Dr Antiopi Varelias leads the Transplantation Immunology laboratory at the QIMR Berghofer Medical Research Institute, Brisbane, Australia and is the Coordinator of the Immunology and Infectious diseases seminar series at the Institute. She was awarded her PhD from The University of Adelaide (Faculty of Medicine) in 2002 and held post-doctoral positions within the University of Adelaide’s Department of Surgery (TQEH) and Haematology/Oncology Unit, TQEH before moving to Brisbane to join the Bone Marrow Transplantation laboratory at QIMR Berghofer in 2008, at the time led by Professor Geoff Hill. Under Professor Hill’s mentorship, she has published many original research articles in peer-reviewed high-ranking journals on graft-versus-host disease and has presented her research findings at many international and national scientific meetings. As a chief investigator, she has been the recipient of funding from the NH&MRC and CCQ and is a member of several professional societies (ASTCT, TTS, TSANZ, AAI, ASI, SMI, ICIS).
Dr Varelias’s research interests focus on improving our fundamental understanding of the pathophysiology of graft-versus-host disease using innovative technologies and pre-clinical models, with the view of translating these findings into clinical practice and thereby provide better transplant outcomes for patients. Current research aims to define the immunological basis that underpins graft-versus-host disease, with an emphasis on cellular, cytokine and microbiome interactions that regulate mucosal immunity during stem cell transplantation.
Journal Article: Expansion of IL-17A-secreting CD8 + mucosa-associated invariant T cells in peripheral blood following stem cell mobilization
Varelias, Antiopi, Gartlan, Kate H., Wilkinson, Andrew N., Olver, Stuart D., Samson, Luke D., Tey, Siok-Keen, MacDonald, Kelli P. A. and Hill, Geoffrey R. (2019). Expansion of IL-17A-secreting CD8 + mucosa-associated invariant T cells in peripheral blood following stem cell mobilization. Blood Advances, 3 (5), 718-723. doi: 10.1182/bloodadvances.2018025601
Journal Article: Recipient mucosal-associated invariant T cells control GVHD within the colon
Varelias, Antiopi, Bunting, Mark D., Ormerod, Kate L., Koyama, Motoko, Olver, Stuart D., Straube, Jasmin, Kuns, Rachel D., Robb, Renee J., Henden, Andrea S., Cooper, Leanne, Lachner, Nancy, Gartlan, Kate H., Lantz, Olivier, Kjer-Nielsen, Lars, Mak, Jeffrey Y. W., Fairlie, David P., Clouston, Andrew D., McCluskey, James, Rossjohn, Jamie, Lane, Steven W., Hugenholtz, Philip and Hill, Geoffrey R. (2018). Recipient mucosal-associated invariant T cells control GVHD within the colon. Journal of Clinical Investigation, 128 (5), 1919-1936. doi: 10.1172/JCI91646
Journal Article: Acute graft-versus-host disease is regulated by an IL-17-sensitive microbiome
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
Journal Article: Lung parenchyma-derived IL-6 promotes IL-17A-dependent acute lung injury after allogeneic stem cell transplantation
Varelias, Antiopi, Gartlan, Kate H., Kreijveld, Ellen, Olver, Stuart D., Lor, Mary, Kuns, Rachel D., Lineburg, Katie E., Teal, Bianca E., Raffelt, Neil C., Cheong, Melody, Alexander, Kylie A., Koyama, Motoko, Markey, Kate A., Sturgeon, Elise, Leach, Justine, Reddy, Pavan, Kennedy, Glen A., Yanik, Gregory A., Blazar, Bruce R., Tey, Siok-Keen, Clouston, Andrew D., MacDonald, Kelli P. A., Cooke, Kenneth R. and Hill, Geoffrey R. (2015). Lung parenchyma-derived IL-6 promotes IL-17A-dependent acute lung injury after allogeneic stem cell transplantation. Blood, 125 (15), 2435-2444. doi: 10.1182/blood-2014-07-590232
Kennedy, Glen A., Varelias, Antiopi, Vuckovic, Slavica, Le Texier, Laetitia, Gartlan, Kate H., Zhang, Ping, Thomas, Gethin, Anderson, Lisa, Boyle, Glen, Cloonan, Nicole, Leach, Justine, Sturgeon, Elise, Avery, Judy, Olver, Stuart D., Lor, Mary, Misra, Ashish K., Hutchins, Cheryl, Morton, A. James, Durrant, Simon T. S., Subramoniapillai, Elango, Butler, Jason P., Curley, Cameron I., MacDonald, Kelli P. A., Tey, Siok-Keen and Hill, Geoffrey R. (2014). Addition of interleukin-6 inhibition with tocilizumab to standard graft-versus-host disease prophylaxis after allogeneic stem-cell transplantation: a phase 1/2 trial. The Lancet Oncology, 15 (13), 1451-1459. doi: 10.1016/S1470-2045(14)71017-4
Defining the critical determinants of viral-mediated pneumonitis after bone marrow transplantation.
