LSI-funded PhD studentship: Developing a preventative therapy for Neurofibromatosis type 1 tumours.
Supervisors: Associate Prof Benjamin Housden, Dr. Kirsty Wan and Prof Steven West
The aim of this project is to investigate the possibility of developing a preventative treatment for tumours associated with Neurofibromatosis type 1 (NF1). This is important because patients live with the constant fear of developing disfiguring and potentially life threatening tumours throughout their lives and there are currently no effective treatments available. A preventative drug would allow patients to live without this fear and without the disfigurements caused by skin tumours. This project therefore has the potential to result in significant benefits to the quality of life of people with NF1.
NF1 tumours form when the NF1 gene is mutated in a single cell within the patient’s body. This mutation stimulates the cell to grow and divide, resulting in a tumour. Our previous work suggests that cells contain mechanisms that allow them to adapt and survive following mutation of a gene like NF1. During this project, we will look at how gene expression changes over time following loss of NF1 gene function. This approach will allow us to investigate the adaptive mechanisms to identify the genes and molecular pathways that are altered immediately following mutation of the NF1 gene. We will then test whether existing drugs, that are known to be safe for use in humans, can be repurposed to target these mechanisms. Our hypothesis is that by inhibiting these adaptive mechanisms, cells will no longer be able to survive mutation of the NF1 gene and will therefore be killed before a tumour forms.
By the end of this project, we expect to have mapped the mechanisms by which cells adapt to loss of the NF1 gene. In addition, we expect to identify existing drugs that have potential to be repurposed as a preventative therapy for NF1 tumours. By focusing on existing drugs, our results can be rapidly developed for clinical use, resulting in benefits to NF1 patients as soon as possible.