The aim of my research program is to understand the mechanism by which chromosomes are segregated at mitosis. Segregation is effected by the action of the mitotic spindle, a large, dynamic array of microtubules that generates the force and directionality for chromosome movement. Mitosis is a critical step in the cell cycle. Mistakes in chromsome segregation give rise to chromosome abnormalities, and play an important role in causing birth defects and in the progression of cancer cells to a metastatic phenotype. Drugs that interfere with mitosis are important anti-cancer agents. We use a combination of biochemical, pharmacological and microscopic methods to probe mitotic mechanism. We use tissue culture cells and Xenopus egg extracts as model systems. Our mainfocus is on understanding the role of microtubules in mitosis, and identifying and determining the function of other proteins that interact with microtubules during mitosis. A new focus in the lab is to use novel small, chemically synthesized molecules to interfere with mitosis. Massspectrometry will be used in two important ways: 1)Analysis of proteins and peptides. We often need to identify proteins we have purified in very small amounts (less than 10pmol). Mass spectrometry is the most sensitive method. We also need to determine if some proteins are phosphorylated or otherwise modified. Again, mass spectrometry is the most definitive method. 2) We are increasingly interested in synthesizing new small molecules to find potential drug-like compounds that interfere with mitosis. We also synthesize fluorescent probes. Mass spectrometry willbe used to check the structure of synthetic compounds. The compound classes that currently interest us are mainly aromatic in structure, so NMR is of limited utility for structural determination. Mass spectrometry is essential for unambiguous structural determination, and it has the benefit of high sensitivity.
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