Dr Kate Gartlan is an immunologist with considerable expertise in cellular immunology, particularly using in vivo models of inflammation to investigate immune-modulation and T cell polarisation. Dr Gartlan began her research career at WEHI within Professor Ken Shortman’s laboratory developing strong skills in both molecular and cell biology, where she became interested in the early factors that influence adaptive immunity. She completed her PhD in 2009 at the Burnet Institute working with Associate Professor Mark Wright, where she studied functional redundancy between Tetraspanin proteins in the immune system. To advance her understanding of inflammatory mediators and adaptive immune polarisation, she moved to the University of Oxford and took up a postdoctoral position within the Sir William Dunn School of Pathology. Working with Professor Quentin Sattentau, she investigated novel ways to modulate T cell polarisation and influence B cell responses to HIV vaccines.
After returning to Australia, she has worked with Professor Geoff Hill at QIMR Berghofer investigating novel therapies to treat graft-versus-host disease (GVHD) in allograft recipients. Dr Gartlan has held active teaching roles within both university and research institute environments, contributing to undergraduate science and medicine programs at both departmental and college levels.
Her main research interests at present surround the role of IL-17 & IL-22 in GVHD, potential therapeutics to modulate T cell polarisation after allogeneic bone marrow/stem cell transplant (BMT/SCT), as well as developing novel inhibitors of graft rejection to improve engraftment after BMT/SCT.
Journal Article: Donor T-cell–derived GM-CSF drives alloantigen presentation by dendritic cells in the gastrointestinal tract
Gartlan, Kate H., Koyama, Motoko, Lineburg, Katie E., Chang, Karshing, Ensbey, Kathleen S., Kuns, Rachel D., Henden, Andrea S., Samson, Luke D., Clouston, Andrew D., Lopez, Angel F., MacDonald, Kelli P. A. and Hill, Geoffrey R. (2019). Donor T-cell–derived GM-CSF drives alloantigen presentation by dendritic cells in the gastrointestinal tract. Blood Advances, 3 (19), 2859-2865. doi: 10.1182/bloodadvances.2019000053
Journal Article: IL-6 dysregulation originates in dendritic cells and initiates graft-versus-host disease via classical signaling
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
Journal Article: 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
Journal Article: Tc17 cells are a proinflammatory, plastic lineage of pathogenic CD8<sup>+</sup> T cells that induce GVHD without antileukemic effects
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
Modulating Donor T Cell Polarisation After Bone Marrow Transplantation to Prevent Graft-Versus-Host Disease
Doctor Philosophy
Anti-leukaemia effect of Interferons
(2019) Doctor Philosophy
Understanding the role of IL-6 signalling in Graft-Versus-Host Disease (GVHD)
(2019) Doctor Philosophy
What is the influence of infection driven T cell polarisation on graft-versus-host disease?
Background: Stem cell/bone marrow transplantation (SCT/BMT) is an important curative therapy for haematological malignancies and disorders; however graft-versus-host disease (GVHD) and infection are two major complications of this procedure. Whilst it is well established that viral and bacterial infections influence GVHD pathogenesis, the impact of fungal infection after transplant is poorly understood. In non-transplant settings, adaptive immune responses to fungal infections are commonly associated with IL-17 production by T cells that enhance anti-fungal immunity. However our laboratory and others have demonstrated that the IL-17 differentiation pathway is pathogenic in the context of allotransplantation. We are offering a project designed to understand the relationship between fungal infection and GVHD outcomes.
Aims: This project aims to 1) establish an in vivo infection model that can be used in conjunction with bone marrow transplant in pre-clinical experimental systems. 2) Explore the relationship between fungal infection, T cell polarisation and GVHD.
Significance: Once established, this model will be the first of its kind and will be an important tool to examine the influence of infection on inflammatory diseases.
Suitability: This project would suit a PhD student.
