Regulation of Mitosis by Aurora B Kinase
Crystal structure of the Survivin Subunit bound to the tail of Histone H3 phosphorylated on threonine 3
CPC and the centromere signaling pathway
Mitotic chromosomes are tightly regulated by ancient and highly conserved kinase and phosphate networks. We study the Aurora B kinase that controls kinetochores and cohesion of sister chromatids. Aurora B acts within a complex called the Chromosome Passenger Complex (CPC) and the other subunits control the binding of the Aurora B to chromosomes, kinetochores and spindles. The CPC is part of a Centromere signaling network and we are currently studying how this network regulates kinetochores and chromosomes and coordinates mitotic events.
How the spindle prevents and corrects improper kinetochore microtubule attachments
We have long been interested in how the centromere signaling pathways prevent and correct improper kinetochore microtubule attachments. This is a critical question since incorrect microtubule attachments may be the greatest source of aneuploidy in cells. Moreover, our analysis suggests the proteins in this pathway are all over expressed Chromosomally Instable (CIN) breast tumors suggesting that that over expression of mitotic regulators underlies CIN. We are currently focusing on the cellular mechanisms to over express the centromere signaling network and how this causes CIN.
