Louise Baxandall

• Msci Biomedical Genetics
• Targeting the WIP1/PPM1D Oncoprotein for potentiation of p53-dependent therapies in neuroblastoma

My project focused mainly on the WIP1 protein. WIP1 is coded for by the oncogene PPM1D and is transcriptionally driven by p53 forming a negative autoregulatory feedback loop to suppress p53. During my project I was primarily based in tissue culture where I studied NGP and N20R1 neuroblastoma cell lines; neuroblastoma was chosen because as WIP1 is often abnormally present in many copies in neuroblastoma. I was aiming to find out whether WIP1 inhibitors potentiate the effects of MDM2 inhibitors, which are an effective cancer treatment as MDM2 is another protein that acts to supress p53 in an autoregulatory feedback loop. I did this by performing drug matrixes on my two cell lines that showed the effects of various concentrations of WIP1 inhibitor GSK2830371 and MDM2 inhibitor RG7388 both as solo treatments and in combination with each other.

Funding source: Newcastle University
Project Supervisor: Professor John Lunec