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Dr Jamie Fletcher

Sch Women's&Children's Health
T: 
9385 1579
E: 
JFletcher@ccia.unsw.edu.au

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Research outline

I am an experienced researcher based at the Children’s Cancer Institute, where I lead a team of postdoctoral researchers and students focused on the childhood solid tumour neuroblastoma. Children with high-risk neuroblastoma frequently relapse with incurable, drug resistant disease, resulting in long-term survival rates below 50%. We seek to understand the biology of neuroblastoma and to improve patient survival rates through:

  • Identifying molecular mechanisms underlying drug resistance
  • Developing small molecule inhibitors targeting drug resistance mechanisms, with particular focus on multidrug resistance proteins
  • Developing improved pre-clinical testing models for high-risk neuroblastoma, including patient-derived xenograft (PDX) models and models of metastatic disease
  • Modelling personalised medicine strategies, including molecular profiling and ex vivo drug sensitivity screening

My team applies high-throughput drug screening, genomic analysis, mouse models, cell biology and tissue-culture based approaches to the study of drug resistance mechanisms, personalised medicine and new drug development in high-risk neuroblastoma. Our high-risk neuroblastoma research is published in leading journals, including JNCI, Cancer Res, Oncogene, Eur J Cancer, Nature Reviews Cancer and Science Translational Medicine.

Sample publications

Gamble LD…24 authors…Fletcher JI, Marshall GM, Ziegler DS, Hogarty MD, Burns MR, Perini G, Norris MD, Haber M (2019) Inhibition of polyamine synthesis and uptake reduces tumor progression and prolongs survival in mouse models of neuroblastoma. Science Translational Medicine 11 (477), eaau1099.

Fletcher JI, Ziegler DS, Trahair TN, Marshall GM, Haber M, Norris MD. (2018) Too many targets, not enough patients: rethinking neuroblastoma clinical trials. Nature Reviews Cancer 18(6):389-400

Murray J, Valli E, Yu DMT, Truong AM, Gifford AJ, Eden GL, Gamble LD, Hanssen KM, Flemming CL, Tan A, Tivnan A, Allan S, Saletta F, Cheung L, Ruhle M, Schuetz JD, Henderson MJ, Byrne JA, Norris MD, Haber M, Fletcher JI (2017) Suppression of the ATP-binding cassette transporter ABCC4 impairs neuroblastoma tumor growth and sensitizes to irinotecan in vivo European Journal of Cancer 83:132-141.

Jung M, Russell AJ, Liu B, George J, Liu PY, Liu T, DeFazio A, Bowtell DD, Oberthuer A, London WB, Fletcher JI, Haber M, Norris MD, Henderson MJ. A Myc Activity Signature Predicts Poor Clinical Outcomes in Myc-Associated Cancers (2017) Cancer Research 77(4):971-981

O'Brien R, Tran SL, Maritz MF, Liu B, Kong CF, Purgato S, Yang C, Murray J, Russell AJ, Flemming CL, von Jonquieres G, Pickett HA, London WB, Haber M, Gunaratne PH, Norris MD, Perini G, Fletcher JI, MacKenzie KL. (2016) MYC-Driven Neuroblastomas Are Addicted to a Telomerase-Independent Function of Dyskerin Cancer Research 76(12):3604-17.

Lau DT, Flemming CL, Gherardi S, Perini G, Oberthuer A, Fischer M, Juraeva D, Brors B, Xue C, Norris MD, Marshall GM, Haber M, *Fletcher JI, *Ashton LJ (2015) MYCN amplification confers enhanced folate dependence and methotrexate sensitivity in neuroblastoma. Oncotarget 6:15510-23.

Cheung L, Yu DM, Neiron Z, Failes TW, Arndt GM, Fletcher JI (2015) Identification of new MRP4 inhibitors from a library of FDA approved drugs using a high-throughput bioluminescence screen. Biochemical Pharmacology 93:380-8.

Cheung L, Flemming CL, Watt F, Masada N, Yu DM, Huynh T, Conseil G, Tivnan A, Polinsky A, Gudkov AV, Munoz MA, Vishvanath A, Cooper DM, Henderson MJ, Cole SP, Fletcher JI, Haber M, Norris MD. (2014) High-throughput screening identifies Ceefourin 1 and Ceefourin 2 as highly selective inhibitors of multidrug resistance protein 4 (MRP4). Biochemical Pharmacology 91:97-108.

Fletcher JI, Gherardi S, Murray J, Burkhart CA, Russell A, Valli E, Smith J, Oberthuer A, Ashton LJ, London WB, Marshall GM, Norris MD, Perini G, Haber M (2012) N-Myc regulates expression of the detoxifying enzyme glutathione transferase GSTP1, a marker of poor outcome in neuroblastoma. Cancer Research 72(4):845-853.

Fletcher JI, Haber M, Henderson MJ, Norris MD (2010) ABC transporters in cancer: more than just drug efflux pumps. Nature Reviews Cancer 10, 147-56.

Fletcher JI, Meusburger S, Hawkins CJ, Riglar DT, Lee EF, Fairlie WD, Huang DCS, Adams JM (2008) Apoptosis is triggered when pro-survival Bcl-2 proteins cannot restrain Bax. Proceeding of the National Academy of Sciences USA 105, 18081-18087.

Willis SN, Fletcher JI, Kaufmann T, van Delft MF, Chen L, Czabotar PE, Ierino H, Lee EF, Fairlie WD, Bouillet P, Strasser A, Kluck RM, Adams JM, Huang DC (2007) Apoptosis initiated when BH3 ligands engage multiple Bcl-2 homologs, not Bax or Bak. Science 315, 856-859.

Qualifications: 

Bachelor of Medical Science (Hons.), University of Sydney

PhD, University of Sydney

Grants: 

Current research support

Children’s Cancer Foundation; 2019–2022; $671,271; 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

NHMRC Project Grant; 2018–2020; $660,005; Precision medicine for high-risk neuroblastoma (APP1146817)

NHMRC Development Grant; 2018–2020; $840,166; Multidrug Resistance Protein 1 inhibitors to sensitise cancers to chemotherapy (APP1136278)

Neuroblastoma Australia; 2018–2020; $65,000; Characterization of high-risk neuroblastoma models to support translational research

Neuroblastoma Australia; 2018–2019; $66,140; Optimization of high-risk neuroblastoma model development

Awards: 

UNSW ARC Postgraduate Council Supervisor Award 2018

UNSW Faculty of Medicine Dean’s Rising Star Award 2011

Children's Cancer Institute Award 2011

Cancer Institute NSW Career Development & Support Fellowship 2010

Balnaves Foundation Young Researcher’s Fund Award 2008

NHMRC Peter Doherty Fellowship 2000

Keywords: 
cancer
paediatric oncology
multidrug resistance
anticancer drug development
personalised medicine
animal models
preclinical drug evaluation
neuroblastoma
tumour biology
circulating tumor cell
drug screening assays
Research
Field of Research (FOR) Tag: 
Cancer Cell Biology
Socio-economic Objective (SEO) tags: 
Cancer and Related Disorders
Teaching & Supervision
I am available to supervise: 
Yes
Areas of supervision: 

Potential honours and PhD projects

  • Inhibition of Multidrug Resistance Proteins as a therapeutic strategy in paediatric and adult cancers
  • Modelling personalised medicine strategies in high-risk neuroblastoma
Supervision keywords: 
cancer
nervous system cancers
drug resistance
anticancer drugs
Media & Expertise
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