Doctor Philosophy
Classification and functional characterisation of the murine gut bacterial family Muribaculaceae
(2021) Doctor Philosophy
Modulating Donor T Cell Polarisation After Bone Marrow Transplantation to Prevent Graft-Versus-Host Disease
Doctor Philosophy
Background
Viral infection and reactivation following stem cell transplantation (SCT) is a common complication following this procedure, which is performed for the treatment of blood cancers. One such pathogen is respiratory syncytial virus (RSV), a common community-acquired infection that leads to significant morbidity in immunocompromised SCT patients. Current treatment strategies for patients infected with RSV is the use of anti-viral agents however these are ineffective. Thus, this complication remains a significant clinical problem where new treatments are desperately needed. To address this, a better understanding of the immunological mechanisms that underlie this disease are essential.
Aims
The specific aim of this project is to establish a robust model of RSV infection in the stem cell transplant setting using Pneumonia Virus of Mice (PVM), the murine relative of RSV. This will enable the contribution of host innate and acquired mucosal immune responses to the viral infection to be dissected.
Approaches / Techniques to be utilised
This project is not limited to, but will involve, extensive animal work, flow cytometry, immunological assays, molecular and viral techniques.
This project is suitable for Honours, Masters and PhD students. Please contact Dr Varelias (antiopi.varelias@qimrberghofer.edu.au) for further details.
Background
To date, stem cell transplantation (SCT) remains the preferred treatment option for the majority of blood cancers. Chemotherapy/radiation 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. We have demonstrated that these microbial products and cytokines modulate graft-versus-host disease (GVHD) and thereby transplant outcome. Numerous approaches in the clinic targeting intestinal microbiota to harness GVHD such as gut decontaminating antibiotics, introduction of beneficial bacteria or targeting anaerobic bacteria have been attempted but these have shown varied effects. A greater understanding of the cellular and molecular mechanisms underlying these approaches will inform of new strategies that could be adopted to protect against unrestrained immune activation and GVHD. Recently, we demonstrated that mucosal associated invariant T (MAIT) cells, activated in response to engagement with microbial-derived riboflavin derivatives loaded onto MR1 ligands, protected against intestinal acute GVHD.
Aims
The overall aim of this project is to further investigate the host innate immune response and its interaction with intestinal microbiota during homeostasis and in acute GVHD.
Approaches / Techniques to be utilised
This project is not limited to, but will involve, extensive animal work, flow cytometry, immunological assays, molecular and microbiological techniques.
This project is suitable for Honours, Masters and PhD students. Please contact Dr Varelias (antiopi.varelias@qimrberghofer.edu.au) for further details.
Varelias, Antiopi, Gartlan, Kate H., Wilkinson, Andrew N., Olver, Stuart D., Samson, Luke D., Tey, Siok-Keen, MacDonald, Kelli P. A. and Hill, Geoffrey R. (2019). Expansion of IL-17A-secreting CD8 + mucosa-associated invariant T cells in peripheral blood following stem cell mobilization. Blood Advances, 3 (5), 718-723. doi: 10.1182/bloodadvances.2018025601
Recipient mucosal-associated invariant T cells control GVHD within the colon
Varelias, Antiopi, Bunting, Mark D., Ormerod, Kate L., Koyama, Motoko, Olver, Stuart D., Straube, Jasmin, Kuns, Rachel D., Robb, Renee J., Henden, Andrea S., Cooper, Leanne, Lachner, Nancy, Gartlan, Kate H., Lantz, Olivier, Kjer-Nielsen, Lars, Mak, Jeffrey Y. W., Fairlie, David P., Clouston, Andrew D., McCluskey, James, Rossjohn, Jamie, Lane, Steven W., Hugenholtz, Philip and Hill, Geoffrey R. (2018). Recipient mucosal-associated invariant T cells control GVHD within the colon. Journal of Clinical Investigation, 128 (5), 1919-1936. doi: 10.1172/JCI91646
