I am a Team Leader at Children's Cancer Institute and Conjoint Senior Lecturer at the University of New South Wales with >12 years of research expertise and a dedication to improve outcomes for young patients with a difficult-to-treat type of cancer called sarcoma. In 2019, I relocated from London, UK, to join Children's Cancer Institute to set up and lead an independent program on sarcoma, and established the Sarcoma Biology and Therapeutics...view more
I am a Team Leader at Children's Cancer Institute and Conjoint Senior Lecturer at the University of New South Wales with >12 years of research expertise and a dedication to improve outcomes for young patients with a difficult-to-treat type of cancer called sarcoma. In 2019, I relocated from London, UK, to join Children's Cancer Institute to set up and lead an independent program on sarcoma, and established the Sarcoma Biology and Therapeutics group. This is Australia’s first and only research laboratory solely focussed on sarcomas affecting the young. Our mission: finding better and kinder treatments for these young patients, and make new drugs a treatment reality. We do this by strategically coupling the wealth of data generated in Australia’s national precision medicine program for children with cancer: the ZERO Childhood Cancer Program, in which I hold leadership positions (Sarcoma Subject Matter Expert, co-lead Preclinical Working Group), with innovative techniques, such as phosphoproteomics, and a robust functional validation framework. Our laboratory discoveries have already directly influenced clinical decision-making in the ZERO program, with promising clinical results. Our goal for the next years is to drive transformative contributions for more sarcoma patients.
Main research activities of my team include:
- Multi-omics characterisation of paediatric sarcoma patients within the ZERO Childhood Cancer program (linking genomics, transcriptomics and methylation profiles to in vitro, in vivo, and patient drug efficacy data)
- Evaluate phosphoproteomics for the identification of activated drug targets not identified with ZERO's current molecular platform in paediatric sarcoma patients
- Pinpoint mechanism-of-action and predictive response biomarkers for targeted drugs with extraordinary efficacies in in vitro paediatric sarcoma models that lack a known molecular response marker (“unexpected extraordinary responders”)
We have a range of exciting student projects available for all career stages (honours, PhD, BSc, MSc, ...), and I very much encourage enthusiastic students to contact our lab to discuss the opportunities (efleuren@ccia.org.au).
My Grants
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2024, CIA, Two-year project funding - Cooper Rice-Brading Foundation and Sutcliffe Family Trust
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2023, CIA, Pioneering project grant - Tour de Rocks/Tour de Cure
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2022, CIA, Pioneering project grant - Tour de Rocks/Tour de Cure
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2022, CIA, Three-year project funding - The Kids’ Cancer Project
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2021, CI, Project Grant - Tour de Rocks
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2021, CI, Three-year project funding - Cooper Rice-Brading Foundation and The Kids’ Cancer Project
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2021, CI, Three-year Early Career Fellowship - Cancer Institute NSW
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2021, CIA, Multi-year Research Grant - Anya's Wish
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2020, CIB, Research Grant - ANZSA Xavier K Foundation
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2020, CIB, Pioneering Research Grant – Tour de Cure
