p53 is a tumour suppressor which has a key role in regulating the stress response through its activity as a transcription factor. It protects cells from damage and helps to prevent cancer. The p53 pathway is evolutionarily conserved from flies to humans, including zebrafish and mice.
Zebrafish has historically been an excellent vertebrate model for studying embryogenesis. An increasing number of cancer researchers now consider zebrafish a promising model system to study tumourigenesis in vivo. We have characterised the fundamental zebrafish p53 response to different stress and drug treatments, including changes at the transcriptional level, at the translational level and to the localisation of ZFp53 and its newly identified isoform, delta113p53. The downstream genes involved in the p53 pathway in zebrafish are also under careful study. These data have formed the basis for our using zebrafish to perform drug screens.
We are also using transgenic reporter zebrafish and mice to study p53 activity.
P53 is lost or mutated in many tumours. Restoration of p53 activity is key to the success of cancer therapy, but it can cause toxic side effects in normal healthy tissue. Our animal models will enable us to maximize the therapeutic effects while minimizing cytotoxicity, thus optimizing drug treatment regimens.
Taken together, these in vivo studies will enable us to better understand cancer mechanisms and to design better therapies to treat human disease.