Supervisors: Dr Kate Gartlan (Kate.Gartlan@qimrberghofer.edu.au) and Prof Geoff Hill (Geoff.Hill@qimrberghofer.edu.au)
Background: Stem cell transplantation (SCT) is an effective cancer treatment, however its application is limited by graft-versus-host disease (GVHD), which has a major impact on patient morbidity and mortality. Unfortunately, GVHD severity and tumour clearance are positively correlated and therefore new therapies designed to reduce GVHD must be targeted, such that anti-tumour immunity is maintained. Donor T cell polarization is a critical factor influencing the severity and tissue distribution of graft-versus-host disease (GVHD) and the potency of graft-versus-leukaemia (GVL) effects after allo-SCT. We have identified a pathogenic donor T cell differentiation program that exacerbates GVHD without contributing to tumour clearance, which is characterised by a unique transcription factor expression profile.
Aims: This study will 1) examine T cell transcription factor expression after allo-SCT in both murine and clinical samples, and 2) utilise a small molecule inhibitor that modulates transcription factor expression to assess its therapeutic potential in the context of GVHD.
Significance: This therapeutic approach is highly novel and will provide the first essential proof-of-concept data to support small molecule modulation of T cell polarisation as a method for GVHD prevention and treatment.
Suitability: This project would suit either Honours or PhD students.
Supervisors: Dr Kate Gartlan (Kate.Gartlan@qimrberghofer.edu.au) and Prof Geoff Hill (Geoff.Hill@qimrberghofer.edu.au)
Characterising miRNA expression after bone marrow transplantation to develop novel therapeutics
Background: Micro RNAs (miRNAs) are small RNA molecules (~25 nucleotides) known to play an important role in regulating inflammation. Therefore miRNA may be a novel target to treat inflammatory diseases such as graft-versus-host disease (GVHD). GVHD develops in >50% of leukaemia patients that receive a donor stem cell/bone marrow transplant (SCT/BMT). GVHD has a major impact on the mortality and quality-of-life for these cancer survivors, however treatment options are very limited and steroid refractory GVHD patients (~20%) have particularly high mortality rates. Unfortunately, GVHD severity and tumour clearance are positively correlated, which means a balance must be struck between providing anti-tumour immunity and reducing the risks associated with GVHD. Our laboratory is therefore investigating novel therapeutics such as miRNAs to modulate inflammatory responses after BMT/SCT.
Aims: We are currently offering a project designed to 1) characterise miRNA expression profiles in patient serum after BMT/SCT and 2) to evaluate potential inflammatory biomarkers of GVHD.
Significance: New therapies are urgently needed to minimise the effects of GVHD after donor SCT/BMT. This project will use molecular and cell biology techniques and clinical samples to identify potential new targets for GVHD immunotherapy.
Suitability: This project would suit either Honours or PhD students.
Supervisors: Dr Kate Gartlan (Kate.Gartlan@qimrberghofer.edu.au) and Prof Geoff Hill (Geoff.Hill@qimrberghofer.edu.au)
Gartlan, Kate H., Koyama, Motoko, Lineburg, Katie E., Chang, Karshing, Ensbey, Kathleen S., Kuns, Rachel D., Henden, Andrea S., Samson, Luke D., Clouston, Andrew D., Lopez, Angel F., MacDonald, Kelli P. A. and Hill, Geoffrey R. (2019). Donor T-cell–derived GM-CSF drives alloantigen presentation by dendritic cells in the gastrointestinal tract. Blood Advances, 3 (19), 2859-2865. doi: 10.1182/bloodadvances.2019000053
