Role of Stem Cells in Tumour Initiation

Supervisor:  Prof Ahmed Ashour Ahmed

An exciting opportunity for a DPhil studentship in the Nuffield Department of Obstetrics & Gynaecology, is available at the Ovarian Cancer Cell Laboratory, MRC Weatherall Institute of Molecular Medicine (WIMM) to investigate the genetic basis of acquisition of stem cell properties in ovarian cancer.

World wide, almost 220,000 women are newly diagnosed with ovarian cancer every year and out of these about 150,000 die within 5 years of diagnosis. This makes ovarian cancer the most lethal gynaecological tumour. Late diagnosis is a key contributing factor to this high fatality. The poor understanding of the potential cell of origin and the natural history of tumour initiation has made it difficult to identify effective screening tests in ovarian cancer. Our laboratory has identified key early changes in ovarian cancer that may contribute to stem cell regulation and tumour initiation.

Stem cells are capable of self-renewal and differentiation. The balance between these two processes is precisely controlled. Cancer cells can also self-renew, although in a poorly controlled fashion. The similarity between stem cells and cancer cells contributes to the hypothesis that the transformation of stem cells may leads to neoplasia. It is possible that the acquisition of stem cell properties in differentiated cells may be a critical first step in the process of transformation. This project aims to test this hypothesis. Specifically, the candidate will test the effect of perturbed expression of genes that are know to be involved in driving stem cell differentiation on the susceptibility to cancer transformation. Comparison between the genomes and transcriptomes of normal stem cells and ovarian cancer cells will be made to identify key genes that are likely to be involved in stem cell regulation in ovarian cancer.  The role of these putative genes will be investigated by genomic and epigenomic editing in adult epithelial cells and in stem cells to test their potential contribution to oncogenesis. In addition, appropriate in vivo animal models will be used to test the hypothesis.

Training opportunities:

The candidate will be encouraged to develop scientific independent thinking and to develop ideas and hypotheses that could be tested experimentally. The work will involve training in key bioinformatic approaches to generate hypotheses that could then be tested using functional genetics. Clustered regularly interspaced short palindromic repeats  (CRISPR) technology will be utilised for editing the genomes of cells to study the functional consequences of specific somatic mutations.

The laboratory currently has several experienced postdoctoral fellows in addition to research assistants, clinical research fellows and students. The postdoctoral fellows and the PI will provide daily support and supervision of the student when needed. In addition to collaborative opportunities at the WIMM, our laboratory has established collaborations with research groups at the Nuffield Department of Obstetrics and Gynaecology, the Structural Genomics Consortium, the Dunn School of Pathology and the Gray Institute for Radiation Oncology and Biology. The candidate will be expected to participate in the weekly laboratory meetings and fortnightly journal clubs and encouraged to present research at national and international meetings.

For further information, please contact:  Prof Ahmed Ahmed