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Searching for biomarkers of pre-cancer lesions associated with pancreas cancer

  • Full or part time
    Prof K M Ryan
  • Application Deadline
    Monday, August 26, 2019
  • Funded PhD Project (European/UK Students Only)
    Funded PhD Project (European/UK Students Only)

Project Description

Pancreatic adenocarcinoma (PDAC) is a cancer that usually presents as an advanced disease. At the point of diagnosis, 50% of patients already have metastatic lesions and a further 35% have locally advanced disease. PDAC is also refractory to many existing forms of therapy, so survival rates are very low. The median survival after diagnosis is 4-5 months with only 5% surviving 5 or more years. Importantly, it is also predicted that PDAC will become the 2nd biggest cause of cancer-associated death by 2030. It is therefore critical that we develop strategies to detect PDAC at an early stage and ideally even before it develops.

It is the aim of this project to identify a biomarker to detect the precursors of PDAC which are known as pancreatic intraepithelial neoplasia (PanIN). The student will work closely with a Postdoctoral Scientist on a mouse model lacking autophagy (a process of cellular digestion that preserves cell viability), which develops exacerbated numbers of PanIN (see Nature 2013, below). Samples will be taken from these animals and will be analysed by mass spectrometry to identify proteinaceous, metabolic and microRNA factors that are altered when compared to wild-type animals. Further validation will include other mouse models and human samples. This important and challenging project will also utilize cutting-edge technologies to identify the pathways affected by the identified factor(s) and to understand how they contribute to the development of PanIN and PDAC.


To apply, and for further details on the application process, please click on the ‘Visit Website’ button. Please do not email your CV.

Funding Notes

This work is supported by an Early Detection Award from Cancer Research UK

References

Sierra Gonzalez, P., O’Prey, J., Cardaci, S., Barthet, V.J.A., Sakamaki, J., Beaumatin, F., Roseweir, A., Gay, D., Mackay, G., Malviya, G., Kania, E., Ritchie, S., Baudot, A.D., Zunino, B., Mrowinska, A., Nixon, C., Ennis, D., Hoyle, A., Millan, D., McNeish, I.A., Sansom, O.J., Edwards, J. and Ryan, K.M. (2018) Mannose impairs tumour growth and enhances chemotherapy. Nature 563(7733):719-723.

Sakamaki J-I., Wilkinson S., Hahn M., Tasdemir N., O'Prey J., Clark W., Hedley A., Nixon C., Long J.S., New M., Van Acker T., Tooze S.A., Lowe S.W., Dikic I. and Ryan K.M. (2017) Bromodomain Protein BRD4 Is a Transcriptional Repressor of Autophagy and Lysosomal Function. Molecular Cell 66(4):517-532

Rosenfeldt, M.T., O’Prey, J., Morton, J.P., Nixon, C., MacKay, G., Mrowinska, A., Au, A., Rai, T.S., Zheng, L., Ridgway, R., Adams, P.D., Anderson, K.I., Gottlieb, E., Sansom O.J. and Ryan, K.M. p53 determines the role of autophagy in cancer. (2013) Nature 504(7479):296-300

Liu, E.Y., Xu, N., O’Prey, J., Lao, L.Y., Joshi, S., Long, J.S., O’Prey, M., Croft, D.R., Beaumatin, F., Baudot, A.D., Mrschtik, M., Rosenfeldt, M.T., Zhang, Y., Gillespie D.A. and Ryan K.M. (2014) Loss of autophagy causes a synthetic lethal deficiency in DNA repair. Proc. Natl. Acad. Sci. (USA) 112(3): 773-8.

Long, J.S., Crighton, D., O’Prey, J., MacKay, G., Zheng, L. Palmer, T.M., Gottlieb, E. and Ryan, K.M. Extracellular adenosine sensing – a metabolic cell death priming mechanism downstream of p53. (2013) Molecular Cell. 50(3):394-406

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