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
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
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
Type-1 regulatory T cells are critical for curative immunotherapy outcomes
Zhang, ping, Gartlan, Kate H, Minnie, Simone A, Yeh, Albert, Takahashi, Shuichiro, Atilla, Erden, Nemychenkov, Nicole S, Boiko, Julie R, Schmidt, Christine R, Legg, Samuel RW, Sekiguchi, Tomoko, Ensbey, Kathleen S, Koyama, Motoko, Furlan, Scott N and Hill, Geoffrey R (2023). Type-1 regulatory T cells are critical for curative immunotherapy outcomes. The Journal of Immunology, 210 (1_Supplement), 173.11-173.11. doi: 10.4049/jimmunol.210.supp.173.11
Browne, Daniel J., Liang, Fang, Gartlan, Kate H., Harris, Patrick N. A., Hill, Geoffrey R., Corrie, Simon R. and Markey, Kate A. (2022). Multiplex microsphere PCR (mmPCR) allows simultaneous gram typing, detection of fungal DNA, and antibiotic resistance genes. Laboratory Medicine, 53 (5), 459-464. doi: 10.1093/labmed/lmac023
Gartlan, Kate H., Jaiswal, Jagdish K., Bull, Matthew R., Akhlaghi, Hedieh, Sutton, Vivien R., Alexander, Kylie A., Chang, Karshing, Hill, Geoffrey R., Miller, Christian K., O'Connor, Patrick D., Jose, Jiney, Trapani, Joseph A., Charman, Susan A., Spicer, Julie A. and Jamieson, Stephen M. F. (2022). Preclinical activity and pharmacokinetic/pharmacodynamic relationship for a series of novel benzenesulfonamide perforin inhibitors. ACS Pharmacology and Translational Science, 5 (6), 429-439. doi: 10.1021/acsptsci.2c00009
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
Mithraprabhu, Sridurga, Kalff, Anna, Gartlan, Kate H., Savvidou, Ioanna, Khong, Tiffany, Ramachandran, Malarmathy, Cooke, Rachel E., Bowen, Kathryn, Hill, Geoffrey R., Reynolds, John and Spencer, Andrew (2021). Phase II trial of single-agent panobinostat consolidation improves responses after sub-optimal transplant outcomes in multiple myeloma. British Journal of Haematology, 193 (1), 160-170. doi: 10.1111/bjh.17080
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
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
Gartlan, Kate H, Wilkinson, Andrew, Chang, Karshing, Kuns, Rachel D, Henden, Andrea, Minnie, Simone A, Ensbey, Kathleen S, Clouston, Andrew, Zhang, Ping, Koyama, Motoko, Hidalgo, Juan, Rose-John, Stefan, Varelias, Antiopi, Vuckovic, Slavica and Hill, Geoffrey R (2020). Diverse IL-6 signalling modalities drive pathogenic T cell differentiation and graft-versus-host-disease after allotransplantation. The Journal of Immunology, 204 (1_Supplement), 87.33-87.33. doi: 10.4049/jimmunol.204.supp.87.33
Minnie, Simone A, Kuns, Rachel D, Ensbey, Kathleen S, Samson, Luke D, Chesi, Marta, Gartlan, Kate H, Smyth, Mark J, Vuckovic, Slavica and Hill, Geoffrey R (2020). Posttransplant cyclophosphamide as a platform for immunotherapy after allogeneic stem cell transplantation for multiple myeloma. The Journal of Immunology, 204 (1_Supplement), 87.30-87.30. doi: 10.4049/jimmunol.204.supp.87.30
Minnie, S. A., Kuns, R. D. and Gartlan, K. H. (2019). Erratum: Myeloma escape after stem cell transplantation is a consequence of T-cell exhaustion and is prevented by TIGIT blockade(Blood (2018) 132:16 (1675-1688) DOI: 10.1182/blood-2018-01-825240). Blood, 134 (21), 1878-1878. doi: 10.1182/blood.2019003727
