Blood cancers, which include leukaemia, lymphoma and myeloma account for 10% of all cancers and 9.4% of cancer deaths (read more at this link). Stem cell or bone marrow transplantation is the predominant curative therapy for these diseases. However, the major complication is graft-versus-host disease (GVHD) in which the gastrointestinal tract, skin, lung and liver are preferentially damaged by the transplanted donor immune system, limiting the therapeutic potential of this treatment. Importantly, given the severe immunosuppression in these patients, infections are common and often fatal. Thus, there is a pressing need for new treatment approaches to improve transplant outcome for these patients.
The Transplantation Immunology Laboratory aims to improve our fundamental understanding of the pathophysiology of GVHD using innovative technologies and pre-clinical models of disease, with the view of translating these findings into clinical practice. The group’s research focuses on defining the immunological basis that underpins GVHD, with an emphasis on cellular and cytokine modulation of mucosal immunity during stem cell transplantation. This research will provide valuable insights that may inform of better therapeutic strategies for patients with GVHD.
Team Head: Associate Professor Antiopi Varelias
- Rachel Kuns, Research Assistant
- Stuart Olver, Research Assistant
- Maximillian Lacour, PhD Student
- Yashaswini Janardhanan, Masters Student
- Alika Collinge, Honours Student
- Bowerman KL, Varelias A, Lachner N, Kuns RD, Hill GR, Hugenholtz P. Continuous pre- and post- transplant exposure to a disease-associated gut microbiome promotes hyper-acute graft-versus-host disease in wildtype mice. Gut Microbes. 1-17 (2020).
- Koyama M, Mukhopadhyay P, Schuster IS, Henden AS, Hulsdunker J, Varelias A, Vetizou M, Kuns RD, Robb RJ, Zhang P, Blazar BR, Thomas R, Begun J, Waddell N, Trinchieri G, Zeiser R, Clouston AD, Degli-Esposti MA, Hill GR. 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 (2019).
- Yan J, Allen S, McDonald E, Das I, Mak J, Liu L, Fairlie D, Meehan B, Chen Z, Corbett A, Varelias A, Smyth M, Teng M. MAIT cells promote tumor initiation, growth and metastases via tumor MR1. Cancer Discov. 10(1):124-141 (2019).
- Varelias A, Gartlan KH, Wilkinson AN, Olver SD, Samson LD, Tey SK, MacDonald KPA, Hill GR. Expansion of IL-17A-secreting CD8+ mucosa-associated invariant T cells in peripheral blood following stem cell mobilization. Blood Adv. 12;3(5):718-723 (2019).
- Martins JP, Andoniou CE, Fleming P, Kuns RD, Schuster IS, Voigt V, Daly S, Varelias A, Tey SK, Degli-Esposti MA, Hill GR. Strain-specific antibody therapy prevents cytomegalovirus reactivation after transplantation. Science. 363(6424):288-293 (2019).
- Varelias A*, Bunting MD*, Ormerod KL, Koyama M, Olver SD, Straube J, Kuns RD, Robb RJ, Henden AS, Cooper L, Lachner N, Gartlan KH, Lantz O, Kjer-Nielsen L, Mak JYW, Fairlie DP, Clouston AD, McCluskey J, Rossjohn J, Lane SW, Hugenholtz P and Hill GR. Recipient Mucosal-Associated Invariant T Cells control GVHD within the colon. J Clin Invest. 128(5):1919-1936 (2018). *Joint first authors.
- Varelias A, Ormerod KL, Bunting MD, Koyama M, Gartlan KH, Kuns RD, Lachner N, Locke KR, Lim CY, Henden AS, Zhang P, Clouston AD, Hasnain SZ, McGuckin MA, Blazar BR, MacDonald KPA, Hugenholtz P and Hill GR. Acute graft-versus-host disease is regulated by an IL-17-sensitive microbiome. Blood. 129(15):2172-2185 (2017).
- Varelias A, Gartlan KH, Kreijveld E, Olver SD, Lor M, Kuns RD, Lineburg KE, Teal BE, Raffelt N,
Cheong M, Alexander KA, Koyama M, Markey KA, Sturgeon E, Leach J, Reddy P, Kennedy GA,
Yanik G, Blazar BR, Tey S-K, Clouston AD, MacDonald KPA, Cooke KR and Hill GR. Lung parenchyma–derived IL-6 promotes IL-17A–dependent acute lung injury after allogeneic stem cell transplantation. Blood. 125(15):2435-44 (2015).
- Kennedy GA*, Varelias A*, Vuckovic S, Le Texier L, Gartlan KH, Zhang P, Thomas G, Anderson L, Boyle G, Cloonan N, Leach J, Sturgeon E, Avery J, Olver SD, Lor M, Misra AK, Hutchins C, Morton AJ, Durrant STS, Subramoniapillai E, Butler JP, Curley CI, MacDonald KPA, Tey SK and Hill GR. Addition of IL-6 inhibition to standard GVHD prophylaxis after allogeneic stem cell transplantation: a phase I/II trial. Lancet Oncol. 15(13):1451-9 (2014). *Joint first authors.
- Koyama M, Kuns RD, Olver SD, Raffelt NC, Wilson YA, Don AL, Lineburg KE, Cheong M, Robb RJ, Markey KA, Varelias A, Malissen B, Hämmerling GJ, Clouston AD, Engwerda CR, Bhat P, MacDonald KP and Hill GR. Recipient nonhematopoietic antigen-presenting cells are sufficient to induce lethal acute graft-versus-host disease. Nat Med. 18(1):135-42 (2012).
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