Exploring the role of interferon stimulated genes (ISGs) in stem cells of serous ovarian cancer

Details

Epithelial ovarian cancer (EOC) is the leading cause of mortality in women due to gynaecological cancers. High-grade serous ovarian cancer (HGSOC) accounts for 70-80% of patients with EOC. Currently, in advanced HGSOC, chemotherapy with Carboplatin and Taxol is the standard treatment following surgery. More recently, chemotherapy in combination with bevacizumab or PARP inhibitors have shown a modest improvement in survival. However, the 5-year overall survival (OS) of advanced HGSOC remains at 30-45%. This is due to recurrence of disease and one of the reasons is the presence of stem cells which are resistant to conventional chemotherapy. Tumour-initiating stem cells or cancer stem cells (CSCs) cells are subset of cells that give rise to a heterogeneous population of cells similar in composition to the tumour of origin and are maintained by regulatory embryonic pathways such as Wnt/β-catenin, Notch, and Hedgehog. Our previous study has identified that the hedgehog signalling (Hh) is essential for the regulation of ovarian CSCs and blocking this pathway using small molecule inhibitors can abrogate CSCs. Interestingly, inhibiting Hh also reduced the expression of certain genes known as interferon stimulated genes (ISGs) which are usually turned on in response to a viral infection. This project will extend our research and further investigate the importance of ISGs in ovarian CSCs which can lead to the development of effective and selective treatment strategies against EOC stem-cells. This is an exciting and important research line to be pursued as ISGs could be a potential target that can be probed to effectively eradicate CSCs and achieve long term remission in ovarian cancer patients suffering from recurrent and resistant disease worldwide.

We are looking for an enthusiastic student interested in exploring how ISGs influence cancer stemness. The successful candidate will have the opportunity to develop their research skills in techniques such as:

1. Culture of different ovarian cell lines and generating CSC-enriched spheroid cultures.
2. Validating the expression profile of selected ISGs in 2D and 3D models of ovarian cancer cells using techniques including qPCR, Western blot, and immunohistochemistry.
3. Evaluating the influence of ISG expression on cancer stemness using stem cell functional assays such as single cell colony formation assay; Aldeflour assay; side population assay and the expression of CSC-specific transcription factors (Oct3/4, Sox2, Nanog and Nestin) using quantitative PCR.

How to apply

Formal applications can be submitted via the University of Bradford web site; applicants will need to register an account, select ‘Postgraduate Research’ as the type of course and then use the keywords ‘cancer therapeutics’. Applicants should then specify the project title in the ‘Research Proposal’ section.

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