Current Laboratory Member

Gordon K Chan, Ph.D.
Principal Investigator
Dawn Macdonald, Ph.D. Research Associate 
Devinderjit Kaur, B.Sc., M.Sc Graduate Student
Wenya Wei, B.Med Graduate Student
Cody Lewis, B.Sc., M.Sc. Graduate Student


Research Interests - Overview

In my laboratory, research is centered on the mechanism of cell cycle control and particularly the regulation of accurate chromosome segregation during mitosis. The mitotic checkpoint is a failsafe mechanism by which the cell prevents premature anaphase and ensures accurate chromosome segregation. The relevance this line of basic research to cancer is established in the demonstrated importance of chromosome fidelity during cell division to carcinogenesis. By investigating the molecular mechanism of the mitotic checkpoint, we can better evaluate these genes as potential cancer drug targets as well as contributing to the basic understanding of cancer.
 


Ongoing Research Highlights

We have three main areas of research: (i) the role(s) of the RZZ complex in mitotic checkpoint regulation and (ii) the role of the mitotic checkpoint in mitotic catastrophe (iii) mislocalization and/or overexpression of mitotic checkpoint proteins in cancers.
(i) The RZZ complex consists of three proteins, Rod, Zw10 and Zwilch. They are kinetochore proteins that recruit the microtubule motor, dynein/dynactin, to kinetochores but were found to be also essential for the mitotic checkpoint. The RZZ complex is also essential for the recruitment of the mitotic checkpoint effector Mad2 to kinetochores. The exact mechanism is still unknown. We are using molecular, biochemical and cell biological approaches to study the structure and function of the mitotic checkpoint apparatus in order to understand the underlying mechanism.
(ii) Mitotic catastrophe is a cell death phenomenon that has been observed, however, there is not a molecular marker and the mechanism of action is not known. We are following up on the findings that genotoxic drugs often results in checkpoint adaptation and ultimately mitotic catastrophe. We have observed that prolonged mitotic arrest is often accompanying mitotic catastrophe. We are examining the role of the mitotic checkpoint in this cell death process.
(iii) Mitotic checkpoint proteins are preferentially localized to kinetochores of unaligned chromosomes and kinetochore localization of key mitotic checkpoint proteins is essential for their checkpoint function. We have observed that mitotic checkpoint proteins are unable to localize to kinetochores in subsets of cancer cells. We are investigating the role of mislocalization and/or overexpression of mitotic checkpoint proteins in aneuploidy and cancers.


 
Selected Research Picture