Gartlan, Kate H., Koyama, Motoko, Lineburg, Katie E., Chang, Karshing, Ensbey, Kathleen S., Kuns, Rachel D., Henden, Andrea S., Samson, Luke D., Clouston, Andrew D., Lopez, Angel F., MacDonald, Kelli P. A. and Hill, Geoffrey R. (2019). Donor T-cell–derived GM-CSF drives alloantigen presentation by dendritic cells in the gastrointestinal tract. Blood Advances, 3 (19), 2859-2865. doi: 10.1182/bloodadvances.2019000053
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
Spicer, Julie A., Miller, Christian K., O'Connor, Patrick D., Jose, Jiney, Giddens, Anna C., Jaiswal, Jagdish K., Jamieson, Stephen M. F., Bull, Matthew R., Denny, William A., Akhlaghi, Hedieh, Trapani, Joseph A., Hill, Geoff R., Chang, Karshing and Gartlan, Kate H. (2019). Inhibition of the cytolytic protein perforin prevents rejection of transplanted bone marrow stem cells in vivo. Journal of Medicinal Chemistry, 63 (5) acs.jmedchem.9b00881, 2229-2239. doi: 10.1021/acs.jmedchem.9b00881
Imaging flow cytometry to assess antigen-presenting-cell function
Markey, Kate A. and Gartlan, Kate H. (2019). Imaging flow cytometry to assess antigen-presenting-cell function. Current Protocols in Immunology, 125 (1) e72. doi: 10.1002/cpim.72
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
Perforin inhibition protects from lethal endothelial damage during fulminant viral hepatitis
Welz, M., Eickhoff, S., Abdullah, Z., Trebicka, J., Gartlan, K. H., Spicer, J. A., Demetris, A. J., Akhlaghi, H., Anton, M., Manske, K., Zehn, D., Nieswandt, B., Kurts, C., Trapani, J. A., Knolle, P., Wohlleber, D. and Kastenmüller, W. (2018). Perforin inhibition protects from lethal endothelial damage during fulminant viral hepatitis. Nature Communications, 9 (1) 4805, 4805. doi: 10.1038/s41467-018-07213-x
Minnie, Simone A., Kuns, Rachel D., Gartlan, Kate H., Zhang, Ping, Wilkinson, Andrew N., Samson, Luke, Guillerey, Camille, Engwerda, Christian, MacDonald, Kelli P. A., Smyth, Mark J., Markey, Kate A., Vuckovic, Slavica and Hill, Geoffrey R. (2018). Myeloma escape after stem cell transplantation is a consequence of t-cell exhaustion and is prevented by tigit blockade. Blood, 132 (16), 1675-1688. doi: 10.1182/blood-2018-01-825240
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
Wilkinson, Andrew N., Kuns, Rachel D., Varelias, Antiopi, Vuckovic, Slavica, Rose-John, Stefan, Gartlan, Kate H. and Hill, Geoffrey R. (2018). DISTINCT IL-6 SIGNALING PATHWAYS DRIVE ALTERNATE PATHOGENIC T CELL DIFFERENTIATION AND GVHD AFTER TRANSPLANT IN VIVO. The Journal of Immunology, 200 (1_Supplement), 55.2-55.2. doi: 10.4049/jimmunol.200.supp.55.2
Recipient mucosal-associated invariant T cells control graft-versus-host-disease within the colon
Varelias, Antiopi, Bunting, Mark, Ormerod, Kate, Koyama, Motoko, Olver, Stuart, Straube, Jasmin, Kuns, Rachel, Robb, Renee, Henden, Andrea, Cooper, Leanne, Lachner, Nancy, Gartlan, Kate, Lantz, Olivier J., Kjer-Nielsen, Lars, Mak, Jeffrey, Fairlie, David, Clouston, Andrew, McCluskey, James, Rossjohn, Jamie, Lane, Steven, Hugenholtz, Phil and Hill, Geoff (2018). Recipient mucosal-associated invariant T cells control graft-versus-host-disease within the colon. The Journal of Immunology, 200 (1_Supplement), 55.15-55.15. doi: 10.4049/jimmunol.200.supp.55.15
