ACRF Translational Research Laboratory

Research Overview

The ACRF Translational Research Laboratory was established in 2013 and is located at The Royal Melbourne Hospital. Led by Professor David Ritchie, Head of Bone Marrow Transplantation and Deputy Head of Clinical Haematology, the laboratory is focused on translational and biomarker research in blood cancers and bone marrow failure disorders treated using novel therapies and/or bone marrow transplantation.

Our translational laboratory has a mission of undertaking projects utilising clinically derived samples from well-defined clinical cohorts of patients, applying high quality investigational assays and investigating the factors that determine clinical outcomes, treatment efficacy and exploring ways of improving the treatment of disease.

Central to our research is the availability of high quality primary samples from patients. The laboratory has been instrumental in the design and activation of clinical trials incorporating biobanking and biomarker analyses and currently supports the activities of more than 20 prospective clinical trials. These samples are analysed using cutting edge immunological and molecular techniques to identify biomarkers of cancer response to treatment.

We have current research projects in bone marrow transplantation, Acute Myeloid Leukaemia, Multiple Myeloma, Chronic Lymphocytic Leukaemia, Lymphoma and Myelodysplasia. The laboratory utilises a range of assays including a full suite of molecular techniques, cell culture techniques and extensive flow cytometry as well as where appropriate animal models and functional drug assays.

Our laboratory has a proud tradition of supporting students in their studies with more than 12 higher degree students supervised through our laboratory (Honours, Masters, PhD) in both laboratory and clinical based projects resulting in multiple conference presentations and publications. These studies have been translated to the clinic resulting in multiple investigator initiated clinical trials (including MicroLEN, Nivallo, RESELECT, VICTORY) which provide further opportunities for correlative analyses and clinical studies.

Students with a strong background immunology and/or laboratory techniques looking to expand their technical and research skills are especially encouraged to look at our current project listing and contact us if interested in undertaking a project through our laboratory.

Staff

  • A/Prof Rachel Koldej, Senior Scientist
  • Dr Joanne Davis, Postdoctoral Research Officer
  • Dr Lynette Chee, VCA Fellow and Clinical Haematologist
  • Dr Eric Wong, Clinical Haematologist
  • Dr Ashvind Prabahran, PhD student and BMT Fellow
  • Dr Ray Mun Koo, PhD student and BMT Fellow
  • Mrs Mandy Ludford-Menting, Research Assistant
  • Mr Nicholas Holzwart, Research Assistant
  • Mr Christopher Cotsopoulos, Research Technician
  • Ms Heather Lambie, Research Technician
  • Ms Mayani Rawicki, Research Facilitator

Funding

  • Medical Research Future Fund
  • Leukemia and Lymphoma Society
  • Fight Cancer Foundation
  • Royal Melbourne Hospital Foundation
  • Maddie Riewoldt’s Vision
  • Victorian Cancer Agency
  • NHMRC
  • Leukaemia Foundation Australia

