The Antigen Presentation and Immunoregulation Laboratory investigates the contribution of donor and host antigen presenting cells (APCs) to immune responses following bone marrow stem cell transplantation. Basic research in immunology using preclinical models follows three streams: APC development, antigen presentation, and APC induced T cell responses and their regulation.
Group Leader: Dr Kelli MacDonald
- Dr Laetitia Le Texier, Research Officer
- Dr Michelle Melino, Research Officer
- Katie Lineburg, PhD Student
- Jemma Nicholls, PhD Student
- Christina Nalkurthi, PhD Student
- Bianca Teal, Research Assistant
- Justin Rich, Research Assistant
Globally, haematological malignancies represent the fifth most commonly occurring cancers and the second leading cause of cancer death. Hematopoietic stem cell transplantation (SCT) is the most effective curative therapy, and the therapy of choice for the majority of these cancers of bone marrow origin. The curative property of SCT lies in the graft-versus-leukemia effect which is required for ablation of residual cancer burden.
This process is absolutely dependent on donor T cells contained within the graft, however these T cells are also the primary mediators of graft versus host disease (GVHD), a life-threatening complication which significantly limits the success of SCT therapy. GVHD occurs in both acute (aGVHD) and chronic forms (cGVHD), which together contribute to the significant mortality and morbidity associated with SCT. Research undertaken in the Antigen Presentation and Immunoregulation Lab is primarily focused on using preclinical murine models to dissect the immune mechanisms underpinning GVHD.
Driven by the increasing prevalence and severity of cGVHD in clinical SCT patients, and the paucity of useful therapies for this disease, our research in the past 5 years has centred on determining the mechanistic mediators of the fibrotic manifestations of cGVHD. The overarching goal is to identify and translate novel effective therapies, as such our studies aim to identify targetable cellular and molecular mediators of cGVHD pathology, to confirm efficacy of targeted inhibition/promotion of these pathways in preclinical models of cGVHD and test these pathways in preclinical models of liver fibrosis to establish their broader application. Finally, targeted inhibition/promotion of these pathways will be tested in clinical SCT patients using established national and international clinical collaborations.
We have the following exciting projects that utilise novel reagents, animal models and a unique clinical sample bank, that are suitable for HDC students and have tailored projects for students entering the MD-PhD program. These projects will give students an understanding of cellular and molecular immunology with a focus on clinical translation.
- The effects of Ibrutinib on monocyte/macrophage differentiation after SCT
- The role of IL-17 signalling in monocytes and macrophages in promoting cGVHD
- Metabolic profiling of T cells in cGVHD
- The role of autophagy dependent regulatory T cells in the control of chronic graft versus host disease
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