Laboratory of Cell Biology
The Laboratory, headed by Dr. Don Cleveland, is focused on two general areas: how chromosomes are faithfully moved into each daughter cell at cell division; and, the molecular genetics of axonal growth and mechanisms of human motor neuron disease, especially the disease, familiarly known as Lou Gehrig's disease, or ALS. The mitotic checkpoint is the cell cycle control mechanism that is the primary protection against development of aneuploidy. This is achieved by the generation at unattached centromeres of a diffusible "stop anaphase" signal. In the past year, the laboratory has identified the mechanism of activation and silencing of this essential mammalian checkpoint. Selectively weakening of the checkpoint in adult mice has allowed a test of a central question in tumor development: does aneuploidy drive carcinogenesis? A second interest is in the mechanism leading to selective killing of motor neurons in ALS. In almost every example of inherited human neurodegenerative disease, the question of selective vulnerability of individual neurons has been perplexing, since the mutant gene products are widely expressed. Using modeling in mice, an explanation has been identified: toxicity arises from the convergence of mutant damage within the target neurons and within the neighboring non-neuronal cells.
