Gordon Peters : Molecular Oncology

Goals

The Polycomb group (PcG) proteins participate in the epigenetic control of gene of expression and have important roles in pluripotency, senescence and cancer. In the Molecular Oncology laboratory, we are investigating the mechanisms through which PcG proteins regulate the INK4a-ARF-INK4b tumour suppressor locus. This cluster of genes on chromosome 9p21 is the most frequent site of genetic alterations in human cancer and single nucleotide polymorphisms in the region are associated with a variety of chronic disorders, such as coronary artery disease, type 2 diabetes, late onset Alzheimers disease, as well as cancer. The three gene products, p16INK4a, p14ARF and p15INK4b, are each capable of bringing cell proliferation to a halt and their primary role appears to be the implementation of senescence, the state of permanent cell cycle arrest elicited by various forms of stress. Senescence is a front line defence against oncogenic mutations but also sets limits on normal cell proliferation and contributes to ageing.