Acute graft-versus-host disease is regulated by an IL-17-sensitive microbiome
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
Varelias, Antiopi, Gartlan, Kate H., Kreijveld, Ellen, Olver, Stuart D., Lor, Mary, Kuns, Rachel D., Lineburg, Katie E., Teal, Bianca E., Raffelt, Neil C., Cheong, Melody, Alexander, Kylie A., Koyama, Motoko, Markey, Kate A., Sturgeon, Elise, Leach, Justine, Reddy, Pavan, Kennedy, Glen A., Yanik, Gregory A., Blazar, Bruce R., Tey, Siok-Keen, Clouston, Andrew D., MacDonald, Kelli P. A., Cooke, Kenneth R. and Hill, Geoffrey R. (2015). Lung parenchyma-derived IL-6 promotes IL-17A-dependent acute lung injury after allogeneic stem cell transplantation. Blood, 125 (15), 2435-2444. doi: 10.1182/blood-2014-07-590232
Kennedy, Glen A., Varelias, Antiopi, Vuckovic, Slavica, Le Texier, Laetitia, Gartlan, Kate H., Zhang, Ping, Thomas, Gethin, Anderson, Lisa, Boyle, Glen, Cloonan, Nicole, Leach, Justine, Sturgeon, Elise, Avery, Judy, Olver, Stuart D., Lor, Mary, Misra, Ashish K., Hutchins, Cheryl, Morton, A. James, Durrant, Simon T. S., Subramoniapillai, Elango, Butler, Jason P., Curley, Cameron I., MacDonald, Kelli P. A., Tey, Siok-Keen and Hill, Geoffrey R. (2014). Addition of interleukin-6 inhibition with tocilizumab to standard graft-versus-host disease prophylaxis after allogeneic stem-cell transplantation: a phase 1/2 trial. The Lancet Oncology, 15 (13), 1451-1459. doi: 10.1016/S1470-2045(14)71017-4
Wang, Yewei, Ullah, Md Ashik, Waltner, Olivia G., Bhise, Shruti S., Ensbey, Kathleen S., Schmidt, Christine R., Legg, Samuel R.W., Sekiguchi, Tomoko, Nelson, Ethan L., Kuns, Rachel D., Nemychenkov, Nicole S., Atilla, Erden, Yeh, Albert C., Takahashi, Shuichiro, Boiko, Julie R., Varelias, Antiopi, Blazar, Bruce R., Koyama, Motoko, Minnie, Simone A., Clouston, Andrew D., Furlan, Scott N., Zhang, Ping and Hill, Geoffrey R. (2024). Calcineurin inhibition rescues alloantigen-specific central memory T cell subsets that promote chronic GVHD. Journal of Clinical Investigation, 134 (11) e170125. doi: 10.1172/jci170125
Zhang, Ping, Fleming, Peter, Andoniou, Christopher E., Waltner, Olivia G., Bhise, Shruti S., Martins, Jose Paulo, McEnroe, Benjamin A., Voigt, Valentina, Daly, Sheridan, Kuns, Rachel D., Ekwe, Adaeze P., Henden, Andrea S., Saldan, Alda, Olver, Stuart, Varelias, Antiopi, Smith, Corey, Schmidt, Christine R., Ensbey, Kathleen S., Legg, Samuel R.W., Sekiguchi, Tomoko, Minnie, Simone A., Gradwell, Mark, Wagenaar, Irma, Clouston, Andrew D., Koyama, Motoko, Furlan, Scott N., Kennedy, Glen A., Ward, E Sally, Degli-Esposti, Mariapia A. ... Tey, Siok-Keen (2024). IL-6–mediated endothelial injury impairs antiviral humoral immunity after bone marrow transplantation. Journal of Clinical Investigation, 134 (7) e174184. doi: 10.1172/jci174184
Takahashi, Shuichiro, Minnie, Simone A., Ensbey, Kathleen S., Schmidt, Christine R., Sekiguchi, Tomoko, Legg, Samuel R. W., Zhang, Ping, Koyama, Motoko, Olver, Stuart D., Collinge, Alika D., Keshmiri, Sara, Comstock, Melissa L., Varelias, Antiopi, Green, Damian J. and Hill, Geoffrey R. (2024). Regulatory T cells suppress myeloma-specific immunity during autologous stem cell mobilization and transplantation. Blood, 143 (16), 1656-1669. doi: 10.1182/blood.2023022000
Intestinal microbiota controls graft-versus-host disease independent of donor-host genetic disparity
Koyama, Motoko, Hippe, Daniel S., Srinivasan, Sujatha, Proll, Sean C., Miltiadous, Oriana, Li, Naisi, Zhang, Ping, Ensbey, Kathleen S., Hoffman, Noah G., Schmidt, Christine R., Yeh, Albert C., Minnie, Simone A., Strenk, Susan M., Fiedler, Tina L., Hattangady, Namita, Kowalsky, Jacob, Grady, Willian M., Degli-Esposti, Mariapia A., Varelias, Antiopi, Clouston, Andrew D., van den Brink, Marcel R.M., Dey, Neelendu, Randolph, Timothy W., Markey, Kate A., Fredricks, David N. and Hill, Geoffrey R. (2023). Intestinal microbiota controls graft-versus-host disease independent of donor-host genetic disparity. Immunity, 56 (8), 1876-1893.e8. doi: 10.1016/j.immuni.2023.06.024
