Cancer treatment is often associated with liver injury leading to severe liver damage. A number of cancer drugs, although effective, are withdrawn from treatment and many times from the market altogether because of potential risk to liver. Hepatic safety of new cancer drugs therefore urgently requires a deeper understanding. During cancer therapy, liver injury needs to be carefully monitored for continued treatment. However, clinical monitoring is complicated as the extent of liver injuries vary depending on the type of drug, dosage and individuals. Early detection of liver injury is currently difficult because of lack of robust biomarkers. Identification of new biomarkers that can be useful for early detection and prognosis of liver injury are required and will be beneficial to all stakeholders.
In this regard, recent discovery of novel RNAs called lncRNAs, that do not code for proteins, have presented us with a large repertoire of possible biomarkers. Our work supports the hypothesis that non-coding RNAs such as lncRNAs can be effective in prediction of liver injury. However, detailed investigation of lncRNA biomarkers in cancer treatment induced liver injury has not been carried out.
The main objective of this project is to identify a lncRNA signature which can be used as biomarkers to predict liver health and its perturbation on cancer therapy. The project will employ cutting-edge transcriptomics on three major liver cell types – hepatocytes, cholangiocytes, liver sinusoidal endothelial cells. The student will analyse transcriptomics data to identify lncRNAs that can act as biomarkers of liver injury. In addition, using isolated cells from patient-derived samples and a panel of relevant cancer drugs, the candidate will conduct time-courses and dose-response to ascertain lncRNA response to drug toxicity which can be eventually translated to patient treatment.
This is an unique opportunity to work in a multi-disciplinary environment. Training gained during this PhD will help the candidate to establish a scientific career in academia as well as industry.
The supervisory team consists of Dr Kanhere, Prof Goldring and Prof Sutton. Primary supervisor, Dr Kanhere, has many years of experience in genomics and lncRNA field. Prof Goldring is a leading expert in the field of biomarkers and liver injury. Prof Sutton is well-known clinician in pancreatic and hepatobiliary field. Training and network provided by being part of DiMeN will allow the student to gain enhanced awareness of methods used in research and to contribute to the project much more meaningfully than a standard studentship. The recruited PhD student will use modern techniques in transcriptomics, molecular and cell biology approaches. The study will utilise cancer cell line models and primary patient samples. In addition to scientific training, there is ample opportunity to acquire communication and presentation skills at scientific meetings and many opportunities for publications.
Importantly, we are part of TransBioLine consortium (https://transbioline.com) which brings together leading pharmaceutical industries and academic partners to identify biomarkers that can reliably predict injuries to different organs including liver. It is highly likely that the student will have an opportunity to work with one of the industry partners from TransBioLine consortium.
Benefits of being in the DiMeN DTP:
This project is part of the Discovery Medicine North Doctoral Training Partnership (DiMeN DTP), a diverse community of PhD students across the North of England researching the major health problems facing the world today. Our partner institutions (Universities of Leeds, Liverpool, Newcastle, York and Sheffield) are internationally recognised as centres of research excellence and can offer you access to state-of the-art facilities to deliver high impact research.
We are very proud of our student-centred ethos and committed to supporting you throughout your PhD. As part of the DTP, we offer bespoke training in key skills sought after in early career researchers, as well as opportunities to broaden your career horizons in a range of non-academic sectors.
Being funded by the MRC means you can access additional funding for research placements, international training opportunities or internships in science policy, science communication and beyond. See how our current DiMeN students have benefited from this funding here: https://www.dimen.org.uk/blog
Further information on the programme and how to apply can be found on our website: https://www.dimen.org.uk/how-to-apply