DrClaireFletcher

Summary

Post-Doctoral Career Development Fellow and Prostate Cancer Foundation Young Investigator.

My principal research interests lie in the field of small RNA and post-transcriptional regulation of gene expression in human disease. Specifically, I am interested in the mechanisms through which microRNAs ‘fine tune’ gene regulation, and how aberrations in these networks may contribute to disease. I am particularly intrigued by the regulatory mechanisms that govern microRNA biosynthesis, and by the huge potential of microRNA inhibitors/mimics to act as novel therapeutics in a wide array of conditions. Further interests include: microRNA ‘signatures’ as diagnostic or prognostic biomarkers, microRNA: long non-coding RNA (lncRNA) interaction networks, regulation of gene activity through alternative polyadenylation and RNA modifications, exosomal RNA-mediated communication mechanisms, and interplay between non-coding RNAs, nuclear receptors and DNA damage in cancer.

Ongoing projects:

1.  Delineating Mechanisms of Post-Transcriptional Regulation of Wild-Type and Variant Androgen Receptors in Prostate Cancer for Therapeutic Intervention
2. Exosomal Communication Between Peri-Prostatic Adipocytes and Epithelial Cells in Obesity-Driven Prostate Cancer
3.  Kinase Modulators of MicroRNA Biogenesis
4.  Apoptosis-modulating microRNA:target networks in drug-sensitive and -resistant breast cancer
5.  Systematic Identification of MicroRNA Drivers of Resistance to Novel Therapeutics in Advanced Prostate Cancer – Exploitation as Stratification Biomarkers and Drug Targets
6.   Functional Characterisation of MicroRNAs Targeting the Androgen Receptor in Prostate Cancer
7. MiR-346: lncRNA interactions link Androgen Receptor activity and DNA repair
8.  Non-invasive microRNA signatures for predicting chemotherapy response in metastatic castration-resistant prostate cancer.

Publications:

• Fletcher CE, Sulpice E, Coombe S, Guyon L, Hamilton M, Chrysostomou S, Leach D, Sharp A, Welti J, Yuan W, Dart DA, International SU2C/PCF Prostate Cancer Dream Team, Swain A, Lupold S, De Bono JS, McGuire SE, Gidrol X and Bevan C (2018). A Novel High-Throughput Screening Approach Identifies Androgen Receptor-Modulatory MicroRNAs and New Therapeutic Targets in Prostate Cancer  (submitted)
• Fletcher CE (2017). AR-v7 liquid biopsy for treatment stratification in prostate cancer: how close are we? Current Opinion in Urology 27(5):500-509
• Fletcher CE, Godfrey JD, Shibakawa A, Bushell M and Bevan CL (2017). A Novel Role for GSK3β as a Modulator of Drosha Microprocessor Activity and MicroRNA Biogenesis. Nucleic Acids Res. Mar 17; 45(5): 2809–2828
• Fletcher CE, Dart DA and Bevan CL (2014): Interplay between Steroid Hormones and MicroRNAs: Implications for Hormone-Dependent Cancers. Endocrine-Related Cancer 21(5): R409-429.
• Sita-Lumsden A^#, Fletcher CE^#, Dart DA, Brooke GN, Waxman J, Bevan CL (2013). Circulating nucleic acids as biomarkers of prostate cancer. Biomarkers in Medicine 7(6): 867-877. (^# - joint first authors)
• Frampton AE, Fletcher CE, Gall TMH, Krell J, Castellano L, Bevan CL, Stebbing J (2013): Circulating peripheral blood mononuclear cells exhibit altered miRNA expression patterns in pancreatic cancer. Expert Review Molecular Diagnostics 13(5): 425-430
• Fletcher CE, Dart DA, Sita-Lumsden A, Cheng H, Rennie P and Bevan CL (2012): Androgen-regulated processing of the oncomir, miR-27a, which targets Prohibitin in prostate cancer. Hum. Mol. Genet. 21(14):3112-27.

 

Book Chapter:

• Bevan CL, Fletcher CE, Sita-Lumsden A and Shibakawa A (2015, in press). Chapter 28: Circulating Nucleic Acids as Prostate Cancer Biomarkers. In: Garcia-Giménez JL ed. Epigenetic Biomarkers and Diagnostics. Elsevier.

 

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