細胞週期是生命過程中最基本的一個機制,其中有絲分裂的目的是產生具有相同遺傳因子的兩個子細胞。為了維持遺傳因子能正確的傳遞給子代,複製完成的染色體必須藉由複雜且嚴謹的調控機制平均的分配給兩個子細胞。我們實驗室利用分子生物學與細胞生物學的方法來研究此一過程,特別是細胞骨架與染色體結構的調控機制,有絲分裂的相關蛋白質例如 Aurora kinases 同時參予兩者的調控。我們的研究興趣在於了解Aurora kinases 與其他相關激酶(kinase)或蛋白質如何調控細胞分裂的分子機制。

Mitosis

Abnormal chromosome content, known as aneuploidy, is the most common characteristic of human solid tumors. To maintain genomic integrity, the replicated chromosomes must be equally partitioned into the daughter cells and cell cleavage (cytokinesis) should not happen until sister chromatids have been segregated to opposite poles. A class of proteins kinase termed Aurora kinases has been proposed to play an important role in the coordination of chromosomal and cytoskeletal functions in mitosis. We are interested in how these mitotic kinases coordinates with different interactors to execute cell division.

Meiosis

In mitosis and meiosis II, sister kinetochores are attached to opposite poles (biorentation). However, in meiosis I, both sister kinetochores attach to microtubules emanating from the same pole and the two sister kinetochores of each chromosome segregate to the same pole. What are the molecular factors that required for the monopolar orientation of sister kinetochores? We are using genetic and biochemical approaches to identify the key players in meiotic chromosome segregation.

Mitotic Kinase Inhibitors

Deregulated cell cycle is a common feature of cancer. The clinically used anti-mitotic drugs are taxanes and vinca alkaloids, which are so-called microtubule poisons that disrupt the mitotic spindle and induce mitotic arrest. Agents that act on mitosis specific proteins will be the alternative and promising anti-mitotic drugs. Aurora kinases are a family of serine/threonine kinases that paly an essential role in cell division. We have identified many small molecules targeting the mitotic kinases, which are potential agents for anti-tumor.

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