Development of novel prognostic test for cancer

Applications are invited for a self-funded, 3 year full-time or 6 year part-time PhD project.

The PhD will be based in the School of Medicine, Pharmacy and Biomedical Sciences and will be supervised by Prof Darek C Gorecki (School of Medicine) and Dr Giuseppe Banna (QA University Hospital).

Developing a reliable cancer prognostic test would profoundly impact patient management by enabling therapy intensity to be tailored—improving survival rates while avoiding potential overtreatment. However, the histological complexity within a single cancer type, compounded by extensive molecular heterogeneity among patients, and further exacerbated by inflammation and the diverse tumor-surrounding stroma, has impeded efforts to identify prognostically relevant indicators or molecular markers.

We found that DMD gene expression correlates with patient survival across different tumor types (doi.org/10.3390/cancers15051378). The DMD is the second largest and widely expressed human gene, which generates a plethora of functionally distinct isoforms. It could be compared to a Swiss Army knife, with various "business heads" (variants) sharing a common handle. Unsurprisingly, up- and down-regulation of DMD variants in cancers is functionally important.

Indeed, we identified specific DMD gene transcript variants, which expression levels strongly correlated with patients’ survival across histologically-diverse mesotheliomas (doi: 10.21037/tlcr-24-28) and sarcomas (manuscript in preparation). We also demonstrated that these specific variants play significant roles in tumour cells, as CRISPR/Cas ablation resulted in significantly more aggressive behavior of malignant cells (DOI: 10.1093/hmg/ddae094).

This PhD projects aims at the development of a clinically-applicable prognostic cancer test. It will involve retrospective analysis of archival primary tumour samples for the expression levels of specific DMD transcripts, and correlation of these with patients’ survival data. Moreover, new biopsy and intra-operational samples will be analyzed for a prospective study. The levels of transcripts expression will be correlated with diverse clinicopathological data to identify key features affecting tumour progression and predict patient-specific risk levels. For this integration, an AI tool will be developed (a project aligned but outside of this PhD). Moreover, the role of specific variants will be studies in malignant cells in vitro by ablating their expression using CRISPR/Cas9. 

The PhD researcher involved in this project will receive comprehensive training in cancer biology, equipping them with an in-depth understanding of the mechanisms underlying tumor development and progression. In addition, will gain proficiency in a diverse set of molecular and cellular techniques, including but not limited to, advanced gene editing, transcriptomic analysis, and cell culture methodologies. This hands-on experience will be complemented by training in data analysis and interpretation, enabling the researcher to contribute meaningfully to the field of biomarkers in oncology. The PhD researcher would be given an opportunity to attend the mesothelioma clinic to familiarize with contemporary treatments and clinical trials with novel anticancer agents.

Fees and funding

Visit the research subject area page for fees and funding information for this project.

Funding availability: Self-funded PhD students only. 

PhD full-time and part-time courses are eligible for the UK Government Doctoral Loan (UK and EU students only – eligibility criteria apply).

Bench fees

Some PhD projects may include additional fees – known as bench fees – for equipment and other consumables, and these will be added to your standard tuition fee. 

How to apply

We’d encourage you to contact Prof Gorecki  (darek.gorecki@port.ac.uk) to discuss your interest before you apply, quoting the project code.

When applying please quote project code: PHBM5381025