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  Targeting the Microtubule Cytoskeleton in Cancer Therapy

Epithelial lung cancer cells in interphase, stained for tubulin (green) and DNA (blue).

Our laboratory's overall research theme encompasses the study of the microtubule cytoskeleton of cells and the anti-tumor drugs that target microtubules. Our research is focused on developing an understanding of the molecular mechanism(s) of action of these drugs and of resistance to them, as well as the little-understood functional consequences of drug-induced microtubule disruption and cell death. Microtubules are unique in that they fill the entire cytoplasm from just outside the nucleus all the way to the plasma membrane, providing ample surface for protein-protein interactions; and also in that they have inherent polarity, allowing for the directional flow of information within the cell. As a result, small molecules that target microtubules will disrupt all of these interactions and signal cascades, in addition to affecting mitosis.

Of particular interest to us is the study of the transcription factors, proteins, and signaling pathways that are critically involved in cancer, whose function depends on functional interphase microtubules, as they may be downstream targets of the drugs that disrupt microtubules. We are also studying the molecular basis of drug resistance to microtubule-targeting drugs and the role of the cytoskeleton in the regulation of protein translation. Our laboratory uses functional cellular and molecular biology assays coupled with high-resolution microscopy and live-cell imaging to gain new information on microtubule and cancer-related systems and their cellular regulation. This information can be used to explain and improve the clinical function of anti-cancer drugs.

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