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
Featured
2021
Journal Article
MyD88 TIR domain higher-order assembly interactions revealed by microcrystal electron diffraction and serial femtosecond crystallography
Clabbers, Max T. B., Holmes, Susannah, Muusse, Timothy W., Vajjhala, Parimala R., Thygesen, Sara J., Malde, Alpeshkumar K., Hunter, Dominic J. B., Croll, Tristan I., Flueckiger, Leonie, Nanson, Jeffrey D., Rahaman, Md. Habibur, Aquila, Andrew, Hunter, Mark S., Liang, Mengning, Yoon, Chun Hong, Zhao, Jingjing, Zatsepin, Nadia A., Abbey, Brian, Sierecki, Emma, Gambin, Yann, Stacey, Katryn J., Darmanin, Connie, Kobe, Bostjan, Xu, Hongyi and Ve, Thomas (2021). MyD88 TIR domain higher-order assembly interactions revealed by microcrystal electron diffraction and serial femtosecond crystallography. Nature Communications, 12 (1) 2578, 1-14. doi: 10.1038/s41467-021-22590-6
Featured
2015
Journal Article
A novel flow cytometric method to assess inflammasome formation
Sester, David P., Thygesen, Sara J., Sagulenko, Vitaliya, Vajjhala, Parimala R., Cridland, Jasmyn A., Vitak, Nazarii, Chen, Kaiwen W., Osborne, Geoffrey W., Schroder, Kate and Katryn J. Stacey (2015). A novel flow cytometric method to assess inflammasome formation. The Journal of Immunology, 194 (1), 455-462. doi: 10.4049/jimmunol.1401110
Featured
2013
Journal Article
AIM2 and NLRP3 inflammasomes activate both apoptotic and pyroptotic death pathways via ASC
Sagulenko, V., Thygesen, S. J., Sester, D. P., Idris, A., Cridland, J. A., Vajjhala, P. R., Roberts, T., Schroder, K., Vince, J. E., Hill, J. M., Silke, J. and Stacey, K. J. (2013). AIM2 and NLRP3 inflammasomes activate both apoptotic and pyroptotic death pathways via ASC. Cell Death and Differentiation, 20 (9), 1149-1160. doi: 10.1038/cdd.2013.37
Featured
2012
Journal Article
The mammalian PYHIN gene family: Phylogeny, evolution and expression
Cridland, Jasmyn A., Curley, Eva Z., Wykes, Michelle N ., Schroder, Kate, Sweet, Matthew J., Roberts, Tara L., Ragan, Mark A., Kassahn, Karin S. and Stacey, Katryn J. (2012). The mammalian PYHIN gene family: Phylogeny, evolution and expression. BMC Evolutionary Biology, 12 (1) 140, 140.1-140.33. doi: 10.1186/1471-2148-12-140
Featured
2009
Journal Article
HIN-200 proteins regulate caspase activation in response to foreign cytoplasmic DNA
Roberts, Tara L., Idris, Adi, Dunn, Jasmyn A., Kelly, Greg M., Burnton, Carol M., Hodgson, Samantha, Hardy, Lani. L., Garceau, Valerie, Sweet, Matthew J., Ross, Ian L., Hume, David A. and Stacey, Katryn J. (2009). HIN-200 proteins regulate caspase activation in response to foreign cytoplasmic DNA. Science, 323 (5917), 1057-1060. doi: 10.1126/science.1169841
Featured
1996
Journal Article
Macrophages ingest and are activated by bacterial DNA
Stacey, K. J., Sweet, M. J. and Hume, D. A. (1996). Macrophages ingest and are activated by bacterial DNA. Journal of Immunology, 157 (5), 2116-2122.
