The role of p53/p73 family members in the cytotoxic response

由环境、职业或治疗性暴露引起的有毒侮辱是疾病的主要原因，这些疾病的治疗对英国人口具有重大的医疗、社会和经济影响。P53蛋白家族(P53、P63和P73)被认为是脊椎动物的主要调节因子，它控制的途径从发育和内稳态功能到在癌症中的显著作用。特别是，在肿瘤发生中，p53家族功能的一个主要方面是控制细胞应激反应的能力。该实验室的总体目标是了解细胞和组织对药物、化学物质和内源性分子(如自由基)造成的伤害做出反应的基本机制。因此，利用转基因小鼠模型和高通量分析，我们的目标是研究：1)环境暴露如何驱动肿瘤进展；2)这些转录因子如何调节对毒性侮辱的反应；此外，我们致力于开发能够调节P53家族成员表达和功能的化学化合物。这可能会有潜在的治疗应用。

Toxic insult arising from environmental, occupational or therapeutic exposure, is a primary cause of disease and the treatment of these disorders has significant medical, social and economic implications for the UK population. The p53 family of proteins (p53, p63 and p73) is considered as a master regulator in vertebrates, and pathways that it controls range from developmental and homeostatic functions to the remarkable role in cancer. In particular, a predominant aspect of p53 family function in tumourigenesis is the ability to control the cellular stress response. This represents a pivotal aspect in the response to toxic insult.The overall aim of the Laboratory is to understand the fundamental mechanisms of cellular and tissue response to injury caused by drugs, chemicals and endogenous molecules, e.g. free radicals. Therefore, using both genetically modified mouse model and high throughput analysis, we aim to investigate:1) How environmental exposure drives tumour progression;2) How these transcription factors regulate the response to toxic insult;Moreover, we are dedicated to the development of chemicals compounds that can regulate expression and function of the p53 family members. This could have potential therapeutic applications.