The second concerns neurofilaments, the most abundant structural components in axons, and the mechanism by which they affect neuronal cell shape. The third focus is on the use of transgenic mice to investigate mechanisms of motor neuron disease. Aneuploidy, that is, the presence of an abnormal number of chromosomes, is a hallmark of many cancer cells, and may contribute to tumor development. Accurate distribution of duplicated chromosomes during cell division is a complex process, and the group studies the function of CENP-E, one of the key regulators. Data from mammalian cells, Xenopus, and Drosophila suggest that CENP-E not only links spindle microtubules to kinetochores and powers aspects of chromosome movement, but also links kinetochore capture by spindle microtubules to the mitotic checkpoint.
Cancer cells divide continuously, and many anti-cancer drugs attack dividing cells.
Taxol, for example, is thought to alter microtubule dynamics during mitosis. CENP-E, which regulates cytoskeletal changes in dividing cells, may also represent a plausible drug target. Human genetics studies and the development and analysis of mouse models are used to determine if the human and mouse homologues of the yeast genes identified play a role in suppressing cancer susceptibility. Germline mutations in human genes encoding components of the major DNA mismatch repair system cause inherited cancer susceptibility. Loss of mismatch repair function in cells leads to an increase in the rate of accumulating mutations in target genes like proto-oncogenes and tumor suppressor genes, which in turn speeds up the development of cancer.