![Professor Michelle Haber](https://api.research.unsw.edu.au/sites/default/files/images/profile/Michelle_April%202021v2.jpg)
Professor Michelle Haber
1984 PhD University of New South Wales
1978-79 PhD qualifying program University of New South Wales
1978 BSc (Psych) Honours Class 1, University Medal University of New South Wales
2008 D.Sc. honaris causa University of New South Wales
I am an international leader in childhood cancer research, and have made fundamental discoveries in the areas of drug resistance and novel therapeutics in neuroblastoma, as well as pioneering molecular diagnostics and precision medicine for Australian children with leukaemia and other high-risk cancers
As Executive Director of Children’s Cancer Institute, Co-Head of the Institute’s Molecular Targets and Cancer Therapeutics Theme and Head of the Experimental Therapeutics Group, I have conducted translational research developing novel diagnostics and therapeutics for aggressive child cancers which have changed clinical practice for Australian children with cancer, improving their survival and quality of life.
My research program is nationally and internationally recognised for research into the treatment of high-risk childhood cancers, focused on developing novel approaches through identifying molecular targets that drive cancer growth and development, developing new drugs to inhibit the action of these targets, and combining existing and new drug treatments into novel therapeutic approaches that can be rapidly translated into national and international clinical trials.
- Publications
- Grants
- Awards
- Research Activities
- Engagement
- Teaching and Supervision
- Media
- 2022 UNSW Research Infrastructure Scheme, Faculty Infrastructure Project 'Mouse Haematology Analysis Platform'
- 2022-2027 2021/MRF2014748 MRFF Rare Cancers Rare Diseases Unmet Need 'A Platform trial of combination precision guided therapies for high-risk childhood cancer (OPTIMISE)'
- 2022-2025 2021/TPG2112 Cancer Institute NSW Translational Program Grant'Improving outcomes for children and young adults with sarcoma'
- 2021-2024 EPCDRI2006645 NHMRC Childhood Cancer Research (MRFF)'Improving outcomes for children with high risk cancer'
- 2021-2022 MRFF Frontier Health and Medical Research Program 'Australian Centre for E3 Therapeutics – ACE3T'
- 2020-2024 MRFF Emerging Priorities and Consumer Driven Research initiative EPCD000015) 'ZERO Childhood Cancer National Precision Medicine Program'
- 2020-2023 Australian Cancer Research Foundation 'The ACRF Child Cancer Liquid Biopsy Program'
- 2020-2023 Neuroblastoma Australia ‘MYC inhibitors to potentiate CART cell therapy
- 2020-2023 Cancer Australia/ The Kids Cancer Project ‘Enhanced polyamine depletion as a novel therapy for aggressive cancers
- 2019- 2021 Cancer Australia- 'Targeting the NAD pathway as a new therapeutic strategy for high-risk leukaemia in children'
- 2019- 2023 APP1159004 NHMRC Partnerships Project- 'The economic impact of precision medicine in high risk and aggressive childhood cancer'
- 2018-2022 Children’s Cancer Foundation- 'SIOPEN neuroblastoma clinical trials in Australia and New Zealand'
- 2018-2021 Children’s Cancer Foundation- 'Leveraging the SIOPEN High risk 2.0 clinical trial for high-risk neuroblastoma to understand relapse, improve residual disease detection and develop pre-clinical testing models for high-risk neuroblastoma'
- 2018 Cancer Australia/Medical Research Future Fund Australian Brain Cancer Mission- 'Zero Childhood Brain'
- 2019 Tour de Cure Foundation - 'A personalised medicine approach to the treatment of acute myeloid leukaemia in children'
- 2018 REG181200 – Cancer Institute NSW Research Equipment Grant- 'Australia’s first deformability cytometer – a novel tool for cancer mechanobiology and diagnosis'
- 2018- 2020 APP1136278 – NHMRC Development Grant- 'Multidrug Resistance Protein 1 inhibitors to sensitise cancers to chemotherapy'
- 2018- 2022 APP1132608 – NHMRC Program Grant- 'More effective therapeutic targeting of high risk childhood cancer: Neuroblastoma as a model'
Honours:
2007 Member of the Order of Australia (AM) for services to science in the field of research into childhood cancer, to scientific education and to the community
2010-12 President, Advances in Neuroblastoma Research Association.
