I did my undergraduate degree in Biomedical Science which involved a year in industry where I worked for the University of Sheffield to perform laboratory experiments on clinical trial samples (cardiovascular unit). I undertook a masters degree at the University of Sheffield which included a large lab project. I ended up applying for a PhD in the lab I was in for my MSc. I was interested in this PhD not only because I knew the people and lab were great, but cancer biology is particularly interesting to me and something I deem to be incredibly important.
Progastrin is a precursor form of the stomach hormone gastrin. Unlike gastrin, progastrin binds to a novel gastrin binding receptor, rather than the classical CCKB-receptor, however this interaction and downstream effect remains to be characterised. Progastrin has been implicated to have anti-apoptotic and proliferative effects on cells and is regularly found up-regulated in a variety of tumour patients (You et al, 2020), particularly that of gastric origin. Furthermore, despite it is increasingly being reported that targeting progastrin could be useful in cancer therapies (Chauvel et al, 2017), progastrin’s mechanisms of action still remain unclarified.
Gastric cancer is the third leading cause of cancer-related mortality worldwide largely due to a lack of targeted therapy, therefore characterisation of signalling mechanisms involved in progastrin’s tumorigenic effects is essential for the generation of potential therapeutic strategies for patients with gastric cancers, or other progastrin-expressing tumours.
The aims of this study are to develop a model to study progastrin signalling in and to characterise the downstream signalling mechanisms of progastrin. Furthermore, this project also aims to identify the involvement of annexin A2, a calcium dependent membrane binding protein, which has been reported to act as a novel progastrin receptor (Singh et al, 2012).
It is hoped that by improving the understanding of progastrin signalling, it will allow further research into potential therapeutic targets for use in gastric cancer combination therapy, such as alongside the proprietary drugs developed by TYG Oncology for classical gastrin signalling in tumours (Tyg Oncology, 2020).