mice".. Journal of Immunology, 195 (10), 4552-4553. doi: 10.4049/jimmunol.1501930
2015
Journal Article
Dengue virus NS1 protein activates cells via Toll-like receptor 4 and disrupts endothelial cell monolayer integrity
Modhiran, Naphak, Watterson, Daniel, Muller, David A., Panetta, Adele K., Sester, David P., Liu, Lidong, Hume, David A., Stacey, Katryn J. and Young, Paul R. (2015). Dengue virus NS1 protein activates cells via Toll-like receptor 4 and disrupts endothelial cell monolayer integrity. Science Translational Medicine, 7 (304) 304ra142, 1-10. doi: 10.1126/scitranslmed.aaa3863
2015
Journal Article
Deficient NLRP3 and AIM2 Inflammasome Function in Autoimmune NZB Mice.
Sester, David P., Sagulenko, Vitaliya, Thygesen, Sara J., Cridland, Jasmyn A., Loi, Yen Siew, Cridland, Simon O., Masters, Seth L., Genske, Ulrich, Hornung, Veit, Andoniou, Christopher E., Sweet, Matthew J., Degli-Esposti, Mariapia A., Schroder, Kate and Stacey, Katryn J. (2015). Deficient NLRP3 and AIM2 Inflammasome Function in Autoimmune NZB Mice.. Journal of Immunology, 195 (3), 1233-1241. doi: 10.4049/jimmunol.1402859
2015
Journal Article
A novel pathway of cell death in response to cytosolic DNA in Drosophila cells
Vitak, Nazarii, Johnson, Karyn N., Sester, David P. and Stacey, Katryn J. (2015). A novel pathway of cell death in response to cytosolic DNA in Drosophila cells. Journal of Innate Immunity, 7 (2), 212-222. doi: 10.1159/000368276
2014
Journal Article
The Neutrophil NLRC4 Inflammasome Selectively Promotes IL-1β Maturation without Pyroptosis during Acute Salmonella Challenge
Chen, Kaiwen W., Groß, Christina J., Vasquez Sotomayor, Flor, Stacey, Katryn J., Tschopp, Jurg, Sweet, Matthew J. and Schroder, Kate (2014). The Neutrophil NLRC4 Inflammasome Selectively Promotes IL-1β Maturation without Pyroptosis during Acute Salmonella Challenge. Cell Reports, 8 (2), 570-582. doi: 10.1016/j.celrep.2014.06.028
2014
Journal Article
Identification of multifaceted binding modes for pyrin and ASC pyrin domains gives insights into pyrin inflammasome assembly
Vajjhala, Parimala R., Kaiser, Sebastian, Smith, Sarah J., Ong, Qi-Rui, Soh, Stephanie L., Stacey, Katryn J. and Hill, Justine M. (2014). Identification of multifaceted binding modes for pyrin and ASC pyrin domains gives insights into pyrin inflammasome assembly. Journal of Biological Chemistry, 289 (34), 23504-23519. doi: 10.1074/jbc.M114.553305
2014
Journal Article
Mitochondrial apoptosis is dispensable for NLRP3 inflammasome activation but non-apoptotic caspase-8 is required for inflammasome priming
Allam, Ramanjaneyulu, Lawlor, Kate E., Yu, Eric Chi-Wang, Mildenhall, Alison L., Moujalled, Donia M., Lewis, Rowena S., Ke, Francine, Mason, Kylie D., White, Michael J., Stacey, Katryn J., Strasser, Andreas, O'Reilly, Lorraine A., Alexander, Warren, Kile, Benjamin T., Vaux, David L. and Vince, James E. (2014). Mitochondrial apoptosis is dispensable for NLRP3 inflammasome activation but non-apoptotic caspase-8 is required for inflammasome priming. EMBO reports, 15 (9), 982-990. doi: 10.15252/embr.201438463
2013
Journal Article
Molecular mechanism for p202-mediated specific inhibition of aim2 inflammasome activation
Yin, Qian, Sester, David P., Tian, Yuan, Hsiao, Yu-Shan, Lu, Alvin, Cridland, Jasmyn A., Sagulenko, Vitaliya, Thygesen, Sara J., Choubey, Divaker, Hornung, Veit, Walz, Thomas, Stacey, Katryn J. and Wu, Hao (2013). Molecular mechanism for p202-mediated specific inhibition of aim2 inflammasome activation. Cell Reports, 4 (2), 327-339. doi: 10.1016/j.celrep.2013.06.024
2013
Journal Article
Inflammasome-mediated pyroptotic and apoptotic cell death, and defense against infection
Aachoui, Youssef, Sagulenko, Vitaliya, Miao, Edward A. and Stacey, Katryn J. (2013). Inflammasome-mediated pyroptotic and apoptotic cell death, and defense against infection. Current Opinion in Microbiology, 16 (3), 319-326. doi: 10.1016/j.mib.2013.04.004
