Dr Antiopi Varelias

Honorary Fellow

Royal Brisbane Clinical Unit
Faculty of Medicine

Overview

Publications

  • Bunting, Mark D., Varelias, Antiopi, Souza-Fonseca-Guimaraes, Fernando, Schuster, Iona S., Lineburg, Katie E., Kuns, Rachel D., Fleming, Peter, Locke, Kelly R., Huntington, Nicholas D., Blazar, Bruce R., Lane, Steven W., Tey, Siok-Keen, MacDonald, Kelli P. A., Smyth, Mark J., Degli-Esposti, Mariapia A. and Hill, Geoffrey R. (2017) GVHD prevents NK-cell-dependent leukemia and virus-specific innate immunity. Blood, 129 5: 630-642. doi:10.1182/blood-2016-08-734020

  • Varelias, Antiopi, Ormerod, Kate L., Bunting, Mark D., Koyama, Motoko, Gartlan, Kate H., Kuns, Rachel D., Lachner, Nancy, Locke, Kelly R., Lim, Chun Y., Henden, Andrea S., Zhang, Ping, Clouston, Andrew D., Hasnain, Sumaira Z., McGuckin, Michael A., Blazar, Bruce R., MacDonald, Kelli P. A ., Hugenholtz, Philip and Hill, Geoffrey R. (2017) Acute graft-versus-host disease is regulated by an IL-17-sensitive microbiome. Blood, 129 15: 2172-2185. doi:10.1182/blood-2016-08-732628

  • Gartlan, Kate H., Markey, Kate A., Varelias, Antiopi, Bunting, Mark D., Koyama, Motoko, Kuns, Rachel D., Raffelt, Neil C., Olver, Stuart D., Lineburg, Katie E., Cheong, Melody, Teal, Bianca E., Lor, Mary, Comerford, Iain, Teng, Michele W. L., Smyth, Mark J., McCluskey, James, Rossjohn, Jamie, Stockinger, Brigitta, Boyle, Glen M., Lane, Steven W., Clouston, Andrew D., McColl, Shaun R., MacDonald, Kelli P. A. and Hill, Geoffrey R. (2015) Tc17 cells are a proinflammatory, plastic lineage of pathogenic CD8<sup>+</sup> T cells that induce GVHD without antileukemic effects. Blood, 126 13: 1609-1620. doi:10.1182/blood-2015-01-622662

View all Publications

Available Projects

  • Supervisors: Dr Antiopi Varelias (antiopi.varelias@qimrberghofer.edu.au) and Prof Geoff Hill (geoff.hill@qimrberghofer.edu.au)

    Background: Chemotherapy/radiation treatment during conditioning damages intestinal epithelium resulting in systemic exposure to microbial products normally sequestered in the intestinal lumen, in addition to a marked cytokine release which we have previously published. These microbial products can influence graft-versus-host disease (GVHD) and transplant outcome. Numerous approaches targeting the gut microbiome to harness GVHD (eg. gut decontaminating antibiotics, introduction of beneficial bacteria or targeting anaerobic bacteria) have been attempted with some effect but there is no consensus between bone marrow transplant physicians. The main limitation with these studies has been the reliance on microbiological cultures to characterize the flora. This project will employ a culture-independent technique, 16S ribosomal RNA gene sequencing to address the following aims using pre-clinical models of allogeneic stem cell transplantation (allo-SCT).

    Aims:

    1) Characterize the microbial diversity in the gut during homeostasis and following allo-SCT.

    2) Assess the effect of IL-6 inhibition on the microbiota of the gastrointestinal tract during acute GVHD.

    Outcome & Significance: This project will provide valuable insight into the role of the microbiome during transplantation that may inform of new strategies that could be adopted to protect against unrestrained immune activation and GVHD.

    Suitability: This project would be suitable for Honours students and flexible for clinical students. Undergraduate students looking for placements are encouraged to enquire.

