Investigating the mechanisms that drive breast cancer metastasis to the brain

In recent years our understanding of the molecular basis of cancer development and evolution has improved greatly. However, there is still much to be discovered about the molecular biology that determines the spread (metastasis) of tumours to distant organs.

Breast cancers often metastasise to the brain and the prognosis for patients with breast-to-brain metastasis is very poor. There is relatively little known about which genes, and associated molecular pathways, are disrupted in cells that have the potential to metastases to, and then proliferate in, the brain.

We have been investigating the molecular basis of breast-to-brain metastasis for several years and recently carried out an exome sequencing screen to identify genes that are commonly mutated in these tumours. We believe that the gene mutations this screen identified may contribute to several processes involved in metastasis to, and eventual proliferation within, the brain.

This PhD project will investigate the role of these genes (their encoded proteins) in metastasis and investigate how loss of function mutations in these genes change cellular pathways/networks that regulate metastatic progression. 

The aim of this work is to identify prognostic markers for, and therapeutic targets against, breast tumours that may metastasise to the brain which will ultimately result in clinical benefit.

Techniques

The PhD student will gain experience in state-of-the-art biomedical research methods and techniques including gene editing, next generation sequencing techniques such as RNAseq, bioinformatic analysis, cell culture and tumour modelling, tumorigenicity assays, immunofluorescence, confocal microscopy, western blotting, flow cytometry, quantitative PCR and associated cell biology techniques.

For further information regarding the project or an informal discussion please contact Director of Studies, Dr Mark Morris  m.r.morris2@wlv.ac.uk