2012
Journal Article
Malaria infection alters the expression of B-cell activating factor resulting in diminished memory antibody responses and survival
Liu, Xue Q., Stacey, Katryn J., Horne-Debets, Joshua M., Cridland, Jasmyn A., Fischer, Katja, Narum, David, Mackay, Fabienne, Pierce, Susan K. and Wykes, Michelle N. (2012). Malaria infection alters the expression of B-cell activating factor resulting in diminished memory antibody responses and survival. European Journal of Immunology, 42 (12), 3291-3301. doi: 10.1002/eji.201242689
2012
Journal Article
Acute lipopolysaccharide priming boosts inflammasome activation independently of inflammasome sensor induction
Schroder, Kate, Sagulenko, Vitaliya, Zamoshnikova, Alina, Richards, Ayanthi A., Cridland, Jasmyn A., Irvine, Katharine M., Stacey, Katryn J. and Sweet, Matthew J. (2012). Acute lipopolysaccharide priming boosts inflammasome activation independently of inflammasome sensor induction. Immunobiology, 217 (12), 1325-1329. doi: 10.1016/j.imbio.2012.07.020
2012
Journal Article
DEC-205 is a cell surface receptor for CpG oligonucleotides
Lahoud, Mireille H., Ahmet, Fatma, Zhang, Jian-Guo, Meuterb, Simone, Policheni, Antonia N., Kitsoulis, Susie, Lee, Chin-Nien, O’Keeffe, Meredith, Sullivan, Lucy C., Brooks, Andrew G., Berry, Richard, Rossjohn, Jamie, Mintern, Justine D., Vega-Ramos, Javier, Villadangos, Jose A., Nicola, Nicos A., Nussenzweig, Michel C., Stacey, Katryn J., Shortman, Ken, Heath, William R. and Caminschi, Irina (2012). DEC-205 is a cell surface receptor for CpG oligonucleotides. Proceedings of the National Academy of Sciences of the United States of America (PNAS), 109 (40), 16270-16275. doi: 10.1073/pnas.1208796109
2012
Conference Publication
Functional significance of evolutionary divergence in Toll-like receptor-regulated gene expression in human versus mouse
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. European Congress of Immunology, Glasgow, Scotland, 5-8 September 2012. Oxford, United Kingdom: Wiley-Blackwell. doi: 10.1111/imm.12002
2011
Journal Article
Intramacrophage survival of uropathogenic Escherichia coli: differences between diverse clinical isolates and between mouse and human macrophages
Bokil, Nilesh J., Totsika, Makrina, Carey, Alison J., Stacey, Katryn J., Hancock, Viktoria, Saunders, Bernadette M., Ravasi, Timothy, Ulett, Glenn C., Schembri, Mark A. and Sweet, Matthew J. (2011). Intramacrophage survival of uropathogenic Escherichia coli: differences between diverse clinical isolates and between mouse and human macrophages. Immunobiology, 216 (11), 1164-1171. doi: 10.1016/j.imbio.2011.05.011
2011
Journal Article
B cells do not take up bacterial DNA: An essential role for antigen in exposure of DNA to toll-like receptor-9
Roberts, Tara L., Turner, Marian L., Dunn, Jasmyn A., Lenert, Petar, Ross, Ian L., Sweet, Matthew J. and Stacey, Katryn J. (2011). B cells do not take up bacterial DNA: An essential role for antigen in exposure of DNA to toll-like receptor-9. Immunology and Cell Biology, 89 (4), 517-525. doi: 10.1038/icb.2010.112
2011
Journal Article
The immunostimulatory activity of phosphorothioate CpG oligonucleotides is affected by distal sequence changes
Roberts, Tara L., Dunn, Jasmyn A., Sweet, Matthew J., Hume, David A. and Stacey, Katryn J. (2011). The immunostimulatory activity of phosphorothioate CpG oligonucleotides is affected by distal sequence changes. Molecular Immunology, 48 (8), 1027-1034. doi: 10.1016/j.molimm.2011.01.011
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
The contribution of gut bacteria to severe dengue disease
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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