  • Supervisors: Dr Antiopi Varelias (antiopi.varelias@qimrberghofer.edu.au) and Prof Geoff Hill (geoff.hill@qimrberghofer.edu.au)

    Background: IL-6 has been shown to be required for restoring mucosal integrity after intestinal injury however we show that it is detrimental and drives acute GVHD following allo-SCT. Are these contrasting effects of IL-6 regulated by the mode of cytokine receptor signaling? This project will examine the contribution of membrane bound IL-6 receptor signaling (classical) versus soluble IL-6 receptor signaling (trans) to development of GVHD following allogeneic stem cell transplantation (allo-SCT). In the clinical setting, we observed an increase in systemic IL-6 and soluble IL-6R levels in allo-SCT recipients suggesting contribution of the pro-inflammatory IL-6 trans-signaling pathway.

    Moreover, we showed that blockade of the IL-6R with TCZ mAb reduced the incidence of acute GVHD however TCZ mAb inhibits both signaling pathways and hence the responsible signaling pathway cannot be discerned. This project will employ various mouse models of allo-SCT to interrogate the role of IL-6 signaling in mediating GVHD pathogenesis.

    Aims:

    1) Assess the systemic soluble IL-6R and soluble gp130 expression levels in mouse models of allo-SCT.

    2) Delineate the contribution of the IL-6 trans-signaling pathway in the development of GVHD.

    Outcome & Significance: This project will further our understanding of the mechanism by which IL-6 signaling mediates GVHD and may inform of new strategies that could be undertaken to abrogate the development of GVHD.

    Suitability: This project would be suitable for Honours students and flexible for clinical students. Undergraduate students looking for placements are encouraged to enquire.

View all Available Projects

Publications

Journal Article

  • Bunting, Mark D., Varelias, Antiopi, Souza-Fonseca-Guimaraes, Fernando, Schuster, Iona S., Lineburg, Katie E., Kuns, Rachel D., Fleming, Peter, Locke, Kelly R., Huntington, Nicholas D., Blazar, Bruce R., Lane, Steven W., Tey, Siok-Keen, MacDonald, Kelli P. A., Smyth, Mark J., Degli-Esposti, Mariapia A. and Hill, Geoffrey R. (2017) GVHD prevents NK-cell-dependent leukemia and virus-specific innate immunity. Blood, 129 5: 630-642. doi:10.1182/blood-2016-08-734020

  • Varelias, Antiopi, Ormerod, Kate L., Bunting, Mark D., Koyama, Motoko, Gartlan, Kate H., Kuns, Rachel D., Lachner, Nancy, Locke, Kelly R., Lim, Chun Y., Henden, Andrea S., Zhang, Ping, Clouston, Andrew D., Hasnain, Sumaira Z., McGuckin, Michael A., Blazar, Bruce R., MacDonald, Kelli P. A ., Hugenholtz, Philip and Hill, Geoffrey R. (2017) Acute graft-versus-host disease is regulated by an IL-17-sensitive microbiome. Blood, 129 15: 2172-2185. doi:10.1182/blood-2016-08-732628

  • Gartlan, Kate H., Markey, Kate A., Varelias, Antiopi, Bunting, Mark D., Koyama, Motoko, Kuns, Rachel D., Raffelt, Neil C., Olver, Stuart D., Lineburg, Katie E., Cheong, Melody, Teal, Bianca E., Lor, Mary, Comerford, Iain, Teng, Michele W. L., Smyth, Mark J., McCluskey, James, Rossjohn, Jamie, Stockinger, Brigitta, Boyle, Glen M., Lane, Steven W., Clouston, Andrew D., McColl, Shaun R., MacDonald, Kelli P. A. and Hill, Geoffrey R. (2015) Tc17 cells are a proinflammatory, plastic lineage of pathogenic CD8<sup>+</sup> T cells that induce GVHD without antileukemic effects. Blood, 126 13: 1609-1620. doi:10.1182/blood-2015-01-622662

  • Koyama, Motoko, Cheong, Melody, Markey, Kate A., Gartlan, Kate H., Kuns, Rachel D., Locke, Kelly R., Lineburg, Katie E., Teal, Bianca E., Leveque-El Mouttie, Lucie, Bunting, Mark D., Vuckovic, Slavica, Zhang, Ping, Teng, Michele W. L., Varelias, Antiopi, Tey, Siok-Keen, Wockner, Leesa F., Engwerda, Christian R., Smyth, Mark J., Belz, Gabrielle T., McColl, Shaun R., MacDonald, Kelli P. A. and Hill, Geoffrey R. (2015) Donor colonic CD103(+) dendritic cells determine the severity of acute graft-versus-host disease. Journal of Experimental Medicine, 212 8: 1303-1321. doi:10.1084/jem.20150329

