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Dr. Gorbsky:

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Cell Cycle and Cancer Biology Research Program

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OMRF finds new way to enhance cancer treatment

Gary J. Gorbsky, Ph.D. Member and Program Chair, Cell Cycle and Cancer Biology Research   Program W.H. and Betty Phelps Chair in Developmental Biology Adjunct Professor, Department of Cell Biology, University of Oklahoma Health   Sciences Center

Research Interests
Chromosome instability, the mis-segregation of chromosomes during meiosis and mitosis, is a major cause of congenital birth defects and an important contributing element in cancer malignancy. We have characterized some of the components of the cell cycle checkpoints that regulate the timing of chromosome segregation to ensure the genetic material is equally distributed to the newly formed cells during division. Our laboratory uses a combination of molecular biology and advanced imaging of living cells by microscopy to study the mechanisms of chromosome movement and how these movements influence checkpoint signaling.

The kinetochore is an organelle that forms during meiosis and mitosis at the centromeric chromatin and serves to move chromosomes and to integrate cell cycle progression. Previously, our laboratory showed that translocation of the kinetochores along microtubules is the prime mediator of chromosome movement in mitosis. We later discovered that individual kinetochores within a mitotic cell were biochemically distinct and developed the model of kinetochores as the sites where cell cycle progression through mitosis is regulated.

Currently, we are addressing the mechanochemistry of the motors that move chromosomes in mitosis and how these mechanical forces act to modulate kinase and phosphatase activities at the kinetochores of mitotic chromosomes. We have identified functions for several of the biochemical components of kinetochores including the Ndc80 protein complex and the Aurora B kinase. Recently, we discovered that the activity of another regulator, polo-like kinase-1, at mitotic kinetochores is regulated by the mechanical tension imparted by the attachment of the spindle microtubules.

In other studies we are investigating whether the defective cell cycle checkpoints of cancer cells may provide a target for the development of therapeutics that are specifically effective against tumors. Overall, we seek to understand how progression through cell division is regulated, how this regulation becomes defective in cancer cells and how these defects might be exploited to develop novel approaches in cancer therapy.

Joined OMRF Scientific Staff in 2003.

Mailing Address
Cell Cycle and Cancer Biology Research Program, MS 48
Oklahoma Medical Research Foundation
825 N.E. 13th Street
Oklahoma City, Oklahoma 73104

Contact Information
Phone: (405) 271-8168
Fax: (405) 271-7312
http://cccb.omrf.org/gorbskylab/