2008 Degree of Doctor of Science, honoris causa, in recognition of eminent service to the community, University of New South Wales
2015 Inaugural Fellow, Australian Academy of Health and Medical Sciences
2020 Invited Speaker, American Association for Cancer Research, Presidential Select Symposium, San Diego, CA, USA
2020 Invitation to participate in a Voices piece on pediatric cancer for Cancer Cell
2021 Article in The Australian “Michelle Haber’s ZERO cancer mission is a world leader”
2021 Invited Keynote Speaker, DKTK (German Cancer Consortium) HARPOON (Harmonization of Reporting in Precision Oncology) Workshop (virtual event)
2022 Fellow, Australian Academy of Science
Awards:
2011 Winner - NSW Science and Engineering Award for Biomedical Sciences
2012 Winner - Cancer Institute NSW Premier’s Award for Excellence in Translational Cancer Research
2013 Finalist - NSW Health Jamie Callachor Eureka Prize for Medical Research Translation
2014 Winner - Best Translational Research Presentation, Advances in Neuroblastoma Research Congress, Cologne, Germany
2014 Winner - Cancer Institute NSW’s Premier’s Award for Outstanding Cancer Researcher of the Year
2015 Finalist - The Australian Innovation Challenge Award, for pioneering work in improving the survival rates of children with acute lymphoblastic leukaemia
2018 Finalist - CSIRO Eureka Prize for Leadership in Innovation and Science
The central focus of my research is on transforming child cancer treatment. My team is currently working on the development of new combination therapies, new methods to accurately monitor tumour progression/ evolution, and to further our understanding on the aetiology of child cancer, with potential for offering the first preventative drugs. Our aim is to enable a new era of precision medicine to significantly improve patient outcomes. Described below are some of the major projects we are currently working on:
There is a critical need for more effective and less toxic therapies for children with high-risk solid paediatric cancers such as neuroblastoma, the commonest tumour of young children. My team seek to both understand the biology of neuroblastoma and also to improve patient survival rates through (1) identifying molecular mechanism underlying drug resistance, (2) developing improved pre-clinical testing models for high-risk neuroblastoma (including patient derived xenograft (PDX) models and models of metastatic disease, and (3) modelling personalised medicine strategies including molecular profiling and ex vivo drug sensitivity screening.
Despite intensive treatment, > 50% of children with high-risk neuroblastoma still die from their disease. While anti-GD2 monoclonal antibody immunotherapy has positively impacted survival rates of patients, highlighting the potential for immunotherapeutic approaches to improve outcomes for this disease, too many high-risk patients are still dying, and hence, there is an urgent need to develop new approaches that can harness the full potential for immunotherapies in neuroblastoma treatment. The tumour microenvironment (TME) of solid paediatric cancers is often modified by the cancer cells to be immunosuppressive, allowing cancer cells to escape not only the patient’s immune system, but also potential immunotherapies. We are interested in combining immunotherapies with novel targeted agents that can reprogram the TME to be less immunosuppressive, potentially changing the treatment paradigm of neuroblastoma away from multimodal treatment protocols heavily based on cytotoxic drugs, in favour of more effective and less toxic immunotherapeutic approaches.
We have identified RUNX1T1, a transcriptional co-repressor, as a driver of childhood neuroblastoma and potentially of other high-risk child cancer. Our data strongly support the development of first-in-class RUNX1T1 inhibitors, and we are currently working on (1) identifying the key proteins that interact with RUNX1t1 that are critical for neuroblastoma formation and progression, (2) determining the role of RUNX1t1 in the progression of other high-risk childhood cancers, and (3) developing RUNX1t1 inhibitors for progression into clinical trial.
My team and I have pioneered four novel therapeutic approaches with significant clinical potential for treating the worst child cancers with particularly poor outcomes, namely, high-risk neuroblastoma; high-grade brain tumours (e.g., Diffuse Intrinsic Pontine Glioma (DIPG)); high-risk/relapsed Acute Lymphoblastic and Myeloblastic Leukaemia; and aggressive sarcomas. These approaches include (1) polyamine inhibition with DFMO/AMXT-1501, (2) targeting the epigenome with CBL0137, (3) inhibiting arginine metabolism with BCT-100, and (4) NAMPT inhibition with OT-82. While each of these therapies have progressed to clinical trial, we are currently working on increasing their clinical potential by incorporating them into optimal combinations for each tumour type which will then be incorporated into our ZERO Childhood Cancer basket trial program and other international trials. We are also working on defining biomarkers to identify the patients most likely to respond, informing eligibility criteria for clinical trials and treatment choices for personalised medicine studies.
I have successfully led the development and roll-out of ZERO to every Australian paediatric oncology facility, and this program, which is currently available only to children with the most aggressive malignancies, will be made available to every child and young adult with cancer in Australia, by end of 2023. ZERO has improved outcomes for children with high-risk cancers and has transformed the approach of managing high-risk childhood cancers nationally. Currently, treatment recommendations for children enrolled on ZERO are based primarily on comprehensive whole genome sequence analysis of a single surgical biopsy of each child’s cancer. However, we know that tumours can evolve to become resistant to targeted treatments, hence requiring novel approaches to non-invasively monitor tumour mutation and progression in real time, so that we can identify developing drug resistance and change treatment in order to avoid relapse and likely death. I have pioneered a Liquid Biopsy program, involving analysis of circulating tumour DNA (ctDNA) and circulating tumour cells (CTC) in blood and other body fluids, which can harness the whole genome sequencing data from children enrolled on ZERO in order to design highly sensitive patient-specific markers which can be used to detect emergence of treatment-resistant subclones, to monitor cancer burden and the evolving mutational landscape during treatment, and hence guide personalised treatment recommendations throughout the child’s cancer journey.