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Epigenetic regulation of cholangiocarcinoma growth


   Radcliffe Department of Medicine

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  Prof D Kerr  No more applications being accepted  Self-Funded PhD Students Only

About the Project

Cholangiocarcinoma (CCA) is a rare malignant bile duct tumour with an average incidence of 1/100,000 in the population per year. The overall incidence of CAA includes 15% of primary liver cancers, the second most common type of primary liver cancer. The majority of which are inoperable and resistant to chemotherapy; at present the 5-year survival rate is less than 5%. Therefore, there is an urgent need to identify novel molecule mechanisms that drive this malignancy and to facilitate the development of targeted therapies.

We have recently investigated the role of ubiquitin specific peptidase (USP) molecules in CCA growth. We demonstrated that USP rewired the tumour development programme by modifying oncogenes and the tumour survival signalling pathways. Essentially, epigenetic modulation plays a crucial role in regulating the progression of CCA, maintaining oncoprotein histone structures to prevent tumour cell from apoptosis and sustain the cell survival.

To unravel mechanisms by which USP epigenetically determine CCA growth, the approaches of epigenetic chemical probes, the CRISPR library screening, and artificial intelligent will be employed for this study. Outcomes of these investigations will enable us to identify biomarkers and drugs for CCA therapy. 

The student will acquire expertise in a wide range of state-of-the-art molecular and cell biological techniques, deep machine learning and bioinformatics analysis; consequently, providing an excellent foundation for a research career.  Formalised training and assessment of each technique by our members of the laboratory as appropriate. Our laboratory has clearly defined protocols to support training in specific experimental techniques. Standard operating procedures are regularly updated to ensure that methods are optimal.

The Student will also be supervised by Dr Shijie Cai.

Students are encouraged to attend the MRC Weatherall Institute of Molecular Medicine DPhil Course, which takes place in the autumn of their first year. Running over several days, this course helps students to develop basic research and presentation skills, as well as introducing them to a wide range of scientific techniques and principles, ensuring that students have the opportunity to build a broad-based understanding of differing research methodologies.

Generic skills training is offered through the Medical Sciences Division's Skills Training Programme. This programme offers a comprehensive range of courses covering many important areas of researcher development: knowledge and intellectual abilities, personal effectiveness, research governance and organisation, and engagement, influence, and impact. Students are actively encouraged to take advantage of the training opportunities available to them.

As well as the specific training detailed above, students will have access to a wide range of seminars and training opportunities through the many research institutes and centres based in Oxford.

The Department has a successful mentoring scheme, open to graduate students, which provides an additional possible channel for personal and professional development outside the regular supervisory framework. We hold an Athena SWAN Silver Award in recognition of our efforts to build a happy and rewarding environment where all staff and students are supported to achieve their full potential.


References

1 Tian Y. et al, Cell Death and Disease (2021)12:678
2 Skrede O. et al, The Lancet (2020)295:350

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