Postgraduate research students

A major group of enzymes known as phosphodiesterases (PDEs) is essential in many biological pathways, including cell replication.  Previous research has found that a specific variant, or isoform, of PDE, family 4, subfamily D, known as PDE4D7 is reduced in aggressive prostate cancer (PCa) tumours. These tumours become resistant to typical treatment regimens that target the androgen receptor (AR), affecting 10% of patients who have taken these treatments initially. 

A new type of drug, DUBTACs, is in clinical trials as a treatment for cystic fibrosis, with results preliminarily showing reduced proteins being restored to a standard level in the lungs. Through our industry partner, Katalytic Therapeutics, Inc., new DUBTACs are being designed that will instead target the PDE proteins, particularly PDE4D7. These will be used to test the hypothesis that the aggressive form of PCa will be resensitised to AR drugs by the restoration of PDE4D7 levels, where patients would potentially take both drugs in order to see better prevention of the growth of their tumours.

In order to investigate, we will use several laboratory methods, such as western blotting, microscopy, and live cell assays, to measure cell growth and movement in response to changes in protein levels. This will be carried out using a straightforward to grow and passage cancer cell line called A549, followed by repeated experimentation in a specialised prostate cancer model that has been engineered to have reduced PDE4D7 levels, mimicking the aggressive tumours.

• Professor Will Fuller
• Professor George Baillie