Ph.D. Baylor College of Medicine Post-doc:Columbia University
Genome stability is maintained by intricate networks of cell cycle checkpoint proteins. In response to genotoxic stress, either extrinsic such as ionizing radiation-induced DNA breaks or intrinsic such as oxidative damage, a cascade of signaling events are initiated to arrest the cell cycle, eliminate damaged cells, or to repair the damage. Defects in these responses often lead to accumulation of mutations and development of cancers. Our studies are focused on targets of three of the checkpoint pathways involving the tumor suppressor p53 and the checkpoint kinases CHK1 and CHK2, of which mutations are associated with human cancers. Our main goals are to decipher the molecular basis of checkpoint control by these proteins, their functional relationship with DNA repair and genome maintenance, and the impacts on tumorigenesis. By using molecular approaches, cell-based and mouse models, we hope to uncover novel tumor suppressors and their modes of action, through which potential therapeutics could be devised to improve cancer treatment.
癌症的發生與基因體的變異、不穩定性息息相關，而細胞週期(Cell cycle)的調控是維持基因體穩定性的一個必要工具。在DNA斷裂、或受到氧化或其他不當修飾而改變時，細胞週期的管控機制(Checkpoint)會啟動進而促使細胞休止、凋亡、或進行修復。這些管控蛋白參與訊息傳遞、細胞反應、甚或DNA修復，在維持基因體穩定性上以及抑制癌症的產生扮演了不可或缺的角色。我們的主要研究目標在於瞭解其中三個相關的訊息傳遞途徑：(一) p53相關的路徑包括其下游所管控的標的以及它們在維持基因體穩定性上的功能；(二)管控點激酶(Checkpoint kinase) CHK1、CHK2的調控標的及作用機制；(三)這些管控機制與DNA修補機制的相互關係以及對腫瘤形成的影響。