  • Alexander K.A., Flynn R., Lineburg K.E., Kuns R.D., Teal B.E., Olver S.D., Lor M., Raffelt N.C., Koyama M., Leveque L., Le Texier L., Melino M., Markey K.A., Varelias A., Engwerda C., Serody J.S., Janela B., Ginhoux F., Clouston A.D., Blazar B.R., Hill G.R. and MacDonald K.P.A. (2014) CSF-1-dependant donor-derived macrophages mediate chronic graft-versus-host disease. Journal of Clinical Investigation, 124 10: 4266-4280. doi:10.1172/JCI75935

  • Zhang, Ping, Tey, Siok-Keen, Koyama, Motoko, Kuns, Rachel D., Olver, Stuart D., Lineburg, Katie E., Lor, Mary, Teal, Bianca E., Raffelt, Neil C., Raju, Jyothy, Leveque, Lucie, Markey, Kate A., Varelias, Antiopi, Clouston, Andrew D., Lane, Steven W., Macdonald, Kelli P. A. and Hill, Geoffrey R. (2013) Induced regulatory T cells promote tolerance when stabilized by rapamycin and IL-2 in vivo. Journal of Immunology, 191 10: 5291-5303. doi:10.4049/jimmunol.1301181

  • Koyama, Motoko, Kuns, Rachel D., Olver, Stuart D., Lineburg, Katie E., Lor, Mary, Teal, Bianca E., Raffelt, Neil C., Leveque, Lucie, Chan, Christopher J., Robb, Renee J., Markey, Kate A., Alexander, Kylie A., Varelias, Antiopi, Clouston, Andrew D., Smyth, Mark J., MacDonald, Kelli P.A. and Hill, Geoffrey R. (2013) Promoting regulation via the inhibition of DNAM-1 after transplantation. Blood, 121 17: 3511-3520. doi:10.1182/blood-2012-07-444026

  • Robb, R.J., Lineburg, K.E., Kuns, R.D., Wilson, Y.A., Raffelt, N.C., Olver, S.D., Varelias, A., Alexander, K.A., Teal, B.E., Sparwasser, T., Hammerling, G.J., Markey, K.A., Koyama, M., Clouston, A.D., Engwerda, C.R., Hill, G.R. and MacDonald, K.P.A. (2012) Identification and expansion of highly suppressive CD8 +FoxP3 + regulatory T cells after experimental allogeneic bone marrow transplantation. Blood, 119 24: 5898-5908. doi:10.1182/blood-2011-12-396119

  • Markey, Kate A., Koyama, Motoko, Kuns, Rachel D., Lineburg, Katie E., Wilson, Yana A., Olver, Stuart D., Raffelt, Neil C., Don, Alistair L. J., Varelias, Antiopi, Robb, Renee J., Cheong, Melody, Engwerda, Christian R., Steptoe, Raymond J., Ramshaw, Hayley S., Lopez, Angel F., Vega-Ramos, Javier, Lew, Andrew M., Villadangos, Jose A., Hill, Geoffrey R. and MacDonald, Kelli P. A. (2012) Immune insufficiency during GVHD is due to defective antigen presentation within dendritic cell subsets. Blood, 119 24: 5918-5930. doi:10.1182/blood-2011-12-398164

  • Koyama, Motoko, Kuns, Rachel D., Olver, Stuart D., Raffelt, Neil C., Wilson, Yana A., Don, Alistair L. J., Lineburg, Katie E., Cheong, Melody, Robb, Renee J., Markey, Kate A., Varelias, Antiopi, Malissen, Bernard, Hammerling, Gunter J., Clouston, Andrew D., Engwerda, Christian R., Bhat, Purnima, MacDonald, Kelli P. A. and Hill, Geoffrey R. (2012) Recipient nonhematopoietic antigen-presenting cells are sufficient to induce lethal acute graft-versus-host disease. Nature Medicine, 18 1: 135-142. doi:10.1038/nm.2597

