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Tumor biology, targeted therapy, biomarker, cell cycle, centrosome and signal transduction
We are interested in mechanisms involved in maintaining genetic integrity. We use cell and molecular biology approaches to identify and characterize key regulators of the processes of mitosis, centrosome duplication, and DNA damage repair. We are developing new cancer therapeutics that target these regulatory molecules, including survivin, which is over expressed in a variety of human cancers. Our on-going work is to demonstrate the proof-of-principle that targeting survivin can be used as a strategy to treat human malignancy. We are presently undertaking a new project to investigate the role of SUN domain-containing proteins in DNA damage response and tumorigenesis. We have solved the crystal structure of the SUN domain of the human SUN2 protein, which provides the molecular basis for further understanding the biological functions of the SUN2 complex.
We are also interested in the mechanism of drug resistance. The ErbB receptors, such as EGFR and HER2, contribute to breast, ovarian and lung cancer development. Although drugs targeting the ErbB molecules have been used clinically with some success, a major problem is that many patients who are initially responsive to ErbB-targeted therapies experience recurrence and become refractory to the therapies. Our recent studies indicate that abnormalities of survivn-mediated mitotic checkpoint, as well the Hippo-YAP signaling pathway, may render cancer cells resistance to a variety of cancer drugs. YAP activation is also associated with malignant transformation and cancer stem cell phenotype. Understanding the functional interactions between the ErbB and Hippo-YAP pathways may provide insights into new therapeutic opportunities for the treatment of human cancers.