2024
Journal Article
Microcrystal electron diffraction structure of Toll-like receptor 2 TIR-domain-nucleated MyD88 TIR-domain higher-order assembly
Li, Y., Pacoste, L. C., Gu, W., Thygesen, S. J., Stacey, K. J., Ve, T., Kobe, B., Xu, H. and Nanson, J. D. (2024). Microcrystal electron diffraction structure of Toll-like receptor 2 TIR-domain-nucleated MyD88 TIR-domain higher-order assembly. Acta Crystallographica Section D Structural Biology, 80 (9), 699-712. doi: 10.1107/s2059798324008210
2024
Journal Article
o-Vanillin binds covalently to MAL/TIRAP Lys-210 but independently inhibits TLR2
Rahaman, Md. Habibur, Thygesen, Sara J., Maxwell, Michael J., Kim, Hyoyoung, Mudai, Prerna, Nanson, Jeffrey D., Jia, Xinying, Vajjhala, Parimala R., Hedger, Andrew, Vetter, Irina, Haselhorst, Thomas, Robertson, Avril A. B., Dymock, Brian, Ve, Thomas, Mobli, Mehdi, Stacey, Katryn J. and Kobe, Bostjan (2024). o-Vanillin binds covalently to MAL/TIRAP Lys-210 but independently inhibits TLR2. Journal of Enzyme Inhibition and Medicinal Chemistry, 39 (1) 2313055, 2313055. doi: 10.1080/14756366.2024.2313055
2024
Journal Article
Fluorochrome‐labeled inhibitors of caspase‐1 require membrane permeabilization to efficiently access caspase‐1 in macrophages
Thygesen, Sara J, Burgener, Sabrina S, Mudai, Prerna, Monteleone, Mercedes, Boucher, Dave, Sagulenko, Vitaliya, Schroder, Kate and Stacey, Katryn J (2024). Fluorochrome‐labeled inhibitors of caspase‐1 require membrane permeabilization to efficiently access caspase‐1 in macrophages. European Journal of Immunology, 54 (5) 2350515, e2350515. doi: 10.1002/eji.202350515
2023
Journal Article
Kinetics of severe dengue virus infection and development of gut pathology in mice
Pliego Zamora, Adriana, Kim, Jaehyeon, Vajjhala, Parimala R., Thygesen, Sara J., Watterson, Daniel, Modhiran, Naphak, Bielefeldt-Ohmann, Helle and Stacey, Katryn J. (2023). Kinetics of severe dengue virus infection and development of gut pathology in mice. Journal of Virology, 97 (11) ARTN e0125123, e0125123. doi: 10.1128/jvi.01251-23
2023
Conference Publication
Structural evolution of TIR-domain signalosomes in mammalian, plant and bacterial immunity characterized by integrative structural biology
Kobe, Bostjan, Nanson, Jeffrey D., Manik, Mohammad K., Li, Sulin, Gu, Weixi, Pan, Mengqi, Li, Yan, Muusse, Timothy W., Vajjhala, Parimala R, Stacey, Katryn J., Holmes, Susannah, Darmanin, Connie, Clabbers, Max T. B., Xu, Hongyi, Shi, Yun and Ve, Thomas (2023). Structural evolution of TIR-domain signalosomes in mammalian, plant and bacterial immunity characterized by integrative structural biology. XXVI IUCr Congress, Melbourne, VIC Australia, 22-29 August 2023. Hoboken, NJ United States: Wiley-Blackwell. doi: 10.1107/s2053273323093658
2023
Conference Publication
TLR4 TIR domain higher-order assemblies reveal the structural basis of adaptor recruitment in Toll-like receptor signaling pathways
Nanson, J. D., Muusse, T. W., Li, Y., Pan, M., Landsberg, M. J., Vajjhala, P. R., Ve, T., Stacey, K. J. and Kobe, B. (2023). TLR4 TIR domain higher-order assemblies reveal the structural basis of adaptor recruitment in Toll-like receptor signaling pathways. XXVI IUCr Congress, Melbourne, VIC Australia, 22-29 August 2023. Hoboken, NJ United States: Wiley-Blackwell. doi: 10.1107/s2053273323086631
2023
Journal Article
TLR4 phosphorylation at tyrosine 672 activates the ERK/c‐FOS signaling module for LPS‐induced cytokine responses in macrophages
Curson, James E. B., Liu, Liping, Luo, Lin, Muusse, Timothy W., Lucas, Richard M., Gunther, Kimberley S., Vajjhala, Parimala R., Abrol, Rishika, Jones, Alun, Kapetanovic, Ronan, Stacey, Katryn J., Stow, Jennifer L. and Sweet, Matthew J. (2023). TLR4 phosphorylation at tyrosine 672 activates the ERK/c‐FOS signaling module for LPS‐induced cytokine responses in macrophages. European Journal of Immunology, 53 (7) e2250056, e2250056. doi: 10.1002/eji.202250056