Minnie, Simone A., Waltner, Olivia G., Ensbey, Kathleen S., Olver, Stuart D., Collinge, Alika D., Sester, David P., Schmidt, Christine R., Legg, Samuel R.W., Takahashi, Shuichiro, Nemychenkov, Nicole S., Sekiguchi, Tomoko, Driessens, Gregory, Zhang, Ping, Koyama, Motoko, Spencer, Andrew, Holmberg, Leona A., Furlan, Scott N., Varelias, Antiopi and Hill, Geoffrey R. (2022). TIGIT inhibition and lenalidomide synergistically promote anti-myeloma immune responses after stem cell transplantation in mice. Journal of Clinical Investigation, 133 (4) e157907, 1-11. doi: 10.1172/jci157907
Editorial: Mouse Models of Hematopoietic Stem Cell Transplantation
Varelias, Antiopi, Zhang, Ping and Hashimoto, Daigo (2022). Editorial: Mouse Models of Hematopoietic Stem Cell Transplantation. Frontiers in Immunology, 13 882592, 1-2. doi: 10.3389/fimmu.2022.882592
Oyong, Damian. A., Loughland, Jessica. R., Soon, Megan. S.F., Chan, Jo-Anne, Andrew, Dean, Wines, Bruce D., Hogarth, P. Mark, Olver, Stuart D., Collinge, Alika D., Varelias, Antiopi, Beeson, James G., Kenangalem, Enny, Price, Ric N., Anstey, Nicholas M., Minigo, Gabriela and Boyle, Michelle J. (2022). Adults with Plasmodium falciparum malaria have higher magnitude and quality of circulating T-follicular helper cells compared to children. eBioMedicine, 75 103784, 1-22. doi: 10.1016/j.ebiom.2021.103784
Yeh, Albert C., Varelias, Antiopi, Reddy, Anupama, Barone, Sierra M., Olver, Stuart D., Chilson, Kate, Onstad, Lynn E., Ensbey, Kathleen S., Henden, Andrea S, Samson, Luke, Jaeger, Carla A, Bi, Timothy, Dahlman, Kimberly B., Kim, Tae Kon, Zhang, Ping, Degli-Esposti, Mariapia A., Newell, Evan W., Jagasia, Madan H., Irish, Jonathan M., Lee, Stephanie J. and Hill, Geoffrey R. (2021). CMV exposure drives long-term CD57+ CD4 memory T-cell inflation following allogeneic stem cell transplant. Blood, 138 (26), 2874-2885. doi: 10.1182/blood.2020009492
IFN-λ therapy prevents severe gastrointestinal graft-versus-host disease
Henden, Andrea S., Koyama, Motoko, Robb, Renee J., Forero, Adriana, Kuns, Rachel D., Chang, Karshing, Ensbey, Kathleen S., Varelias, Antiopi, Kazakoff, Stephen H., Waddell, Nicole, Clouston, Andrew D., Giri, Rabina, Begun, Jakob, Blazar, Bruce R., Degli-Esposti, Mariapia A., Kotenko, Sergei V., Lane, Steven W., Bowerman, Kate L., Savan, Ram, Hugenholtz, Philip, Gartlan, Kate H. and Hill, Geoffrey R. (2021). IFN-λ therapy prevents severe gastrointestinal graft-versus-host disease. Blood, 138 (8), 722-737. doi: 10.1182/blood.2020006375
Kennedy, Glen, Tey, Siok-Keen, Buizen, Luke, Varelias, Antiopi, Gartlan, Kate H., Curley, Cameron, Olver, Stuart, Chang, Karshing, Butler, Jason, Misra, Ashish, Subramoniapillai, Elango, Morton, Anthony, Durrant, Simon, Henden, Andrea S, Moore, John, Ritchie, David S, Gottlieb, David, Cooney, Julian P, Paul, Sanjoy K and Hill, Geoffrey R. (2021). A phase 3 double-blind study of the addition of tocilizumab versus placebo to cyclosporin/methotrexate GvHD prophylaxis. Blood, 137 (14), 1970-1979. doi: 10.1182/blood.2020009050
Engel, Jessica A., Lee, Hyun Jae, Williams, Cameron G., Kuns, Rachel, Olver, Stuart, Lansink, Lianne Im, Soon, Megan Sf, Andersen, Stacey B., Powell, Joseph E., Svensson, Valentine, Teichmann, Sarah A., Hill, Geoffrey R., Varelias, Antiopi, Koyama, Motoko and Haque, Ashraful (2020). Single-cell transcriptomics of alloreactive CD4+ T cells over time reveals divergent fates during gut graft-versus-host disease. JCI Insight, 5 (13) 137990. doi: 10.1172/jci.insight.137990
ASC modulates CTL cytotoxicity and transplant outcome independent of the inflammasome
