DrClaire Fletcher
Associate Professor of Molecular Oncology
Department of Surgery & Cancer - Faculty of Medicine
Orcid identifier0000-0003-2083-2798 (opens in a new tab)
- Associate Professor of Molecular OncologyDepartment of Surgery & Cancer - Faculty of Medicine
- 020 7594 2821 (Work)
- ICTEM building, Hammersmith Campus, United Kingdom
RESEARCH
Research within the Fletcher lab encompasses several overlapping themes:
i) Delineating mechanisms of obesity-driven PC aggressiveness
Obesity will shortly overtake smoking as the largest modifiable cancer risk-factor and rates of obesity are rising globally. Further, high-fat diet is linked with increased risk of PC death, and volume of peri-prostatic adipose tissue (PPAT) with increased risk of lethal PC/reduced therapy-response. This theme examines bi-directional communication between adipocytes and PC cells to develop novel therapeutics. We have established a biobank of matched urine, whole blood, plasma, prostatic (PPAT) and non-prostatic adipose (NPAT), tumour tissue and clinicopathological date from >100 PC patients. We developed a pipeline for routine PPAT primary culture, and generated immortalised pre-adipocyte cell lines lean/obese PC patient PPAT and NPAT. Protocols for in vitro pre-adipocyte differentiation/immortalisation were developed, and manipulation of key PPAT EV-modulated genes shown to have therapeutic potential in advanced disease.
ii) Non-canonical mechanisms of miR-mediated gene regulation
Our previous research showed that a specific microRNA induces potent, rapid, transcription-dependent and genome-wide DNA damage in PC cells through association with key DNA replication and transcription factors, without impacting non-cancerous prostate cells. It induces tumour regression and synergises with DNA-damaging therapeutics. We are exploring its use as a targeted mCRPC therapeutic and conducting further detailed investigations into its mechanism(s) of action.
iii) Post-transcriptional regulation of gene activity in prostate cancer
Additional research projects focus on transcript length alterations during prostate cancer progression using large patient data sets, the role of lncRNA, NORAD, in PC chemotherapy response, CRISPR screening to identify unique vulnerabilities of drug-resistance prostate cancer, and the role of miRs as 'master regulators' of cell cycle progression.
i) Delineating mechanisms of obesity-driven PC aggressiveness
Obesity will shortly overtake smoking as the largest modifiable cancer risk-factor and rates of obesity are rising globally. Further, high-fat diet is linked with increased risk of PC death, and volume of peri-prostatic adipose tissue (PPAT) with increased risk of lethal PC/reduced therapy-response. This theme examines bi-directional communication between adipocytes and PC cells to develop novel therapeutics. We have established a biobank of matched urine, whole blood, plasma, prostatic (PPAT) and non-prostatic adipose (NPAT), tumour tissue and clinicopathological date from >100 PC patients. We developed a pipeline for routine PPAT primary culture, and generated immortalised pre-adipocyte cell lines lean/obese PC patient PPAT and NPAT. Protocols for in vitro pre-adipocyte differentiation/immortalisation were developed, and manipulation of key PPAT EV-modulated genes shown to have therapeutic potential in advanced disease.
ii) Non-canonical mechanisms of miR-mediated gene regulation
Our previous research showed that a specific microRNA induces potent, rapid, transcription-dependent and genome-wide DNA damage in PC cells through association with key DNA replication and transcription factors, without impacting non-cancerous prostate cells. It induces tumour regression and synergises with DNA-damaging therapeutics. We are exploring its use as a targeted mCRPC therapeutic and conducting further detailed investigations into its mechanism(s) of action.
iii) Post-transcriptional regulation of gene activity in prostate cancer
Additional research projects focus on transcript length alterations during prostate cancer progression using large patient data sets, the role of lncRNA, NORAD, in PC chemotherapy response, CRISPR screening to identify unique vulnerabilities of drug-resistance prostate cancer, and the role of miRs as 'master regulators' of cell cycle progression.
GRANTS
- STANDARD - CALLMRC UKRI IAA 22-25Medical Research Council (MRC)1 Apr 2022 - 31 Mar 2027