Mechanisms of human cell division & organelle identity
My group is interested in how the polarization & division of human cells is regulated. Our work addresses a number of major questions about the processes needed for cell growth and division, and the consequences of dysregulation of these pathways in human cancers and other diseases.
These projects are only possible through the continued funding and support of Cancer Research UK, the Wellcome Trust and the BBSRC.
Ongoing projects in my group examine the regulation of PP1 and PP2A family protein phosphatases in dividing cells. Most recently we have explained how regulation of the PP2A-B55 phosphatases contribute important timing properties to the metaphase to anaphase transition, and identified and modelled the behaviour of key substrate proteins in the cell. A further major focus is on the mitotic kinase Aurora A & its control by protein phosphatase 6 (PP6). We have shown that this pathway is dysregulated in human cancers, and drives genome instability and DNA damage in melanoma. One future aim is to exploit this pathway to specifically target and selectively kill tumours with amplified Aurora A kinase.
Our latest work explains how altered regulation of Rab18 at the endoplasmic reticulum occurs in the severe human neurological disorder Warburg Micro Syndrome (WMS). This work links WMS to the wider family of human hereditary spastic paraplegias, many of which are also caused by altered regulation of the endoplasmic reticulum. By understanding the molecular basis of these disorders we hope to contribute to the identification of targets that can be exploited therapeutically.