陳光超老師實驗室

蛋白質酪氨酸去磷酸酶在發育與腫瘤發生的功能研究

蛋白質酪氨酸去磷酸酶(Protein Tyrosine Phosphatases, PTPs)是一群受到嚴密調控的酵素， 並且在各種不同的過程中與蛋白質酪氨酸磷酸酶(Protein Tyrosine Kinase, PTK)協同控制蛋白質的磷酸化。目前許多的證據指出，在腫瘤發生及個體發育過程當中，蛋白質磷酸化的調控扮演重要的角色。我們使用PTPome 作為研究PTP在癌症及發育的一個模式，並利用質譜為基礎的受質捕獲方法找尋dPtpmeg/PTPN3酪氨酸去磷酸酶的潛在受質。遺傳與生化實驗分析指出，dPtpmeg和PTPN3分別能調節果蠅和哺乳動物細胞中表皮生長因子受體酪氨酸蛋白激酶受質15(Eps15)的酪氨酸磷酸化狀態。表皮生長因子受體（EGFR）屬於酪氨酸激酶受體家族，參與在調節細胞的存活，增殖，分化，遷移和腫瘤發生。我們探討PTPN3在表皮生長因子受體訊息傳導的分子調控機制及在表皮生長因子受體相關的非小細胞肺癌形成的角色。這項研究的結果對於表皮生長因子受體所導致腫瘤，提供具潛力的新治療干預措施。

細胞自噬作用(Autophagy)訊息傳遞網路之功能研究

細胞自噬作用(Autophagy)為調控細胞存活與凋亡的重要機轉。當個體細胞遇到生存壓力時，會自行發展出包膜企圖吞食或分解胞內的物質，以保全細胞 存活的自我保護機制。近年來科學家也發現，細胞自噬作用與生物發育以及許多人類疾病，例如腫瘤、感染與免疫、及神經退化性疾病密切相關。藉由生化與分子遺傳實驗我們最近的研究發現一新的Atg9膜蛋白調控之訊息傳遞路徑。利用氧化壓力下的果蠅腸道細胞為模式系統，我們發現Atg9會與腫瘤壞死因子受體相關因子(dTRAF2/TRAF6)結合作用，活化JNK訊息傳遞及啟動下游的氧化壓力防護機制，包含細胞自噬、細胞凋亡、以及促進幹細胞增生。另外，我們更進一步發現受氧化壓力活化的細胞自噬會透過負回饋機制抑制JNK訊息傳遞，避免防護機制過度活化，以維持在氧化壓力下組織的恆定性。這些研究成果可能提供治療細胞自噬失調和氧化壓力等相關疾病新的思考方向。

經歷

• 2013 – 迄今   副研究員, 中央研究院生化所
• 2013 – 迄今   合聘副教授, 臺灣大學生化科學研究所
• 2007 – 2013   兼任助理教授, 臺灣大學生化科學研究所
• 2006 – 2012   助研究員, 中央研究院生化所
• 1998 – 2005   博士後研究, 美國麻州總院癌症研究中心及哈佛大學醫學院

學歷

• 1997   博士, 分子遺傳, 美國德州大學奧斯汀分校

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