Adelaide Medical School
Faculty of Health and Medical Sciences
Dr Lisa Ebert is an Affiliate Senior Lecturer of the University of Adelaide (Adelaide Medical School) and a Senior Research Fellow in the Translational Oncology Laboratory at the Centre for Cancer Biology. The Translational Oncology Laboratory has a clear focus on the development of new and better therapies for cancer, and the translation of these research discoveries to the clinic. The head of the group, Professor Michael Brown, is a medical oncologist and Director of the Cancer Clinical Trials Unit at the Royal Adelaide Hospital. Thus, we are perfectly positioned to study human cancer and to adopt a ‘bench to bedside’ approach for the testing of new therapeutic strategies in the clinic.
The Translational Oncology group has two major research streams: one focussed on T cell-based cancer immunotherapies, and the other on antibody-targeted diagnostics and therapeutics.
Dr Ebert directs a research program within the T Cell Immunotherapies stream. Our team has a major interest in chimeric antigen receptor (CAR)-T cell therapies, where our studies range from the identification of new target antigens, to the design, manufacturing and testing of novel CAR-T cell therapies, and all the way to clinical trials. Our other major interest is in Immune Checkpoint Inhibitor therapies. We use patient blood and tissue specimens to better understand the mechanism of action of these novel agents, with the hope of improving the number of patients that can benefit, and to predict upfront the those patients who will respond best to treatment.
Student projects are available in our group for Honours, Masters and PhD. Some examples are listed below:
Improving the tissue-homing capacity of CAR-T cells
Chimeric antigen receptor (CAR)-T cell therapy has revolutionised the treatment of B cell leukaemia and lymphoma, and has spurred intense interest in extending these successes to the treatment of solid tumours such as glioblastoma, melanoma and sarcoma. In clinical trials at the Royal Adelaide Hospital, and in pre-clinical studies using advanced mouse models, we are testing CAR-T cells for their ability to shrink these tumours. We are also particularly interested to understand how effectively these T cells can pass from the blood circulation into tumour tissues, which is where they are required to mediate their cancer cell-killing function. Projects are available to address these questions using in vitro functional assays, animal models and analysis of patient blood and tissue samples. These studies are expected to improve our understanding of anti-tumour immunity and ultimately to enhance the efficacy of our clinical CAR-T cell therapies.
Understanding and predicting individual patient responses to Immune Checkpoint Inhibitor (ICI) therapy
ICI therapy is a radical therapeutic approach that is now approved in Australia for the treatment of several cancer types, including melanoma, lung and kidney. These new medicines can re-activate dormant anti-tumour immune responses, leading to dramatic tumour shrinkage, and possibly cure, in a fraction of patients. However, most patients receive little to no benefit, yet are still exposed to the risk of severe side effects. Using pre-treatment blood samples from melanoma patients, we have discovered a way to predict which of these patients will experience significant tumour shrinkage following ICI therapy. Projects are available to further develop this finding, including: (i) using this knowledge to better understand the mechanism of action for ICI therapy; (ii) testing whether this approach also works for patients with other types of cancer; and (iii) translating this discovery into a clinically useful blood test that could be used to ensure that each patient receives the most effective treatment for them.
Location: Centre for Cancer Biology (UniSA Cancer Research Institute/Bradley Building – adjacent to AHMS building on North Tce)
Research project start: Semester 1 or Semester 2
Special requirements: Some vaccinations may be required if handling human specimens
Year Citation 2020 Ebert, L. M., Yu, W., Gargett, T., Toubia, J., Kollis, P. M., Tea, M. N., . . . Brown, M. P. (2020). Endothelial, pericyte and tumor cell expression in glioblastoma identifies fibroblast activation protein (FAP) as an excellent target for immunotherapy. Clinical and Translational Immunology, 9(10), e1191.
2020 Martini, C., Thompson, E. J., Hyslop, S. R., Cockshell, M. P., Dale, B. J., Ebert, L. M., . . . Bonder, C. S. (2020). Platelets disrupt vasculogenic mimicry by cancer cells. Scientific Reports, 10(1), 5869-1-5869-18.
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2020 Zadeh Shirazi, A., Fornaciari, E., Bagherian, N. S., Ebert, L. M., Koszyca, B., & Gomez, G. A. (2020). DeepSurvNet: deep survival convolutional network for brain cancer survival rate classification based on histopathological images. Medical and Biological Engineering and Computing, 58(5), 1031-1045.
2019 Perrin, S. L., Samuel, M. S., Koszyca, B., Brown, M. P., Ebert, L. M., Oksdath, M., & Gomez, G. A. (2019). Glioblastoma heterogeneity and the tumour microenvironment: implications for preclinical research and development of new treatments. Biochemical Society Transactions, 47(2), 625-638.
