Researcher

Dr Emmy Dorothee Grace Fleuren

Biography

I am a Senior Scientist with a dedication to improve outcomes for young sarcoma patients, and have over 10 years of expertise in translational sarcoma research. I recently relocated from London, UK, to join Children's Cancer Institute (CCI) and the Translational Tumour Biology group (TTB; A/Prof Paul Ekert), in which I lead an independent program focusing on sarcoma biology and the development of targeted therapeutic interventions. I am...view more

I am a Senior Scientist with a dedication to improve outcomes for young sarcoma patients, and have over 10 years of expertise in translational sarcoma research. I recently relocated from London, UK, to join Children's Cancer Institute (CCI) and the Translational Tumour Biology group (TTB; A/Prof Paul Ekert), in which I lead an independent program focusing on sarcoma biology and the development of targeted therapeutic interventions. I am also the appointed Sarcoma Expert within the Preclinical Drug Testing Core (PDTC) and ZERO Childhood Cancer Program, and hold a Conjoint Senior Lecturer Appointment at the University of New South Wales (UNSW). Personalised medicine, combination therapies, phosphoproteomics and sarcomas affecting the young are my key focus areas. I further have extensive experience in in vitro and in vivo drug testing of paediatric sarcoma models and a strong background in oncogenic signal transduction. 

 

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 identification of activated drug targets not identified with ZERO's current molecular platform in paediatric sarcoma patients

 

  • Pinpoint mechanism-of-action and predictive biomarkers for drugs with molecularly unexplained extraordinary responses in paediatric sarcoma models

 

We have a range of exciting student projects available, and I very much encourage enthusiastic students to contact our lab to discuss the opportunities (efleuren@ccia.org.au). 

 


My Grants

 



 

  • 2020, AI, Research Grant - ANZSA Xavier K Foundation
  • 2020, CIB, Pioneering Research Grant – Tour de Cure
  • 2020, CI, Two-year project grant: Emerging Research Leader Program – CanToo
  • 2016, CITwo-year Rubicon Fellowship - Netherlands Organisation for Scientific Research (NWO) 
  • 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:

• 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 (supervision dr. Emmy Fleuren and dr. Ashleigh Fordham)

2. Explaining unexplained drug responses in childhood sarcomas (supervision dr. Emmy Fleuren and dr. Ashleigh Fordham)

3. Exploiting aberrated DNA damage signaling signatures to identify personalised combination therapies for paediatric cancer treatment (supervision dr. Emmy Dolman and dr. Emmy Fleuren)

 

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)!

 

 

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Publications

by Dr Emmy Dorothee Grace Fleuren

ORCID as entered in ROS

Videos

CanToo Grant - Thank you and brief introduction to sarcoma research