Minnie, Simone, Vuckovic, Slavica, Smith, David, Gartlan, Kate H., Watkins, Thomas S., Kuns, Rachel D., Guillerey, Camille, Chesi, Marta, Markey, Kate A., Miles, John J., Smyth, Mark J. and Hill, Geoffrey R. (2018). Syngeneic stem cell transplantation generates antigen-specific T cells that maintain myeloma-immune equilibrium. The Journal of Immunology, 200 (1_Supplement), 55.19-55.19. doi: 10.4049/jimmunol.200.supp.55.19
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
Granulocytes are unresponsive to IL-6 due to an absence of gp130
Wilkinson, Andrew N., Gartlan, Kate H., Kelly, Greg, Samson, Luke D., Olver, Stuart D., Avery, Judy, Zomerdijk, Nienke, Tey, Siok-Keen, Lee, Jason S., Vuckovic, Slavica and Hill, Geoffrey R. (2018). Granulocytes are unresponsive to IL-6 due to an absence of gp130. Journal of Immunology, 200 (9), 3547-3555. doi: 10.4049/jimmunol.1701191
Markey, Kate A., Gartlan, Kate H., Kuns, Rachel D., Lane, Steven W. and Hill, Geoffrey R. (2018). Conventional dendritic cells are required for the cross-presentation of leukemia-specific antigen in a model of AML relapse post-BMT. Bone Marrow Transplantation, 53 (6), 800-803. doi: 10.1038/s41409-018-0148-y
Markey, Kate A., Kuns, Rachel D., Browne, Daniel J., Gartlan, Kate H., Robb, Renee J., Martins, J. Paulo, Henden, Andrea S., Minnie, Simone A., Cheong, Melody, Koyama, Motoko, Smyth, Mark J., Steptoe, Raymond J., Belz, Gabrielle, Brocker, Thomas, Degli-Esposti, Mariapia A., Lane, Steven W. and Hill, Geoffrey R. (2018). Flt-3L expansion of recipient CD8α+ dendritic cells deletes alloreactive donor T cells and represents an alternative to post-transplant cyclophosphamide for the prevention of GVHD. Clinical Cancer Research, 24 (7), 1604-1616. doi: 10.1158/1078-0432.CCR-17-2148
Liang, Fang, Browne, Daniel J., Gray, Megan J., Gartlan, Kate H., Smith, David D., Barnard, Ross T., Hill, Geoffrey R., Corrie, Simon R. and Markey, Kate A. (2018). Development of a Multiplexed Microsphere PCR for Culture-Free Detection and Gram-Typing of Bacteria in Human Blood Samples. ACS Infectious Diseases, 4 (5), 837-844. doi: 10.1021/acsinfecdis.7b00277
Khoury, David S., Cromer, Deborah, Elliott, Trish, Soon, Megan S. F., Thomas, Bryce S., James, Kylie R., Best, Shannon E., Aogo, Rosemary A., Engel, Jessica A., Gartlan, Kate H., Akter, Jasmin, Sebina, Ismail, Haque, Ashraful and Davenport, Miles P. (2017). Characterising the effect of antimalarial drugs on the maturation and clearance of murine blood-stage Plasmodium parasites in vivo. International Journal for Parasitology, 47 (14), 913-922. doi: 10.1016/j.ijpara.2017.05.009
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
Forcade, Edouard, Paz, Katelyn, Flynn, Ryan, Griesenauer, Brad, Amet, Tohti, Li, Wei, Liu, Liangyi, Bakoyannis, Giorgos, Jiang, Di, Chu, Hong Wei, Lobera, Mercedes, Yang, Jianfei, Wilkes, David S., Du, Jing, Gartlan, Kate, Hill, Geoffrey R., MacDonald, Kelli P. A., Espada, Eduardo L., Blanco, Patrick, Serody, Jonathan S., Koreth, John, Cutler, Corey S., Antin, Joseph H., Soiffer, Robert J., Ritz, Jerome, Paczesny, Sophie and Blazar, Bruce R. (2017). An activated Th17-prone T cell subset involved in chronic graft-versus-host disease sensitive to pharmacological inhibition. JCI Insight, 2 (12) e92111. doi: 10.1172/jci.insight.92111
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 PA, Hugenholtz, Philip and Hill, Geoff R (2017). Acute graft-versus-host disease is regulated by an IL-17-sensitive microbiome. The Journal of Immunology, 198 (1_Supplement), 82.8-82.8. doi: 10.4049/jimmunol.198.supp.82.8
