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Professor Kate Stacey

Professor

School of Chemistry and Molecular Biosciences
Faculty of Science
katryn.stacey@uq.edu.au
+61 7 336 54640

Overview

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.

Research Interests

  • 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.
  • 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
  • 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.
  • 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.

Qualifications

  • BSc (Hons), The University of Queensland
  • PhD, The University of Queensland

Publications

  • 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

  • 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

  • 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

  • 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

  • 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

  • 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.

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Grants

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Supervision

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Publications

Featured Publications

  • 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

  • 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

  • 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

  • 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

  • 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

  • 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.

Book Chapter

  • Plugging the leak in Dengue shock

    Watterson, Daniel, Modhiran, Naphak, Muller, David A., Stacey, Katryn J. and Young, Paul R. (2018). Plugging the leak in Dengue shock. Dengue and Zika: Control and Antiviral Treatment Strategies. (pp. 89-106) edited by Rolf Hilgenfeld and Subhash G. Vasudevan. Singapore, Singapore: Springer Nature. doi: 10.1007/978-981-10-8727-1_7

  • Assessment of inflammasome formation by flow cytometry

    Sester, David P., Zamoshnikova, Alina, Thygesen, Sara J., Vajjhala, Parimala R., Cridland, Simon O., Schroder, Kate and Stacey, Katryn J. (2016). Assessment of inflammasome formation by flow cytometry. Current protocols in immunology. (pp. 14.40.1-14.40.29) edited by Coligan, John E., Bierer, Barbara, Margulies, David H., Shevach, Ethan M. and Strober, Warren. Hoboken, NJ United States: John Wiley & Sons. doi: 10.1002/cpim.13

  • Methods for delivering DNA to intracellular receptors

    Stacey, Katryn J., Idris, Adi, Sagulenko, Vitaliya, Vitak, Nazarii and Sester, David P. (2016). Methods for delivering DNA to intracellular receptors. Toll-like receptor detection and activation. (pp. 93-106) edited by Claire E. McCoy. New York, NY, United States: Springer Science+Business Media. doi: 10.1007/978-1-4939-3335-8_6

  • 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.

  • 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

  • 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.

  • 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

Journal Article

Conference Publication

  • NLRP3 and AIM2 inflammasome function in autoimmune NZB/W F1 mouse macrophages

    Thygesen, Sara Judith, Sester, David P. and Stacey, Katryn J. (2017). NLRP3 and AIM2 inflammasome function in autoimmune NZB/W F1 mouse macrophages. 5th Annual Meeting of the International Cytokine and Interferon Society (ICIS), Kanazawa, Japan, 29 October - 2 November 2017. London, United Kingdom: Academic Press. doi: 10.1016/j.cyto.2017.09.010

  • Cytosolic DNA, HIN-200 proteins and inflammasome activation

    Stacey, K. J., Vajjhala, P. R., Sagulenko, V, Thygesen, S., Vitak, N. and Sester, D. P. (2016). Cytosolic DNA, HIN-200 proteins and inflammasome activation. International Congress of Immunology (ICI), Melbourne, VIC Australia, 21-26 August 2016. Weinheim, Germany: Wiley.

  • 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

  • Inflammasome function in autoimmunity

    Thygesen, S. J., Sester, D. P., Sagulenko, V. and Stacey, K. J. (2016). Inflammasome function in autoimmunity. International Congress of Immunology (ICI), Melbourne, VIC Australia, 21-26 August 2016. Weinheim, Germany: Wiley-Blackwell.

  • 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

  • Molecular arrangement and activation of procaspases-1 and-8 at inflammasomes

    Vajjhala, P., Lu, A., Brown, D., Sagulenko, V, Schroder, K., Stow, J., Wu, H. and Stacey, K. (2016). Molecular arrangement and activation of procaspases-1 and-8 at inflammasomes. ICI 2016 International Congress of Immunology, Melbourne, Australia, 21-26 August 2016. Weinheim, Germany: Wiley.

  • 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

  • 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

  • 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.

  • 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

  • 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.

  • 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.

  • 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.

  • 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.

  • 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.

  • 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 .

  • 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.

Grants (Administered at UQ)

PhD and MPhil Supervision

Current Supervision

Completed Supervision

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ORCID: 0000-0002-3992-7802

Scopus ID: 7003572022

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