Our Research
Defects in chromosome segregation can generate aneuploidy, a condition that is found in almost all human tumors and is a major cause of miscarriages and birth defects. The complex process of chromosome segregation must be highly coordinated to ensure fidelity and prevent aneuploidy. Kinetochores are central players in mitosis. Kinetochores are complex protein machines that assemble on each chromatid. They link chromosomes to microtubules and are the motors that move chromosomes on the mitotic spindle. Kinetochores also ensure that all chromatids are attached before they are segregated, by generating signals that prevent the cell cycle machinery from entering anaphase, a process referred to as the spindle checkpoint.
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In the Stukenberg lab we study how kinetochores function and how they are regulated. Surprisingly, we found that the Ndc80 complex both binds microtubules for the spindle and is required to generate spindle checkpoint signals. We are intensively studying this fascinating group of four proteins. These studies are determining how the kinetochore uses the energy stored within a microtubule to perform the work of moving chromosomes. In addition, we are determining how kinetochores generate the spindle checkpoint signal and turn it off after microtubules attach.
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We also study the Chromosome Passenger Complex that has the Aurora B kinase as its catalytic component. Aurora B regulates kinetochores and plays an important role in the spindle checkpoint. We are dissecting how Aurora B itself is regulated and identifying the important substrates that are regulated by Aurora B. Our studies are uncovering how Aurora B can coordinate numerous mitotic processes and we have found that it has an exciting role to provide spatial information for mitotic events. Since Aurora kinase inhibitors are currently undergoing clinical trials as chemotherapeutics, these studies are directing clinicians to more effectively utilize this new class of drugs.
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Xenopus S3 Cell, movie by Daum and Gorbsky
