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Investigating the role of the dual action PRH/HHEX tumour suppressor protein/oncoprotein in cancer biology.


   Division of Cancer and Stem Cells

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  Prof K Gaston, Dr Sheela Jayaraman  Applications accepted all year round  Self-Funded PhD Students Only

About the Project

The PRH/HHEX protein is a transcription factor that functions as a tumour suppressor protein in some types of cancer, including breast cancer and prostate cancer (Gaston et al, 2016: Kershaw, et al 2017). However, this protein functions as an oncoprotein in other cancer types, such as bile duct cancer (Kitchen et al, 2019). The PRH/HHEX gene is therefore a proto-oncogene with tumour-suppressor function (Shen et al., 2018). Less than 100 such dual action oncoprotein/tumour suppressor proteins have been identified to date and we need to know more about these proteins are involved in tumourigenesis.

The aim of this project is to determine how the PRH/HHEX protein can function in such different ways depending on the cell type in which it is expressed and its expression level.  In this project we will:

(1) Measure PRH/HHEX protein levels in cancer tissues using immunohistochemistry.

(2) Compare the genes that are regulated by PRH/HHEX in different cell types using RNA sequencing and chromatin immunoprecipitation sequencing.

(3) Identify PRH/HHEX interacting proteins in different tissues using proteomics.

These experiments will increase our understanding of the role of PRH/HHEX in cancer and this could result in new approaches to cancer treatment.

Please include in your application:

·      A detailed CV;

·      Names and addresses of three referees;

·      A covering letter highlighting your research experience/capabilities;

·      At the top of your letter please put the name of your proposed supervisor and the title of the research


Funding Notes

We will consider applications from self-funded prospective students with:
• a good biomedical or related degree, with interests in any of the areas outlined above,
• a good command of the English language (written and spoken) as outlined in the postgraduate prospectus,
• competence with computers and data handling,
• a source of funding to cover tuition fees and bench fees (note that tuition fees are different for Home and EU students than for International students). More information regarding fees can be found under the ‘Medicine’ heading at: https://www.nottingham.ac.uk/fees/tuitionfees/202021/pgrcourses202021.aspx#Medicine
To be considered for this studentship, please apply online at: https://www.nottingham.ac.uk/pgstudy/course/research/Medicine-PhD

References

Gaston, K., Tsitsilianos, M.A., Wadey K., and Jayaraman P.-S. (2016) Misregulation of the proline rich homeodomain (PRH/HHEX) protein in cancer cells and its consequences for tumour growth and invasion. Cell and Bioscience. 6:12.
Kershaw, R.M., Roberts, D., Wragg, J., Shaaban, A.M., Humphreys, E., Halsall, J., Price, L., Bicknell, R., Gaston, K., and Jayaraman P.S. (2017) Proline-Rich Homeodomain protein (PRH/HHEX) is a suppressor of breast tumour growth. Oncogenesis, 6:e346.
Kitchen P, Lee KY, Clark D, Lau N, Lertsuwan J, Sawasdichai A, Satayavivad J, Oltean S, Afford S, Gaston K, and Jayaraman P.S. (2019) A runaway PRH/HHEX-Notch3 positive feedback loop drives cholangiocarcinoma and determines response to CDK4/6 inhibition. Cancer Research, 80:757-770.
Shen, l., Shi, Q and Wang, W.(2018) Double agents: genes with both oncogenic and tumor-suppressor functions. Oncogenesis, 7:25.
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