Don W. Cleveland

University of California, San Diego

Election Year: 2006
Primary Section: 22, Cellular and Developmental Biology
Secondary Section: 24, Cellular and Molecular Neuroscience
Membership Type: Member

Research Interests

I have been interested in how accurate chromosome inheritance is achieved and how errors in this drive tumorigenesis. An initial finding was discovery of the tubulin gene families encoding the major subunits of microtubules and the first mammalian example of control of gene expression through regulated RNA instability. Components required for microtubule nucleation and anchoring during spindle assembly were identified, as well as the events activating and silencing the major cell cycle control mechanism (the mitotic checkpoint) that acts to prevent errors of chromosome segregation when cells divide. Other findings included demonstration that the extreme asymmetry of neurons is achieved with a deformable array of interlinked neurofilaments, microtubules and actin. I identified the first microtubule associated protein, tau, mutation in which was subsequently shown to cause human cognitive disease. A final contribution has been in the mechanism underlying premature death of motor neurons in inherited ALS (or Lou Gehrig's disease). This was shown to require mutant damage to both motor neurons and their neighboring supporting cells, a finding establishing stem cell replacement of non-neuronal cells as a viable therapy. Finally, a gene silencing therapy has been developed that may be broadly applicable to ALS and other major neurodegenerative diseases.

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