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The research program in this laboratory is focused on: 1) the development of drugs derived from natural products, such as Taxol® and 2) the problem of drug resistance. The mechanism of action of Taxol®, a molecule that enhances the polymerization of tubulin by forming stable microtubules, is being pursued. The novel structure of Taxol®, its unique mechanism of action that was first described in this laboratory, and the positive results that have been observed in ovarian, breast and lung carcinomas have generated extensive interest in this drug. Our laboratory has used photoaffinity analogues of Taxol® to define the binding cavity for the drug within β-tubulin. The goal is to understand at a molecular level the interaction of Taxol® with the microtubule and the mechanisms by which the drug induces growth arrest and cell death in human tumors. Evidence indicates that Taxol® alters specific intracellular signal transduction events essential for drug-induced apoptosis.
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