Cheong, Melody, Gartlan, Kate H., Lee, Jason S., Tey, Siok-Keen, Zhang, Ping, Kuns, Rachel D., Andoniou, Christopher E., Martins, Jose Paulo, Chang, Karshing, Sutton, Vivien R., Kelly, Greg, Varelias, Antiopi, Vuckovic, Slavica, Markey, Kate A., Boyle, Glen M., Smyth, Mark J., Engwerda, Christian R., MacDonald, Kelli P.A., Trapani, Joseph A., Degli-Esposti, Mariapia A., Koyama, Motoko and Hill, Geoffrey R. (2020). ASC modulates CTL cytotoxicity and transplant outcome independent of the inflammasome. Cancer Immunology Research, 8 (8), 1085-1098. doi: 10.1158/2326-6066.cir-19-0653
PAG1 limits allergen-induced type 2 inflammation in the murine lung
Ullah, Md Ashik, Vicente, Cristina T., Collinson, Natasha, Curren, Bodie, Sikder, Md Al Amin, Sebina, Ismail, Simpson, Jennifer, Varelias, Antiopi, Lindquist, Jonathan A., Ferreira, Manuel A. R. and Phipps, Simon (2020). PAG1 limits allergen-induced type 2 inflammation in the murine lung. Allergy, 75 (2) all.13991, 336-345. doi: 10.1111/all.13991
Bowerman, Kate L., Varelias, Antiopi, Lachner, Nancy, Kuns, Rachel D., Hill, Geoffrey R. and Hugenholtz, Philip (2020). Continuous pre- and post-transplant exposure to a disease-associated gut microbiome promotes hyper-acute graft-versus-host disease in wild-type mice. Gut Microbes, 11 (4), 1-17. doi: 10.1080/19490976.2019.1705729
MAIT cells promote tumor initiation, growth and metastases via tumor MR1
Yan, Juming, Allen, Stacey, McDonald, Elizabeth, Das, Indrajit, Mak, Jeffrey Y. W., Liu, Ligong, Fairlie, David P., Meehan, Bronwyn S., Chen, Zhenjun, Corbett, Alexandra J., Varelias, Antiopi, Smyth, Mark J. and Teng, Michele W. L. (2020). MAIT cells promote tumor initiation, growth and metastases via tumor MR1. Cancer Discovery, 10 (1), 124-141. doi: 10.1158/2159-8290.cd-19-0569
Koyama, Motoko, Mukhopadhyay, Pamela, Schuster, Iona S., Henden, Andrea S., Hülsdünker, Jan, Varelias, Antiopi, Vetizou, Marie, Kuns, Rachel D., Robb, Renee J., Zhang, Ping, Blazar, Bruce B., Thomas, Ranjeny, Begun, Jakob, Waddell, Nicola, Trinchieri, Giorgio, Zeiser, Robert, Clouston, Andrew D., Degli-Esposti, Mariapia A. and Hill, Geoffrey R. (2019). MHC class II antigen presentation by the intestinal epithelium initiates graft-versus-host disease and is influenced by the microbiota. Immunity, 51 (5), 885-898. doi: 10.1016/j.immuni.2019.08.011
Andersen, Sarah, Staudacher, Heidi, Weber, Nicholas, Kennedy, Glen, Varelias, Antiopi, Banks, Merrilyn and Bauer, Judy (2019). Pilot study investigating the effect of enteral and parenteral nutrition on the gastrointestinal microbiome post‐allogeneic transplantation. British Journal of Haematology, 188 (4) bjh.16218, 570-581. doi: 10.1111/bjh.16218
Wilkinson, Andrew N., Chang, Karshing, Kuns, Rachel D., Henden, Andrea S., Minnie, Simone A., Ensbey, Kathleen S., Clouston, Andrew D., Zhang, Ping, Koyama, Motoko, Hidalgo, Juan, Rose-John, Stefan, Varelias, Antiopi, Vuckovic, Slavica, Gartlan, Kate H. and Hill, Geoffrey R. (2019). IL-6 dysregulation originates in dendritic cells and initiates graft-versus-host disease via classical signaling. Blood, 134 (23), 2092-2106. doi: 10.1182/blood.2019000396
Varelias, Antiopi, Gartlan, Kate H., Wilkinson, Andrew N., Olver, Stuart D., Samson, Luke D., Tey, Siok-Keen, MacDonald, Kelli P. A. and Hill, Geoffrey R. (2019). Expansion of IL-17A-secreting CD8 + mucosa-associated invariant T cells in peripheral blood following stem cell mobilization. Blood Advances, 3 (5), 718-723. doi: 10.1182/bloodadvances.2018025601
Zhang, Ping, Raju, Jyothy, Ullah, Md Ashik, Au, Raymond, Varelias, Antiopi, Gartlan, Kate H, Olver, Stuart D., Samson, Luke D., Sturgeon, Elise, Zomerdijk, Nienke, Avery, Judy, Gargett, Tessa, Brown, Michael P., Coin, Lachlan J., Ganesamoorthy, Devika, Hutchins, Cheryl, Pratt, Gary R, Kennedy, Glen A., Morton, A. James, Curley, Cameron I., Hill, Geoffrey R. and Tey, Siok-Keen (2019). Phase I trial of inducible caspase 9 T cells in adult stem cell transplant demonstrates massive clonotypic proliferative potential and long-term persistence of transgenic T cells. Clinical Cancer Research, 25 (6), 1749-1755. doi: 10.1158/1078-0432.CCR-18-3069
