Overview
Mitosis is structurally the most dynamic phase of the cell cycle, as sister chromatids are irreversibly segregated to daughter cells. Defects in mitotic spindle assembly and in the checkpoints that normally maintain the fidelity of this process can lead to chromosomal instability and cancer. The fidelity of chromosome segregation is monitored by mitotic checkpoints that delay entry into mitosis until all of chromosomes have made correct attachments to spindle microtubules. During this complex process, protein kinases play important roles in promoting or retarding transitions between different stages and checkpoints of the cell cycle. We aim to further understand mitotic control and use this information to identify and validate mitotic regulators as targets for cancer therapy.
Our focus
The research of the Cancer Drug Target Discovery laboratory has focused on the mitotic kinases Aurora-A and Mps1. Aurora-A kinase has been found to be amplified in more than 50% of primary colorectal cancers and up to 20% of primary breast tumours as well as in breast, ovarian, colon, prostate, and cervical cell lines. Mps1 is a mitotic checkpoint kinase. Increased Mps1 expression has been found in multiple different types of human cancers including breast cancer. The over-expression of these kinases and the association with genetic instability in tumours has made these genes attractive targets for anticancer drug discovery.
