我們以轉殖基因小鼠為模式，利用特定組織專一性的基因剔除或表現系統，廣泛地在單層柱狀上皮細胞或是複層上皮的基底細胞，誘導多個抑癌基 因(如Pten，p53,Apc,Ovca1等)缺失，同時誘導報導基因(如綠螢光蛋白基因)的表現，讓我們能夠在不同器官的柱狀上皮或 基底上皮剔除抑癌基因時，進行研究並追蹤癌症細胞的起始與進展的機制。此外，器官專一性的基因剔除系統也讓我們能更專一地探討特定的癌症 成因。我們目前對於肝癌、大腸直腸癌與攝護腺癌的疾病動物模式有成熟的分析平台，而對於胰臟癌與卵巢癌的起源細胞及其惡 化機制，亦正在積極探討 中。
The primary interests of my laboratory are to explore the molecular and cellular mechanisms that control the development of embryonic tissues/organs, the homeostasis of adult epithelial tissues, and initiation and progression of cancer. We are particularly interested in the roles of tumor suppressors p53, OVCA1 (Ovarian Cancer Gene 1), PTEN (phosphatase and tensin homolog deleted on chromosome 10) and APC (Adenomatous polyposis coli) in different cancers. To address the roles of these tumor suppressors, we create and develop different mouse genetic resources exhibiting inducible Cre recombinase in different epithelial lineages. Using genetic, biochemical and pharmacological dissection based on our established mouse models, the downstream signaling circuits that act as the key mediators during cancer progression are currently being characterized. Our research outcomes may help us to identify genes or therapeutic targets that block the carcinogenic process.
In addition, we have focused on the development of the forebrain, the heart, the thymus and the reproductive tracts in the mouse. Using different genetic modified mice, the abnormal phenotypes occurred in the mutant mice are often to be the entry points for us to explore potential mechanisms resulting in developmental defects during mammalian organogenesis.
Historically, in addition to mice, rats have been used extensively as experimental animals for biomedical research. However, compared to the very large number of genetically modified mice, there are very few mutant rats due to technology limitations. Currently, my laboratory collaborates with Dr. Richard Behringer at the M.D. Anderson Cancer Center who has established a piggyBac-mediated gene-trap mutagenesis system to create a large collection of mutant rats (Furushima et al., 2012, Genetics). The primary goal of this collaborative project is to accelerate and extend the generation of mutant rats, which may enable us to discover novel biological function of the mutated genes and to develop potential disease models in rats.
* corresponding author