Supervisor View Full Details 2nd

• genetics, genomics and molecular biology
• cancer/oncology

• Pathology

• Clinical Trials
• Oncology
• Other

Molecular Diagnostics and Molecular Pathology

My laboratory concentrates on two main solid tumour types, prostate and lung cancer, within which a number of established research themes exist. My group are also involved in a number of pilot studies and clinical trials in both cancer types.

Research theme 1: Identification of inflammatory based mechanisms for Circulating Tumour Cell (CTC) immune evasion in prostate cancer.
Our hypothesis is that enhanced platelet cloaking of CTCs in obese men, due to increased systemic inflammation, is a mechanism underlying worse prognosis.

Research theme 2: non-coding RNA signatures as diagnostic and prognostic tools in prostate cancer.
The use of blood and tissue based miRNA and circRNA markers for guiding clinical decision making and stratifying patients for therapy.

Research theme 3: The application of liquid biopsies as a means to identify mechanisms of drug resistance (Prostate and Lung cancer).
Detecting blood based molecular markers in cell free DNA (cfDNA) and CTCs, to further our understanding of the development of drug resistance at a genomic level using Next Generation Sequencing (NGS).

Research theme 4: Characterisation of the immune microenvironment to stratify patients for immunotherapy in lung cancer.
Validating novel techniques to accurately detect the expression of PD-1/PDL-1 in non-small cell lung cancer (NSCLC).

Project 1: Screening the liquid biopsy for personalised therapeutic stratification of lung cancer patients (chemotherapy versus immunotherapy).

Primary Research Question: The recent success of immunotherapies in a limited cohort of NSCLC patients has again highlighted the fact that only a certain cohort of patients can be truly classified as “responders” to these treatments. In stark contrast is another patient cohort who can be classified as “super-accelerators”. Better stratification of these two groups relies on further studies investigating the patient’s individual immunological profile, tumour mutation burden (TMB) and protein expression in order to elucidate the precise molecular profile that defines responders versus super-accelerators. Development of more specific molecular signatures will allow more tailored treatments providing better responses with limited adverse effects.

Project 2: Determining the role of cirRNAs in enzalutamide resistance:

Most forms of castration-resistant prostate cancer (CRPC) are dependent on the androgen receptor (AR) for survival. While, enzalutamide provides a substantial survival benefit, it is not curative and many patients develop resistance to therapy. Although not yet fully understood, resistance can develop through a number of mechanisms, such as AR copy number gain or the generation of splice variants such as AR-V7. Circular RNAs (circRNAs) are a type of non-coding RNA that may play a role in drug resistance, through a miRNA-mediated mechanism. We have identified a circRNA signature, which is associated with enzalutamide resistance in a prostate cancer cell line model. The aim of this project is to validate this signature in patient samples and correlate with clinical outcome. The project will also further characterise the interactions between circRNAs and miRNAs, and identify possible downstream signalling pathways associated with the development of enzalutamide resistance. Additionally, CRISPER gene editing technology will be used to alter the expression of specific interconnected circRNA/miRNAs, the effects of which will be assessed using a number of functional biological assays. The data generated in this project will identify predictive biomarkers to therapy and novel therapeutic targets for CRPC.