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
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
Gartlan, Kate H., Krashias, George, Wegmann, Frank, Hillson, William R., Scherer, Erin M., Greenberg, Philip D., Eisenbarth, Stephanie C., Moghaddam, Amin E. and Sattentau, Quentin J. (2016). Sterile inflammation induced by Carbopol elicits robust adaptive immune responses in the absence of pathogen-associated molecular patterns. Vaccine, 34 (19), 2188-2196. doi: 10.1016/j.vaccine.2016.03.025
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
Wegmann, Frank, Moghaddam, Amin E., Schiffner, Torben, Gartlan, Kate H., Powell, Timothy J., Russell, Rebecca A., Baart, Matthijs, Carrow, Emily W. and Sattentau, Quentin J. (2015). The carbomer-lecithin adjuvant Adjuplex has potent immunoactivating properties and elicits protective adaptive immunity against influenza virus challenge in mice. Clinical and Vaccine Immunology, 22 (9), 1004-1012. doi: 10.1128/CVI.00736-14
Imaging the immunological synapse between dendritic cells and T cells
Markey, Kate A., Gartlan, Kate H., Kuns, Rachel D., MacDonald, Kelli P. A. and Hill, Geoffrey R. (2015). Imaging the immunological synapse between dendritic cells and T cells. Journal of Immunological Methods, 423, 40-44. doi: 10.1016/j.jim.2015.04.029
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
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
Moghaddam, Amin E., Hillson, William R., Noti, Mario, Gartlan, Kate H., Johnson, Steven, Thomas, Benjamin, Artis, David and Sattentau, Quentin J. (2014). Dry roasting enhances peanut-induced allergic sensitization across mucosal and cutaneous routes in mice. Journal of Allergy and Clinical Immunology, 134 (6), 1453-1456. doi: 10.1016/j.jaci.2014.07.032
Polyethyleneimine is a potent systemic adjuvant for glycoprotein antigens
Sheppard, Neil C., Brinckmann, Sarah A., Gartlan, Kate H., Puthia, Manoj, Svanborg, Catharina, Krashias, George, Eisenbarth, Stephanie C., Flavell, Richard A., Sattentau, Quentin J. and Wegmann, Frank (2014). Polyethyleneimine is a potent systemic adjuvant for glycoprotein antigens. International Immunology, 26 (10), 531-538. doi: 10.1093/intimm/dxu055
Markey, Kate A., Koyama, Motoko, Gartlan, Kate H., Leveque, Lucie, Kuns, Rachel D., Lineburg, Katie E., Teal, Bianca E., MacDonald, Kelli P. A. and Hill, Geoffrey R. (2014). Cross-dressing by donor dendritic cells after allogeneic bone marrow transplantation contributes to formation of the immunological synapse and maximizes responses to indirectly presented antigen. Journal of Immunology, 192 (11), 5426-5433. doi: 10.4049/jimmunol.1302490
Gartlan, Kate H., Wee, Janet L., Demaria, Maria C., Nastovska, Roza, Chang, Tsz Man, Jones, Eleanor L., Apostolopoulos, Vasso, Pietersz, Geoffrey A., Hickey, Michael J., van Spriel, Annemiek B. and Wright, Mark D. (2013). Tetraspanin CD37 contributes to the initiation of cellular immunity by promoting dendritic cell migration. European Journal of Immunology, 43 (5), 1208-1219. doi: 10.1002/eji.201242730
van Spriel, Annemiek B., de Keijzer, Sandra, van der Schaaf, Alie, Gartlan, Kate H., Sofi, Mariam, Light, Amanda, Linssen, Peter C., Boezeman, Jan B., Zuidscherwoude, Malou, Reinieren-Beeren, Inge, Cambi, Alessandra, Mackay, Fabienne, Tarlinton, David M., Figdor, Carl G. and Wright, Mark D. (2012). The tetraspanin CD37 orchestrates the alpha(4)beta(1) integrin-Akt signaling axis and supports long-lived plasma cell survival. Science Signaling, 5 (250) ra82, ra82-ra82. doi: 10.1126/scisignal.2003113