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2019 Gargett, T., TRUONG, N., EBERT, L., YU, W., & BROWN, M. (2019). Optimization of manufacturing conditions for chimeric antigen receptor T cells to favor cells with a central memory phenotype. Cytotherapy, 21(6), 593-602.
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2019 Brown, M. P., Ebert, L. M., & Gargett, T. (2019). Clinical chimeric antigen receptor-T cell therapy: a new and promising treatment modality for glioblastoma. Clinical and Translational Immunology, 8(5), 20 pages.
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2019 Gomez, G. A., Oksdath, M., Brown, M. P., & Ebert, L. M. (2019). New approaches to model glioblastoma in vitro using brain organoids: implications for precision oncology. Translational Cancer Research, 8(Suppl. 6), S606-S611.
2018 Ebert, L., Yu, W., Gargett, T., & Brown, M. (2018). Logic-gated approaches to extend the utility of chimeric antigen receptor T-cell technology. Biochemical Society Transactions, 46(2), 391-401.
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2017 Davis, I. D., Quirk, J., Morris, L., Seddon, L., Tai, T. Y., Whitty, G., . . . Cebon, J. (2017). A pilot study of peripheral blood BDCA-1 (CD1c) positive dendritic cells pulsed with NY-ESO-1 ISCOMATRIX™ adjuvant. Immunotherapy, 9(3), 249-259.
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2017 Tan, L. Y., Martini, C., Fridlender, Z. G., Bonder, C. S., Brown, M. P., & Ebert, L. M. (2017). Control of immune cell entry through the tumour vasculature: a missing link in optimising melanoma immunotherapy?. Clinical and Translational Immunology, 6(3), e134-1-e134-9.
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2016 Ebert, L., Tan, L., Johan, M., Min, K., Cockshell, M., Parham, K., . . . Bonder, C. (2016). A non-canonical role for desmoglein-2 in endothelial cells: implications for neoangiogenesis. Angiogenesis, 19(4), 463-486.
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2016 Tan, L., Mintoff, C., Johan, M., Ebert, B., Fedele, C., Zhang, Y., . . . Ebert, L. (2016). Desmoglein 2 promotes vasculogenic mimicry in melanoma and is associated with poor clinical outcome. Oncotarget, 7(29), 46492-46508.
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2015 Pitman, M., Powell, J., Coolen, C., Moretti, P., Zebol, J., Pham, D., . . . Pitson, S. (2015). A selective ATP-competitive sphingosine kinase inhibitor demonstrates anti-cancer properties. Oncotarget, 6(9), 7065-7083.
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2015 Moldenhauer, L., Cockshell, M., Frost, L., Parham, K., Tvorogov, D., Tan, L., . . . Bonder, C. (2015). Interleukin-3 greatly expands non-adherent endothelial forming cells with pro-angiogenic properties. Stem Cell Research, 14(3), 380-395.
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2014 Tan, B., Anaka, M., Deb, S., Freyer, C., Ebert, L., Chueh, A., . . . Mariadason, J. (2014). FOXP3 over-expression inhibits melanoma tumorigenesis via effects on proliferation and apoptosis. Oncotarget, 5(1), 264-276.
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2013 Bonder, C., & Ebert, L. (2013). Fos-icking for control of angiogenesis: Increasing the longevity of peritoneal dialysis. Kidney International, 84(6), 1065-1067.
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2013 Klein, O., Ebert, L., Zanker, D., Woods, K., Tan, B., Fucikova, J., . . . Cebon, J. (2013). Flt3 ligand expands CD4⁺FoxP3⁺ regulatory T cells in human subjects. European Journal of Immunology, 43(2), 533-539.
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2012 Ebert, L., MacRaild, S., Zanker, D., Davis, I., Cebon, J., & Chen, W. (2012). A cancer vaccine induces expansion of NY-ESO-1-specific regulatory T cells in patients with advanced melanoma. PLoS ONE, 7(10), e48424-1-e48424-10.
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2012 Ebert, L., MacRaild, S., Davis, I., Cebon, J., & Chen, W. (2012). A novel method for detecting antigen-specific human regulatory T cells. Journal of Immunological Methods, 377(1-2), 56-61.
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2010 Cebon, J., Knights, A., Ebert, L., Jackson, H., & Chen, W. (2010). Evaluation of cellular immune responses in cancer vaccine recipients: Lessons from NY-ESO-1. Expert Review of Vaccines, 9(6), 617-629.
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2009 Klein, O., Ebert, L., Nicholaou, T., Browning, J., Russell, S., Zuber, M., . . . Cebon, J. (2009). Melan-a-specific cytotoxic T cells are associated with tumor regression and autoimmunity following treatment with anti-CTLA-4. Clinical Cancer Research, 15(7), 2507-2513.