Bone marrow transplantation generates T cell–dependent control of myeloma in mice
Vuckovic, Slavica, Minnie, Simone A., Smith, David, Gartlan, Kate H., Watkins, Thomas S., Markey, Kate A., Mukhopadhyay, Pamela, Guillerey, Camille, Kuns, Rachel D., Locke, Kelly R., Pritchard, Antonia L., Johansson, Peter A., Varelias, Antiopi, Zhang, Ping, Huntington, Nicholas D., Waddell, Nicola, Chesi, Marta, Miles, John J., Smyth, Mark J. and Hill, Geoffrey R. (2018). Bone marrow transplantation generates T cell–dependent control of myeloma in mice. Journal of Clinical Investigation, 129 (1) CI98888, 106-121. doi: 10.1172/jci98888
Recipient mucosal-associated invariant T cells control GVHD within the colon
Varelias, Antiopi, Bunting, Mark D., Ormerod, Kate L., Koyama, Motoko, Olver, Stuart D., Straube, Jasmin, Kuns, Rachel D., Robb, Renee J., Henden, Andrea S., Cooper, Leanne, Lachner, Nancy, Gartlan, Kate H., Lantz, Olivier, Kjer-Nielsen, Lars, Mak, Jeffrey Y. W., Fairlie, David P., Clouston, Andrew D., McCluskey, James, Rossjohn, Jamie, Lane, Steven W., Hugenholtz, Philip and Hill, Geoffrey R. (2018). Recipient mucosal-associated invariant T cells control GVHD within the colon. Journal of Clinical Investigation, 128 (5), 1919-1936. doi: 10.1172/JCI91646
Catchpoole, Elizabeth M., Thirunavukarasu, Caitlin E., Varelias, Antiopi, Schlebusch, Sanmarié, Olver, Stuart, Zomerdijk, Nienke, Osland, Emma, Kennedy, Glen A., Tey, Siok-Keen, Hill, Geoffrey R. and Markey, Kate A. (2018). Early blood stream infection after BMT is associated with cytokine dysregulation and poor overall survival. Biology of Blood and Marrow Transplantation, 24 (7), 1360-1366. doi: 10.1016/j.bbmt.2018.02.025
A critical role for donor-derived IL-22 in cutaneous chronic GVHD
Gartlan, Kate H., Bommiasamy, Hemamalini, Paz, Katelyn, Wilkinson, Andrew N., Owen, Mary, Reichenbach, Dawn K., Banovic, Tatjana, Wehner, Kimberly, Buchanan, Faith, Varelias, Antiopi, Kuns, Rachel D., Chang, Karshing, Fedoriw, Yuri, Shea, Thomas, Coghill, James, Zaiken, Michael, Plank, Maximilian W., Foster, Paul S., Clouston, Andrew D., Blazar, Bruce R., Serody, Jonathan S. and Hill, Geoffrey R. (2017). A critical role for donor-derived IL-22 in cutaneous chronic GVHD. American Journal of Transplantation , 18 (4), 810-820. doi: 10.1111/ajt.14513
Eomesodermin promotes the development of Type-1 Regulatory T (TR1) cells
Zhang, Ping, Lee, Jason S., Gartlan, Kate H., Schuster, Iona S., Comerford, Iain, Varelias, Antiopi, Ullah, Md Ashik, Vuckovic, Slavica, Koyama, Motoko, Kuns, Rachel D., Locke, Kelly R., Beckett, Kirrilee J., Olver, Stuart D., Samson, Luke D., Montes de Oca, Marcela, de Labastida Rivera, Fabian, Clouston, Andrew D., Belz, Gabrielle T., Blazar, Bruce R., MacDonald, Kelli P., McColl, Shaun R., Thomas, Ranjeny, Engwerda, Christian R., Degli-Esposti, Mariapia A., Kallies, Axel, Tey, Siok-Keen and Hill, Geoffrey R. (2017). Eomesodermin promotes the development of Type-1 Regulatory T (TR1) cells. Science Immunology, 2 (10) eaah7152. doi: 10.1126/sciimmunol.aah7152
Gartlan, Kate H., Varelias, Antiopi, Koyama, Motoko, Robb, Renee J., Markey, Kate A., Chang, Karshing, Wilkinson, Andrew N., Smith, David, Ullah, Md Ashik, Kuns, Rachel D., Raffelt, Neil C., Olver, Stuart D., Lineburg, Katie E., Teal, Bianca E., Cheong, Melody, Teng, Michele W. L., Smyth, Mark J., Tey, Siok-Keen, MacDonald, Kelli P. A. and Hill, Geoffrey R. (2017). Th17 plasticity and transition toward a pathogenic cytokine signature are regulated by cyclosporine after allogeneic SCT. Blood Advances, 1 (6), 341-351. doi: 10.1182/bloodadvances.2016002980
GVHD prevents NK-cell-dependent leukemia and virus-specific innate immunity
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
Acute graft-versus-host disease is regulated by an IL-17-sensitive microbiome
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