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2020, CI, Two-year project grant: Emerging Research Leader Program – CanToo
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2016, CI, Two-year Rubicon Fellowship - Netherlands Organisation for Scientific Research (NWO)
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2014, CIA, Research grant - Stichting HDKT
CI = (sole) Chief Investigator; CIA/B = Chief Investigator A/B; AI = Associate Investigator
My Qualifications
PhD, Medical Sciences (cum laude), 2014, Radboud University (RU), Nijmegen, the Netherlands
MSc, Biomedical Sciences (bene meritum), 2008, RU, Nijmegen, the Netherlands
BSc, Biomedical Sciences, 2006, RU, Nijmegen, the Netherlands
My Awards
2019: Early Career Researcher Travel Grant – Kids Cancer Alliance (KCA)
2019: Early Career Researcher (ECR) Rapid-fire 2nd place - KCA
2018: Travel grant – Biochemical Society
2017: Young Researcher Award - EURO EWING Consortium (EEC) and Peter Pan Charity
2016: Featured article in Nat Rev Cancer (Fleuren 2016; Nat Rev Cancer;16:83–98)
2015: Best Oncology thesis of the Netherlands and Vlaanderen 2015 – NVMO
2014: Travel grant - Dutch Cancer Society (KWF)
2011: Article and image in highlights section Clin Cancer Research (Clin Cancer Res 2011;17:7503)
My Research Activities
Publications:
- Preprint: Fordham AM, Brown LM, …, Ekert PG, Fleuren EDG. Comprehensive multi-platform tyrosine kinase profiling reveals novel actionable FGFR aberrations across pediatric and AYA sarcomas. Published online on BioRxiv preprint 21 July 2023: https://www.biorxiv.org/content/10.1101/2023.07.19.548825v1
- Lau L, Khuong-Quang DA, (+19), Fleuren EDG, (+20), Marshall GM‡, Ziegler DS‡. Precision-guided treatment improves outcomes for children with high-risk cancers. Nat Med. 2024 (online 6 June 2024)
- Brown LM, Ekert PG, Fleuren EDG. Biological and clinical implications of FGFR aberrations in paediatric and young adult cancers. Oncogene 2023;42(23):1875-1888.
- Fleuren EDG, Vlenterie M, van der Graaf WTA. Recent advances on anti-angiogenic multi-receptor tyrosine kinase inhibitors in osteosarcoma and Ewing sarcoma. Front Oncol. 2023;13(13):1013359
- van Erp AEM, …, Fleuren EDG, Versleijen-Jonkers Y, van der Graaf WTA. Targeting the FAK-Src complex in Desmoplastic Small Round Cell Tumors, Ewing sarcoma and Rhabdomyosarcoma. Sarcoma 2022; 3089424.
- Fleuren EDG, et al. Enhancing the potential of immunotherapy in paediatric sarcomas: breaking the immunosuppressive barrier with receptor tyrosine kinase inhibitors. Biomedicines 2021;9(12):1798.
- Terry RL‡, Meyran D‡, Fleuren EDG, et al. Chimeric Antigen Receptor T cell Therapy and the Immunosuppressive Tumor Microenvironment in Pediatric Sarcoma. Cancers. 2021;13(18):4704.
- Fordham AM, Ekert PG, Fleuren EDG. Precision medicine and phosphoproteomics for the identification of novel targeted therapeutic avenues in pediatric sarcomas. Biochim Biophys Acta Rev Cancer 2021;1876(2):188613
- Wong M‡, Mayoh C‡, Lau LMS‡, (+16), Fleuren EDG, (+26), Ziegler DS‡, Ekert PG‡, Cowley MJ‡. Whole genome, transcriptome and methylome profiling enhances actionable target discovery in high-risk paediatric cancer. Nat Med. 2020 Nov;26(11):1742-1753.
- van Erp AEM, …, Fleuren EDG, Versleijen-Jonkers Y, van der Graaf WTA. Olaparib and temozolomide in desmoplastic small round cell tumors: a promising combination in vitro and in vivo. J Cancer Res Clin Oncol 2020; 146:1659-1670.
- Holme H‡, Gulati A‡, Brough R‡, Fleuren EDG, et al. Chemosensitivity profiling of osteosarcoma tumour cell lines identifies a model of BRCAness. Sci Rep 2018;8(1):10614.
- van Erp AEM, Versleijen-Jonkers YMH, van der Graaf WTA, Fleuren EDG. Targeted therapy-based combination treatment rhabdomyosarcoma. Mol Cancer Ther 2018:17;1365-1380.
- Desar I, Fleuren E, et al. Systemic treatment for adults with synovial sarcoma. Curr Treat Options Oncol 2018:19;13.
