Industrial Partner: Philips Research (Eindhoven)
Dr Ralf Hoffmann
Project summary:
Prostate cancer becomes more difficult to treat as the disease progresses so it is important to have diagnostic tools to be able to stratify men into different risk groups. Over the last decade we have shown that a downregulation in the expression of the phosphodiesterase PDE4D7 happens in prostate cancer cells as they transition to an aggressive stage that is unresponsive to androgens. This switch increases cancer cell proliferation renders the cells insensitive to pharmaceuticals and alters the transcriptome to an androgen independent genotype. The prognostic power of PDE4D7 in metastatic PCa positions this enzyme as an attractive drug target where men at risk of deleterious biological outcomes could be given treatments to augment PDE4D7 activity. We have phenocopied aggressive PCa in the laboratory by genetically silencing PDE4D7 with siRNA in the androgen sensitive LNCaP PCa cell line which then adopt the aggressive neoplastic growth phenotype. We propose to use this cellular model to test the hypothesis that the augmentation of PDE4D7 activity (with novel peptide activators and an innovative PDE4D7 RNA vaccine) can not only reprogramme the molecular genotype and retard the aggressive growth phenotype but also resensitize the cells to currently used chemotherapies.
If successful we will trial the best treatment in an animal model of prostate cancer that is derived from our reprogrammed cells. Our ultimate goal is to develop a companion therapeutic to use alongside the prognostic power of PDE4D7 in stratifying patients into “at risk” groups.
About the Programme
This MRC programme is joint between the Universities of Edinburgh and Glasgow. You will be registered at the host institution of the primary supervisor detailed in your project selection.
All applications should be made via the University of Edinburgh, irrespective of project location. For those applying to a University of Glasgow project, your application along with any supporting documents will be shared with University of Glasgow.
How to Apply: https://www.gla.ac.uk/colleges/mvls/graduateschool/mrcdtpprecisionmedicine/howtoapply/
Please note, you must apply to one of the projects and you must contact the primary supervisor prior to making your application. Additional information on the application process is available here: http://www.ed.ac.uk/studying/postgraduate/degrees/index.php?r=site/view&id=919
For more information about Precision Medicine visit:
http://www.ed.ac.uk/usher/precision-medicine
Application Enquiries
Alexis Merry
[Email Address Removed]