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2009 Nicholaou, T., Ebert, L. M., Davis, I. D., McArthur, G. A., Jackson, H., Dimopoulos, N., . . . Cebon, J. (2009). Regulatory T-Cell-mediated attenuation of T-Cell responses to the NY-ESO-1ISCOMATRIX vaccine in patients with advanced malignant melanoma. Clinical Cancer Research, 15(6), 2166-2173.
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2009 Ebert, L. M., Yu, C. L., Clements, C. S., Robson, N. C., Jackson, H. M., Markby, J. L., . . . Chen, W. (2009). A long, naturally presented immunodominant epitope from NY-ESO-1 tumor antigen: Implications for cancer vaccine design. Cancer Research, 69(3), 1046-1054.
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2009 Dimopoulos, N., Jackson, H. M., Ebert, L., Guillaume, P., Luescher, I. F., Ritter, G., & Chen, W. (2009). Combining MHC tetramer and intracellular cytokine staining for CD8<sup>+</sup> T cells to reveal antigenic epitopes naturally presented on tumor cells. Journal of Immunological Methods, 340(1), 90-94.
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2009 Ebert, L. M., Liu, Y. C., Clements, C. S., Robson, N. C., Jackson, H. M., Markby, J. L., . . . Chen, W. (2009). A long, naturally presented immunodominant epitope from NY-ESO-1 tumor antigen: Implications for cancer vaccine design (Cancer Research (2009) 69, (1046-54)). Cancer Research, 69(10), 4553.
2008 Ebert, L. M., Bee, S. T., Browning, J., Svobodova, S., Russell, S. E., Kirkpatrick, N., . . . Chen, W. (2008). The regulatory T cell-associated transcription factor FoxP3 is expressed by tumor cells. Cancer Research, 68(8), 3001-3009.
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2006 Schaerli, P., Ebert, L. M., & Moser, B. (2006). Comment on "The vast majority of CLA<sup>+</sup> T cells are resident in normal skin" . Journal of Immunology, 177(3), 1375-1376.
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2006 Ebert, L., Meuter, S., & Moser, B. (2006). Homing and function of human skin γδ T cells and NK cells: Relevance for tumor surveillance. Journal of Immunology, 176(7), 4331-4336.
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2006 Nicholaou, T., Ebert, L., Davis, I. D., Robson, N., Klein, O., Maraskovsky, E., . . . Cebon, J. (2006). Directions in the immune targeting of cancer: Lessons learned from the cancer-testis Ag NY-ESO-1. Immunology and Cell Biology, 84(3), 303-317.
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2005 Schaerli, P., Willimann, K., Ebert, L., Walz, A., & Moser, B. (2005). Cutaneous CXCL14 targets blood precursors to epidermal niches for langerhans cell differentiation. Immunity, 23(3), 331-342.
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2004 Ebert, L., Horn, M., Lang, A., & Moser, B. (2004). B cells alter the phenotype and function of follicular-homing CXCR5<sup>+</sup> T cells. European Journal of Immunology, 34(12), 3562-3571.
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2004 Schaerli, P., Ebert, L., Willimann, K., Blaser, A., Roos, R., Loetscher, P., & Moser, B. (2004). A Skin-selective Homing Mechanism for Human Immune Surveillance T Cells. Journal of Experimental Medicine, 199(9), 1265-1275.
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2002 Ebert, L., & McColl, S. (2002). Up-regulation of CCR5 and CCR6 on distinct subpopulations of antigen-activated CD4⁺ T lymphocytes. Journal of Immunology, 168(1), 65-72.
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2001 Ebert, L., & McColl, S. (2001). Coregulation of CXC chemokine receptor and CD4 expression on T lymphocytes during allogeneic activation. Journal of Immunology, 166(8), 4870-4878.
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1999 Gale, L., & McColl, S. (1999). Chemokines: extracellular messengers for all occasions?. Bioessays, 21(1), 17-28.
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Year Citation 2005 Ebert, L., Schaerli, P., & Moser, B. (2005). Chemokine-mediated control of T cell traffic in lymphoid and peripheral tissues. In Molecular Immunology Vol. 42 (pp. 799-809). Quebec City, CANADA: PERGAMON-ELSEVIER SCIENCE LTD.
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2003 Moser, B., & Ebert, L. (2003). Lymphocyte traffic control by chemokines: Follicular B helper T cells. In Immunology Letters Vol. 85 (pp. 105-112). ELSIMORE, DENMARK: ELSEVIER.
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Current funding sources include Cancer Australia, the Neurosurgical Research Foundation, Tour de Cure and the Royal Adelaide Hospital Research Fund.
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