Polyethyleneimine is a potent mucosal adjuvant for viral glycoprotein antigens
Wegmann, Frank, Gartlan, Kate H., Harandi, Ali M., Brinckmann, Sarah A., Coccia, Margherita, Hillson, William R., Kok, Wai Ling, Cole, Suzanne, Ho, Ling-Pei, Lambe, Teresa, Puthia, Manoj, Svanborg, Catharina, Scherer, Erin M., Krashias, George, Williams, Adam, Blattman, Joseph N., Greenberg, Philip D., Flavell, Richard A., Moghaddam, Amin E., Sheppard, Neil C. and Sattentau, Quentin J. (2012). Polyethyleneimine is a potent mucosal adjuvant for viral glycoprotein antigens. Nature Biotechnology, 30 (9), 883-888. doi: 10.1038/nbt.2344
Moghaddam, Amin E., Gartlan, Kate H., Kong, Leopold and Sattentau, Quentin J. (2011). Reactive Carbonyls Are a Major Th2-Inducing Damage-Associated Molecular Pattern Generated by Oxidative Stress. Journal of Immunology, 187 (4), 1626-1633. doi: 10.4049/jimmunol.1003906
A complementary role for the tetraspanins CD37 and Tssc6 in cellular immunity
Gartlan, Kate H., Belz, Gabrielle T., Tarrant, Jacqueline M., Minigo, Gabriela, Katsara, Maria, Sheng, Kuo-Ching, Sofi, Mariam, van Spriel, Annemiek B., Apostolopoulos, Vasso, Plebanski, Magdalena, Robb, Lorraine and Wright, Mark D. (2010). A complementary role for the tetraspanins CD37 and Tssc6 in cellular immunity. Journal of Immunology, 185 (6), 3158-3166. doi: 10.4049/jimmunol.0902867
The Tetraspanin Protein CD37 Regulates IgA Responses and Anti-Fungal Immunity
van Spriel, Annemiek B., Sofi, Mariam, Gartlan, Kate H., van der Schaaf, Alie, Verschueren, Ineke, Torensma, Ruurd, Raymakers, Reinier A. P., Loveland, Bruce E., Netea, Mihai G., Adema, Gosse J., Wright, Mark D. and Figdor, Carl G. (2009). The Tetraspanin Protein CD37 Regulates IgA Responses and Anti-Fungal Immunity. Plos Pathogens, 5 (3), e1000338. doi: 10.1371/journal.ppat.1000338
Tetraspanins CD37 and CD151 differentially regulate Ag presentation and T-cell co-stimulation by DC
Sheng, Kuo-Ching, van Spriel, Annemiek B., Gartlan, Kate H., Sofi, Mariam, Apostolopoulos, Vasso, Ashman, Leonie and Wright, Mark D. (2009). Tetraspanins CD37 and CD151 differentially regulate Ag presentation and T-cell co-stimulation by DC. European Journal of Immunology, 39 (1), 50-55. doi: 10.1002/eji.200838798
Signal regulatory protein molecules are differentially expressed by CD8(-) dendritic cells
Lahoud, Mireille H., Proietto, Anna I., Gartlan, Kate H., Kitsoulis, Susie, Curtis, Joan, Wettenhall, James, Sofi, Mariam, Daunt, Carmel, O'Keeffe, Meredith, Caminschi, Irina, Satterley, Keith, Rizzitelli, Alexandra, Schnorrer, Petra, Hinohara, Atsushi, Yamaguchi, Yasunori, Wu, Li, Smyth, Gordon, Handman, Emanuela, Shortman, Ken and Wright, Mark D. (2006). Signal regulatory protein molecules are differentially expressed by CD8(-) dendritic cells. Journal of Immunology, 177 (1), 372-382. doi: 10.4049/jimmunol.177.1.372
Modulating Donor T Cell Polarisation After Bone Marrow Transplantation to Prevent Graft-Versus-Host Disease
Doctor Philosophy — Principal Advisor
Other advisors:
Anti-leukaemia effect of Interferons
(2019) Doctor Philosophy — Associate Advisor
Other advisors:
Understanding the role of IL-6 signalling in Graft-Versus-Host Disease (GVHD)
(2019) Doctor Philosophy — Associate Advisor
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.
What is the influence of infection driven T cell polarisation on graft-versus-host disease?