Tey, S-K., Vuckovic, S., Varelias, A., Martins, J. P., Olver, S., Samson, L., Sturgeon, E., Leach, J., Avery, J., Nakagaki, M., Butler, J. P., Curley, C., Morton, A. J., Durrant, S. T., Kennedy, G. A. and Hill, G. R. (2016). Pharmacokinetics and immunological outcomes of alemtuzumab-based treatment for steroid-refractory acute GvHD. Bone Marrow Transplantation, 51 (8), 1153-1155. doi: 10.1038/bmt.2016.83
Sheel, Meru, Beattie, Lynette, Frame, Teija C. M., Rivera, Fabian de Labastida, Faleiro, Rebecca J., Bunn, Patrick T., de Oca, Marcela Montes, Edwards, Chelsea L., Ng, Susanna S., Kumar, Rajiv, Amante, Fiona H., Best, Shannon E., McColl, Shaun R., Varelias, Antiopi, Kuns, Rachel D., MacDonald, Kelli P. A., Smyth, Mark J., Haque, Ashraful, Hill, Geoff R. and Engwerda, Christian R. (2015). IL-17A-Producing gamma delta T Cells Suppress Early Control of Parasite Growth by Monocytes in the Liver. Journal of Immunology, 195 (12), 5707-5717. doi: 10.4049/jimmunol.1501046
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+ T cells that induce GVHD without antileukemic effects. Blood, 126 (13), 1609-1620. doi: 10.1182/blood-2015-01-622662
Donor colonic CD103(+) dendritic cells determine the severity of acute graft-versus-host disease
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
Varelias, Antiopi, Gartlan, Kate H., Kreijveld, Ellen, Olver, Stuart D., Lor, Mary, Kuns, Rachel D., Lineburg, Katie E., Teal, Bianca E., Raffelt, Neil C., Cheong, Melody, Alexander, Kylie A., Koyama, Motoko, Markey, Kate A., Sturgeon, Elise, Leach, Justine, Reddy, Pavan, Kennedy, Glen A., Yanik, Gregory A., Blazar, Bruce R., Tey, Siok-Keen, Clouston, Andrew D., MacDonald, Kelli P. A., Cooke, Kenneth R. and Hill, Geoffrey R. (2015). Lung parenchyma-derived IL-6 promotes IL-17A-dependent acute lung injury after allogeneic stem cell transplantation. Blood, 125 (15), 2435-2444. doi: 10.1182/blood-2014-07-590232
Ullah, Md Ashik, Revez, Joana A., Loh, Zhixuan, Simpson, Jennifer, Zhang, Vivian, Bain, Lisa, Varelias, Antiopi, Rose-John, Stefan, Blumenthal, Antje, Smyth, Mark J., Hill, Geoffrey R., Sukkar, Manuel A. R, Ferreira M. A. R. and Phipps, Simon (2015). Allergen-induced IL-6 trans-signaling activates γδ T cells to promote type 2 and type 17 airway inflammation. Journal of Allergy and Clinical Immunology, 136 (4), 1065-1073. doi: 10.1016/j.jaci.2015.02.032
Kennedy, Glen A., Varelias, Antiopi, Vuckovic, Slavica, Le Texier, Laetitia, Gartlan, Kate H., Zhang, Ping, Thomas, Gethin, Anderson, Lisa, Boyle, Glen, Cloonan, Nicole, Leach, Justine, Sturgeon, Elise, Avery, Judy, Olver, Stuart D., Lor, Mary, Misra, Ashish K., Hutchins, Cheryl, Morton, A. James, Durrant, Simon T. S., Subramoniapillai, Elango, Butler, Jason P., Curley, Cameron I., MacDonald, Kelli P. A., Tey, Siok-Keen and Hill, Geoffrey R. (2014). Addition of interleukin-6 inhibition with tocilizumab to standard graft-versus-host disease prophylaxis after allogeneic stem-cell transplantation: a phase 1/2 trial. The Lancet Oncology, 15 (13), 1451-1459. doi: 10.1016/S1470-2045(14)71017-4
CSF-1-dependant donor-derived macrophages mediate chronic graft-versus-host disease
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
Type I IFN signaling in CD8-DCs impairs Th1-dependent malaria immunity
Haque, Ashraful, Best, Shannon E., De Oca, Marcela Montes, James, Kylie R., Ammerdorffer, Anne, Edwards, Chelsea L., De Labastida Rivera, Fabian, Amante, Fiona H., Bunn, Patrick T., Sheel, Meru, Sebina, Ismail, Koyama, Motoko, Varelias, Antiopi, Hertzog, Paul J., Kalinke, Ulrich, Gun, Sin Yee, Renia, Laurent, Ruedl, Christiane, MacDonald, Kelli P.A., Hill, Geoffrey R. and Engwerda, Christian R. (2014). Type I IFN signaling in CD8-DCs impairs Th1-dependent malaria immunity. Journal of Clinical Investigation, 124 (6), 2483-2496. doi: 10.1172/JCI70698
Induced regulatory T cells promote tolerance when stabilized by rapamycin and IL-2 in vivo
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
Promoting regulation via the inhibition of DNAM-1 after transplantation
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
Type I-IFNs control GVHD and GVL responses after transplantation