- van Erp AEM, Hillebrandt-Roeffen MHS, van Houdt L, Fleuren EDG, et al. Targeting Anaplastic Lymphoma Kinase (ALK) in Rhabdomyosarcoma (RMS) with second-generation ALK inhibitor Ceritinib. Target Oncol 2017;12:815-826.
- Jones SE‡, Fleuren EDG‡, et al. ATR is a therapeutic target in synovial sarcoma. Cancer Res 2017;77:7014-7026.
- Brandsma I, Fleuren EDG, et al. Directing the use of DDR inhibitors in cancer treatment. Expert Opin Investig Drugs 2017;26:1341-1355.
- Fleuren EDG‡, Vlenterie M‡, et al. Phosphoproteomic profiling reveals ALK and MET as novel actionable targets across synovial sarcoma subtypes. Cancer Res 2017;77:4279-4292.
- Vlenterie M, Hillebrandt-Roeffen MH, Schaars EW, Flucke UE, Fleuren ED, et al. Targeting the cyclin D1 pathway in Synovial Sarcoma. Ann Surg Oncol 2016; 23:2745–2752.
- Fleuren ED‡, Zhang L‡, Wu J, Daly RJ. The kinome ‘at large’ in cancer. Nat Rev Cancer 2016;16:83–98.
- Fleuren ED et al. The role of AXL and the in vitro activity of the receptor tyrosine kinase inhibitor BGB324 in Ewing sarcoma. Oncotarget 2014;5:12753-68.
- Fleuren ED et al. Temsirolimus combined with cisplatin or bevacizumab is active in osteosarcoma models. Int J Cancer 2014;135:2770-82.
- Fleuren ED, et al. Theranostic applications of antibodies in oncology. Mol Oncol 2014;8:799-812.
- Fleuren ED et al. Targeting receptor tyrosine kinases in osteosarcoma and Ewing sarcoma: current hurdles and future perspectives. Biochim Biophys Acta - Reviews on Cancer 2014;1845:266-76.
- Fleuren ED et al. The strength of small: Improved targeting of Insulin-like Growth Factor-1 Receptor (IGF-1R) with F(ab’)2-R1507 fragments in Ewing sarcomas. Eur J Cancer 2013;49:2851-2858.
- Fleuren ED et al. Expression and clinical relevance of MET and ALK in Ewing sarcomas. Int J Cancer 2013;133:427-436.
- Fleuren ED et al. Predicting IGF-1R therapy response in bone sarcomas: immuno-SPECT imaging with radiolabeled R1507. Clin Cancer Res 2011;17:7693-703.
- Fleuren ED et al. Overexpression of the oncogenic signal transducer Gab2 occurs early in breast cancer development. Int J Cancer 2010;127:1486-92.
- Brummer T, Larance M, Herrera Abreu MT, Lyons RJ, Timpson P, Emmerich CH, Fleuren ED, et al. Phosphorylationdependent binding of 14-3-3 terminates signalling by the Gab2 docking protein. EMBO J 2008 3;27:2305-16.
My Research Supervision
Areas of supervision
Current opportunities for Honours/PhD candidates:
1. Phosphoproteomic profiling for novel target identification in childhood sarcomas (primary supervisor dr. Emmy Fleuren)
2. Explaining unexplained drug responses in childhood sarcomas (primary supervisor dr. Emmy Fleuren)
3. Exploiting aberrated DNA damage signaling signatures to identify personalised combination therapies for paediatric cancer treatment (supervision dr. Emmy Fleuren and dr. Emmy Dolman)
In all projects, the student will use a variety of molecular methodologies, including Mass-Spectrometry and targeted phosphoproteomic assays (Kinome Profiler/Western Blot/Immunohistochemistry), functional in vitro screens (drug screens/siRNA/CRISPR) and in vivo (drug efficacy) experiments. Exact techniques depend on Honours/PhD level.
If any of these subjects sound interesting to you, please do not hesitate to reach out (efleuren@ccia.org.au)!
https://orcid.org/0000-0001-6202-6861