Research Publications

  1. Prabahran A, Koldej R, Chee L, Szer J, and Ritchie D. Non-relapse cytopenias following allogeneic stem cell transplantation, a case review. Bone Marrow Transplantation. 2022, Jul 23.
  2. Chee L, Ritchie DS, Ludford-Menting M, Ripley J, Chung J, Park D, Norton S, Kenealy M and Koldej R. Dysregulation of immune cell and cytokine signalling correlates with clinical outcomes in myelodysplastic syndrome. European Journal of Haematology. 2022, Apr;108(4):342-353.
  3. Mehta PH, Fiorenza S, Koldej RM, Jaworowski A, Ritchie DS and Quinn KM. T cell fitness and autologous CAR-T cell therapy success in haematologic malignancy. Frontiers in Immunology. 25th November 2021.
  4. Davis JE, Du K, Ludford-Menting M, Prabahran A, Wong E, Huntington N, Koldej RM* and Ritchie DS*. Venetoclax or ruxolitinib in pre-transplant conditioning lower the engraftment barrier following allogeneic stem cell transplant in mice. Frontiers in Immunology, 24th Sept 2021.
  5. Davis JE, Sharpe C, Mason K, Tam, CS, Koldej RM* and Ritchie DS*. Ibrutinib protects T cells in patients with CLL from proliferation-induced senescence. Journal of Translational Medicine. 2021, 19:473.
  6. Koldej RM, Prabahran A, Tan CW, Ng AP, Davis MJ and Ritchie DS. Dissection of the bone marrow microenvironment in Hairy Cell Leukaemia identifies prognostic tumour and immune related biomarkers. Scientific Reports. 2021, 11:19056.
  7. Prabahran A, Koldej R, Chee L, and Ritchie D. Clinical features, pathophysiology and therapy of Poor Graft Function Post Allogeneic Stem Cell Transplantation. Blood Advances. 2022, Mar 22;6(6):1947-1959.
  8. Kuzich J, Kankanige Y, Guinto J, Ryland G, McBean M, Wong E, Koldej R, Collins J, Westerman D, Ritchie D and Blombery P. T cell receptor beta locus sequencing early post-allogeneic stem cell transplant identifies patients at risk of initial and recurrent cytomegalovirus infection. Bone Marrow Transplantation.
  9. Prabahran A, Koldej R, Chee L, Wong E and Ritchie D. Evaluation of risk factors for and subsequent mortality from poor graft function (PGF) post allogeneic stem cell transplantation. Leuk Lymphoma, 2021, Jan 31:1-13
  10. Davis JE, Handunnetti SM, Ludford-Menting M, Sharpe C, Blombery P, Anderson MA, Roberts AW, Seymour JF, Tam CS, Ritchie DS, Koldej RM. Immune recovery in patients with mantle cell lymphoma receiving long-term ibrutinib and venetoclax combination therapy. Blood Advances, 2020, Oct 13;4(19):4849-4859
  11. Cooke RE, Quinn KM, Harrison S, Quach H, Prince M, Koldej R and Ritchie D. Conventional Treatment for Multiple Myeloma Drives Premature Ageing Phenotypes and Metabolic Dysfunction in T cells. Frontiers in Immunology. 3 Sep. 2020
  12. Koldej R, and Ritchie D. High multiplex analysis of the immune microenvironment in bone marrow trephine samples using GeoMX digital spatial profiling. Immuno-Oncology Technology, 2020, 5:1-4
  13. Koldej R, Perera T, Collins J and Ritchie D. Association between P2X7 polymorphisms and post-transplant outcomes in allogeneic haematopoietic stem cell transplantation. Int. J. Mol. Sci. 2020, 21(11), 3772
  14. Quinn K, Kartikasari A, Cooke R, Koldej R, Ritchie D and Plebanski M. Impact of Age-, Cancer- and Treatment-Driven Inflammation on T Cell Function and Immunotherapy. Journal of Leukocyte Biology, 2020, Sept:108(3)
  15. Wong E, Davis JE, Koldej R, Szer J, Grigg A and Ritchie D. Nivolumab induces dynamic alterations in CD8 T-cell function and TIM-3 expression when used to treat relapsed acute myeloid leukaemia after allogeneic stem cell transplant. Leukemia and Lymphoma, 2020, Jan;61(1):185-188
  16. Cooke RE, Koldej R, Ritchie D. Immunotherapeutics in Multiple Myeloma: How Can Translational Mouse Models Help? J Oncol. 2019 Apr 10;2019:2186494
  17. Jiao Y, Davis JE, Rautela J, Carrington EM, Ludford-Menting MJ, Goh W, Delconte RB, Souza-Fonseca-Guimaraes F, Koldej R, Gray D, Huang D, Kile BT, Lew AM, Ritchie DS, Huntington ND. Recipient BCL2 inhibition and NK cell ablation form part of a reduced intensity conditioning regime that improves allo-bone marrow transplantation outcomes. Cell Death Differ. 2019 Aug;26(8):1516-1530
  18. Koldej R, Collins J, Ritchie D. P2X7 polymorphisms and stem cell mobilisation. Leukemia. 2018 Dec;32(12):2724-2726
  19. Mastaglio S, Wong E, Perera T, Ripley J, Blombery P, Smyth MJ, Koldej R, Ritchie D. Natural killer receptor ligand expression on acute myeloid leukemia impacts survival and relapse after chemotherapy. Blood Adv. 2018 Feb 27;2(4):335-346