2023
Journal Article
SARS-CoV-2 drives NLRP3 inflammasome activation in human microglia through spike protein
Albornoz, Eduardo A., Amarilla, Alberto A., Modhiran, Naphak, Parker, Sandra, Li, Xaria X., Wijesundara, Danushka K., Aguado, Julio, Zamora, Adriana Pliego, McMillan, Christopher L. D., Liang, Benjamin, Peng, Nias Y. G., Sng, Julian D. J., Saima, Fatema Tuj, Fung, Jenny N., Lee, John D., Paramitha, Devina, Parry, Rhys, Avumegah, Michael S., Isaacs, Ariel, Lo, Martin W., Miranda-Chacon, Zaray, Bradshaw, Daniella, Salinas-Rebolledo, Constanza, Rajapakse, Niwanthi W., Wolvetang, Ernst J., Munro, Trent P., Rojas-Fernandez, Alejandro, Young, Paul R., Stacey, Katryn J. ... Woodruff, Trent M. (2023). SARS-CoV-2 drives NLRP3 inflammasome activation in human microglia through spike protein. Molecular Psychiatry, 28 (7), 2878-2893. doi: 10.1038/s41380-022-01831-0
2022
Journal Article
Flow cytometric reporter assays provide robust functional analysis of signaling complexes
Muusse, Timothy W., Lee, Morris Y.L., Kim, Hyoyoung, Parat, Marie-Odile, Nanson, Jeffrey D., Kobe, Bostjan, Vajjhala, Parimala R. and Stacey, Katryn J. (2022). Flow cytometric reporter assays provide robust functional analysis of signaling complexes. Journal of Biological Chemistry, 298 (12) 102666, 102666. doi: 10.1016/j.jbc.2022.102666
2021
Journal Article
A broadly protective antibody that targets the flavivirus NS1 protein
Modhiran, Naphak, Song, Hao, Liu, Lidong, Bletchly, Cheryl, Brillault, Lou, Amarilla, Alberto A., Xu, Xiaoying, Qi, Jianxun, Chai, Yan, Cheung, Stacey T. M., Traves, Renee, Setoh, Yin Xiang, Bibby, Summa, Scott, Connor A. P., Freney, Morgan E., Newton, Natalee D., Khromykh, Alexander A., Chappell, Keith J., Muller, David A., Stacey, Katryn J., Landsberg, Michael J., Shi, Yi, Gao, George F., Young, Paul R. and Watterson, Daniel (2021). A broadly protective antibody that targets the flavivirus NS1 protein. Science, 371 (6525), 190-194. doi: 10.1126/science.abb9425
2020
Journal Article
Manipulation of epithelial cell death pathways by Shigella
Thygesen, Sara J., Pliego‐Zamora, Adriana and Stacey, Katryn J. (2020). Manipulation of epithelial cell death pathways by Shigella. The EMBO Journal, 39 (17), e106202. doi: 10.15252/embj.2020106202
2019
Journal Article
IRF 1 and IRF 2 regulate the non‐canonical inflammasome
Thygesen, Sara J. and Stacey, Katryn J. (2019). IRF 1 and IRF 2 regulate the non‐canonical inflammasome. EMBO reports, 20 (9) e48891, e48891. doi: 10.15252/embr.201948891
2019
Journal Article
Dual targeting of dengue virus virions and NS1 protein with the heparan sulfate mimic PG545
Modhiran, Naphak, Gandhi, Neha S., Wimmer, Norbert, Cheung, Stacey, Stacey, Katryn, Young, Paul R., Ferro, Vito and Watterson, Daniel (2019). Dual targeting of dengue virus virions and NS1 protein with the heparan sulfate mimic PG545. Antiviral Research, 168, 121-127. doi: 10.1016/j.antiviral.2019.05.004
2019
Journal Article
Compromised NLRP3 and AIM2 inflammasome function in autoimmune NZB/W F1 mouse macrophages
Thygesen, Sara J., Takizawa, Karli E., Robertson, Avril A. B., Sester, David P. and Stacey, Katryn J. (2019). Compromised NLRP3 and AIM2 inflammasome function in autoimmune NZB/W F1 mouse macrophages. Immunology and cell biology, 97 (1), 17-28. doi: 10.1111/imcb.12193
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, 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
Gastrointestinal tract involvement in dengue virus pathogenesis
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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