  • Robb, Renee J., Kreijveld, Ellen, Kuns, Rachel D., Wilson, Yana A., Olver, Stuart D., Don, Alistair L. J., Raffelt, Neil C., De Weerd, Nicole A., Lineburg, Katie E., Varelias, Antiopi, Markey, Kate A., Koyama, Motoko, Clouston, Andrew D., Hertzog, Paul J., MacDonald, Kelli P. A. and Hill, Geoffrey R. (2011) Type I-IFNs control GVHD and GVL responses after transplantation. Blood, 118 12: 3399-3409. doi:10.1182/blood-2010-12-325746

Possible Research Projects

Note for students: The possible research projects listed on this page may not be comprehensive or up to date. Always feel free to contact the staff for more information, and also with your own research ideas.

  • Supervisors: Dr Antiopi Varelias (antiopi.varelias@qimrberghofer.edu.au) and Prof Geoff Hill (geoff.hill@qimrberghofer.edu.au)

    Background: Chemotherapy/radiation treatment during conditioning damages intestinal epithelium resulting in systemic exposure to microbial products normally sequestered in the intestinal lumen, in addition to a marked cytokine release which we have previously published. These microbial products can influence graft-versus-host disease (GVHD) and transplant outcome. Numerous approaches targeting the gut microbiome to harness GVHD (eg. gut decontaminating antibiotics, introduction of beneficial bacteria or targeting anaerobic bacteria) have been attempted with some effect but there is no consensus between bone marrow transplant physicians. The main limitation with these studies has been the reliance on microbiological cultures to characterize the flora. This project will employ a culture-independent technique, 16S ribosomal RNA gene sequencing to address the following aims using pre-clinical models of allogeneic stem cell transplantation (allo-SCT).

    Aims:

    1) Characterize the microbial diversity in the gut during homeostasis and following allo-SCT.

    2) Assess the effect of IL-6 inhibition on the microbiota of the gastrointestinal tract during acute GVHD.

    Outcome & Significance: This project will provide valuable insight into the role of the microbiome during transplantation that may inform of new strategies that could be adopted to protect against unrestrained immune activation and GVHD.

    Suitability: This project would be suitable for Honours students and flexible for clinical students. Undergraduate students looking for placements are encouraged to enquire.

  • Supervisors: Dr Antiopi Varelias (antiopi.varelias@qimrberghofer.edu.au) and Prof Geoff Hill (geoff.hill@qimrberghofer.edu.au)

    Background: IL-6 has been shown to be required for restoring mucosal integrity after intestinal injury however we show that it is detrimental and drives acute GVHD following allo-SCT. Are these contrasting effects of IL-6 regulated by the mode of cytokine receptor signaling? This project will examine the contribution of membrane bound IL-6 receptor signaling (classical) versus soluble IL-6 receptor signaling (trans) to development of GVHD following allogeneic stem cell transplantation (allo-SCT). In the clinical setting, we observed an increase in systemic IL-6 and soluble IL-6R levels in allo-SCT recipients suggesting contribution of the pro-inflammatory IL-6 trans-signaling pathway.

    Moreover, we showed that blockade of the IL-6R with TCZ mAb reduced the incidence of acute GVHD however TCZ mAb inhibits both signaling pathways and hence the responsible signaling pathway cannot be discerned. This project will employ various mouse models of allo-SCT to interrogate the role of IL-6 signaling in mediating GVHD pathogenesis.

    Aims:

    1) Assess the systemic soluble IL-6R and soluble gp130 expression levels in mouse models of allo-SCT.

    2) Delineate the contribution of the IL-6 trans-signaling pathway in the development of GVHD.

    Outcome & Significance: This project will further our understanding of the mechanism by which IL-6 signaling mediates GVHD and may inform of new strategies that could be undertaken to abrogate the development of GVHD.

    Suitability: This project would be suitable for Honours students and flexible for clinical students. Undergraduate students looking for placements are encouraged to enquire.