Research Interests: Chemoresistance in breast cancer
Nuclear Structure and Function
Epigenetic Regulation of Gene Expression
Taxanes are powerful drugs for breast cancer treatment; however, a large number of patients are resistant to this therapy for unknown reasons. Therefore it will be essential to develop prognostic tools and predictive markers to differentiate the patient population for appropriate chemotherapy selection.
This proposal aims to evaluate protein Daxx as a predictive marker for taxane response and is based on our observation that sensitivity to paclitaxel treatment, in breast cancer cell lines and mouse cells, correlates with the level of Daxx. Taxanes are reversibly binding to microtubules, thus activating transient prometaphase arrest followed by mitotic catastrophe. Our central hypothesis is that Daxx deficiency can determine resistance to paclitaxel-induced mitotic catastrophe in breast cancer patients by reversibly blocking cells in prometaphase upon treatment. Specifically, we will examine the function of Daxx as a paclitaxel sensitivity factor that can be used as a predictive marker in selection of breast cancer patients to receive taxane therapy (Aim I) and dissect the mechanism of this sensitivity elucidating the role of Daxx in mitotic progression (Aim II).
Requirements: basic cell culture, biochemistry, molecular biology lab experience required
Time Commitment: at least 15 h/week