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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. If kinetochores are not attached to microtubules, they generate signals that prevent the cell cycle machinery from entering anaphase, a process referred to as the spindle checkpoint.

In the Stukenberg lab we study how kinetochores work and how they are regulated. Surprisingly we found that a single complex, known as the Ndc80 complex, is central to both the motor and signaling roles of the kinetochore. 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 initiate the spindle checkpoint signal and turn it off after microtubules attach.

We also study the Aurora B kinase. 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.

There are three areas of research in the lab

Kinetochore structure and function 

Aurora B kinase regulation of kinetochores

Dissecting kinetochore function in vitro

 

 

This page last modified 08/11/2011

The Stukenberg Lab and the Burke Lab are in the Department of Biochemistry and Molecular Genetics at the University of Virginia