Background: Stem cell/bone marrow transplantation (SCT/BMT) is an important curative therapy for haematological malignancies and disorders; however graft-versus-host disease (GVHD) and infection are two major complications of this procedure. Whilst it is well established that viral and bacterial infections influence GVHD pathogenesis, the impact of fungal infection after transplant is poorly understood. In non-transplant settings, adaptive immune responses to fungal infections are commonly associated with IL-17 production by T cells that enhance anti-fungal immunity. However our laboratory and others have demonstrated that the IL-17 differentiation pathway is pathogenic in the context of allotransplantation. We are offering a project designed to understand the relationship between fungal infection and GVHD outcomes.
Aims: This project aims to 1) establish an in vivo infection model that can be used in conjunction with bone marrow transplant in pre-clinical experimental systems. 2) Explore the relationship between fungal infection, T cell polarisation and GVHD.
Significance: Once established, this model will be the first of its kind and will be an important tool to examine the influence of infection on inflammatory diseases.
Suitability: This project would suit a PhD student.
Supervisors: Dr Kate Gartlan (Kate.Gartlan@qimrberghofer.edu.au) and Prof Geoff Hill (Geoff.Hill@qimrberghofer.edu.au)
Background: Stem cell transplantation (SCT) is an effective cancer treatment, however its application is limited by graft-versus-host disease (GVHD), which has a major impact on patient morbidity and mortality. Unfortunately, GVHD severity and tumour clearance are positively correlated and therefore new therapies designed to reduce GVHD must be targeted, such that anti-tumour immunity is maintained. Donor T cell polarization is a critical factor influencing the severity and tissue distribution of graft-versus-host disease (GVHD) and the potency of graft-versus-leukaemia (GVL) effects after allo-SCT. We have identified a pathogenic donor T cell differentiation program that exacerbates GVHD without contributing to tumour clearance, which is characterised by a unique transcription factor expression profile.
Aims: This study will 1) examine T cell transcription factor expression after allo-SCT in both murine and clinical samples, and 2) utilise a small molecule inhibitor that modulates transcription factor expression to assess its therapeutic potential in the context of GVHD.
Significance: This therapeutic approach is highly novel and will provide the first essential proof-of-concept data to support small molecule modulation of T cell polarisation as a method for GVHD prevention and treatment.
Suitability: This project would suit either Honours or PhD students.
Supervisors: Dr Kate Gartlan (Kate.Gartlan@qimrberghofer.edu.au) and Prof Geoff Hill (Geoff.Hill@qimrberghofer.edu.au)
Characterising miRNA expression after bone marrow transplantation to develop novel therapeutics
Background: Micro RNAs (miRNAs) are small RNA molecules (~25 nucleotides) known to play an important role in regulating inflammation. Therefore miRNA may be a novel target to treat inflammatory diseases such as graft-versus-host disease (GVHD). GVHD develops in >50% of leukaemia patients that receive a donor stem cell/bone marrow transplant (SCT/BMT). GVHD has a major impact on the mortality and quality-of-life for these cancer survivors, however treatment options are very limited and steroid refractory GVHD patients (~20%) have particularly high mortality rates. Unfortunately, GVHD severity and tumour clearance are positively correlated, which means a balance must be struck between providing anti-tumour immunity and reducing the risks associated with GVHD. Our laboratory is therefore investigating novel therapeutics such as miRNAs to modulate inflammatory responses after BMT/SCT.
Aims: We are currently offering a project designed to 1) characterise miRNA expression profiles in patient serum after BMT/SCT and 2) to evaluate potential inflammatory biomarkers of GVHD.
Significance: New therapies are urgently needed to minimise the effects of GVHD after donor SCT/BMT. This project will use molecular and cell biology techniques and clinical samples to identify potential new targets for GVHD immunotherapy.
Suitability: This project would suit either Honours or PhD students.
Supervisors: Dr Kate Gartlan (Kate.Gartlan@qimrberghofer.edu.au) and Prof Geoff Hill (Geoff.Hill@qimrberghofer.edu.au)