We are interested in mechanisms of chromosome segregation, defects in which lead to aneuploidy, that is, an abnormal number of chromosomes. Several common birth defects, such as Down's syndrome, result from aneuploidy arising during meiotic cell divisions. Moreover, aneuploidy arising from mitotic divisions is a hallmark of many types of solid tumors. During interphase, chromosomes are enclosed within nuclei, and exchange of all molecules between this compartment and the rest of the cell occurs through nuclear pore complexes (NPCs). Surprisingly, NPC proteins and proteins involved in trafficking of molecules into and out of the nucleus have important roles in chromosome segregation; we are investigating these roles at a molecular level. Our studies have concentrated on a GTPase called Ran and on a family of small ubiquitin-like modifiers (SUMOs), which are indispensable for mitotic chromosome segregation.
We also recently reported that the IRBIT protein is an inhibitor of ribonucleotide reductase; IRBIT works through a novel mechanism and is vital for genomic integrity.
The ultimate goals of our studies are to understand how these pathways enable accurate chromosome segregation and to discover how they are coordinated with each other and with other aspects of cell physiology.