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
Stem cell mobilization with G-CSF induces type 17 differentiation and promotes scleroderma
Hill, Geoffrey R., Olver, Stuart D., Kuns, Rachel D., Varelias, Antiopi, Raffelt, Neil C., Don, Alistair L., Markey, Kate A., Wilson, Yana A., Smyth, Mark J., Iwakura, Yoichiro, Tocker, Joel, Clouston, Andrew D. and MacDonald, Kelli P. A. (2010). Stem cell mobilization with G-CSF induces type 17 differentiation and promotes scleroderma. Blood, 116 (5), 819-828. doi: 10.1182/blood-2009-11-256495
Defining the critical determinants of viral-mediated pneumonitis after bone marrow transplantation.
Doctor Philosophy — Principal Advisor
Other advisors:
Modulating Donor T Cell Polarisation After Bone Marrow Transplantation to Prevent Graft-Versus-Host Disease
Doctor Philosophy — Associate Advisor
Other advisors:
Classification and functional characterisation of the murine gut bacterial family Muribaculaceae
(2021) Doctor Philosophy — Associate Advisor
Other advisors:
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.
Background
Viral infection and reactivation following stem cell transplantation (SCT) is a common complication following this procedure, which is performed for the treatment of blood cancers. One such pathogen is respiratory syncytial virus (RSV), a common community-acquired infection that leads to significant morbidity in immunocompromised SCT patients. Current treatment strategies for patients infected with RSV is the use of anti-viral agents however these are ineffective. Thus, this complication remains a significant clinical problem where new treatments are desperately needed. To address this, a better understanding of the immunological mechanisms that underlie this disease are essential.
Aims
The specific aim of this project is to establish a robust model of RSV infection in the stem cell transplant setting using Pneumonia Virus of Mice (PVM), the murine relative of RSV. This will enable the contribution of host innate and acquired mucosal immune responses to the viral infection to be dissected.
Approaches / Techniques to be utilised
This project is not limited to, but will involve, extensive animal work, flow cytometry, immunological assays, molecular and viral techniques.
This project is suitable for Honours, Masters and PhD students. Please contact Dr Varelias (antiopi.varelias@qimrberghofer.edu.au) for further details.
Background
To date, stem cell transplantation (SCT) remains the preferred treatment option for the majority of blood cancers. Chemotherapy/radiation 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. We have demonstrated that these microbial products and cytokines modulate graft-versus-host disease (GVHD) and thereby transplant outcome. Numerous approaches in the clinic targeting intestinal microbiota to harness GVHD such as gut decontaminating antibiotics, introduction of beneficial bacteria or targeting anaerobic bacteria have been attempted but these have shown varied effects. A greater understanding of the cellular and molecular mechanisms underlying these approaches will inform of new strategies that could be adopted to protect against unrestrained immune activation and GVHD. Recently, we demonstrated that mucosal associated invariant T (MAIT) cells, activated in response to engagement with microbial-derived riboflavin derivatives loaded onto MR1 ligands, protected against intestinal acute GVHD.
Aims
The overall aim of this project is to further investigate the host innate immune response and its interaction with intestinal microbiota during homeostasis and in acute GVHD.
Approaches / Techniques to be utilised
This project is not limited to, but will involve, extensive animal work, flow cytometry, immunological assays, molecular and microbiological techniques.
This project is suitable for Honours, Masters and PhD students. Please contact Dr Varelias (antiopi.varelias@qimrberghofer.edu.au) for further details.