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黃奇英 副研究員
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| 學 歷 |
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私立東海大學 化學系 學士
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美國 愛荷華州立大學 生物化學及生物物理學 博士 |
| 經 歷 | |
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| 1994-1998 |
美國 史丹佛大學 分子藥學系 博士後研究員 |
| 1999-2003 |
財團法人國家衛生研究院 分子與基因醫學研究組 助研究員 |
| 1999-迄今 |
國防大學 生命科學研究所 副教授 |
| 2003-迄今 |
陽明大學 生物醫學技術研究所、生物藥學研究所 副教授 |
| 2003-迄今 |
台灣大學 資訊工程研究所 副教授 |
2003-2005 |
財團法人國家衛生研究院 分子與基因醫學研究組 副研究員 |
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2005-迄今 |
財團法人國家衛生研究院 癌症研究所 副研究員 |
| 榮 譽 獎 項 |
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農業研究社傑出會員 (Gamma Sigma Delta) |
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傑出研究生研究獎 ( 美國 愛荷華州立大學 ) |
| 美國 史丹佛大學 院長博士後研究獎 |
| 美國血癌研究學會獎 |
| 美國血癌研究學會 Career Development 獎 |
| 研 究 興 趣 |
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(A) Aurora-A蛋白激酶參與癌症形成及細胞分裂時期的機轉探討 Aurora-A是一個調節細胞分裂時期的serine/threonine蛋白質激酶，根據研究指出Aurora-A的功能與染色體分配(chromosome segregation)有關，引發研究學者對致癌激酶和人類癌症發展的重視。然而目前對Aurora-A參與癌症形成 (oncogenesis)及訊息傳遞(signal transduction)的機轉並不清楚。為了進一步闡明Aurora-A的作用機制，必需先找出Aurora-A可能的下游受質及交互作用蛋白質。我們利用small-pool expression screening大規模地尋找Aurora-A下游受質，並研究這些受質的生化特性。在決定Aurora-A磷酸化RalA的序列後，發現RalA在細胞內的活性與Aurora-A的表現量呈現正相關性。持續表現外源性Aurora-A與RalA會增加MDCK其細胞株的遷移能力，當同時表現Aurora-A及RalA突變基因時，則會抑制Aurora-A所誘發的遷移能力。先前研究證實Aurora-A和癌症生成極為相關，而且我們的soft agar assay也顯示，突變的RalA可以抑制Aurora-A所引發的細胞轉型(transformation)，這也意指Aurora-A可能透過磷酸化RalA來調控細胞的遷移能力。此乃第一個能夠有系統找尋Aurora-A下游可能受質的研究，提升了研究學者對Aurora-A造成癌化機轉的認知，但對於Aurora-A調控RalA訊息傳遞路徑的分子機轉至今仍待釐清。 POINT是一個蛋白質交互作用網站(http://point.bioinformatics.tw/)，
細胞質分裂可將複製的細胞一分為二，是細胞分裂末期(cytokinesis)重要的過程。而中心顆粒體(midbody)即為此時期短暫存在的類胞器，其結構是由多種蛋白質緊密結合而成，且在細胞質分裂的過程中扮演重要的角色。若中心顆粒體無法正確的調控，則將導致細胞質分裂末期無法完成，進而產生多核的細胞形態、基因組擴大等，這些都是細胞癌化的重要特色。 CRMP-1已被證實具有抑制癌轉移作用,在細胞分裂期時，CRMP-1分佈在紡綞體、中心體(centrosome)與中心顆粒體上，這與Aurora-A在細胞內的分佈有部分是重疊。進一步研究發現CRMP-1為Aurora-A的下游受質，在細胞內表現CRMP-1 shRNA或CRMP-1-AA這個無法被Aurora-A磷酸化的蛋白則會造成細胞質分裂的失敗。另外一方面，我們發現用shRNA的方法將Aurora-A 的蛋白表現量降低，也造成肺癌細胞的轉移能力降低，證實Aurora-A也是一個促進轉移的基因。目前將著重於探討在細胞質分裂時期, 轉移抑制基因和致癌基因之間的交互作用以及在cytokinesis的調控。
(B) 利用基因體學來探索肝癌及肺癌的調控機轉 藉由大量基因微陣列的資料，我們可以研究、探討許多肝癌的疾病指標以及細胞內訊息傳遞的途徑。在後基因體時代，進步的技術、工具與資訊提供了絕佳的機會去了解肝癌的成因。然而由於基因註解的不一致以及其內容難以更新，學者們通常面臨了一項艱難的考驗就是如何有效率的收集和利用這些龐大混雜的資料。我們整合生物學家以及電腦學家建立一個下一世代的資訊網絡：EHCO (http://ehco.nchc.org.tw) (Encyclopedia of Hepatocellular Carcinoma genes Online)。利用EHCO與以假設推演(如金字塔模型)的系統生物學來處理複雜的生物醫藥問題。長遠的目標是針對肝癌的研究：(1)能建立一個有系統、大規模且持續的資料收集與整合的介面，(2)能在肝癌致病機轉上辨認新的標的基因。此策略的成功將是利用網路資訊與實驗室技術結合的典範，這必能縮短治療肝癌標的尋獲的時程。此外我們完成藉由處理導致肝毒藥劑所引起肝纖維化的大鼠模式之基因微陣列圖譜(http://LiverFibrosis.nchc.org.tw:8080/LF)，鑑別出數百個可能的肝纖維化生物標記。 肺癌不論是男性或女性皆高居全世界癌症死因之第一位，在台灣不論男性或女性，肺腺癌是十分常見的肺癌。所以尋找在治療上與診斷上有意義的肺癌標記是有其重要性與急迫性。目前我們將女性肺腺癌利用基因微陣列建立大規模基因表現圖譜。也確信藉由大量基因微陣列的資料，我們可以研究、探討許多肺癌的疾病指標以及細胞內訊息傳遞的途徑。我們將強調把原始的基因微陣列資料轉變成為有用的模型，以利於更進一步了解標的基因的優先性和細胞內許多肺癌致病反應的途徑。對於這些標的基因將會利用shRNA系統來做全面性的基因剔除，以揭露標的基因導致肺癌形成的機制，以期開創新的生物醫藥研究。 |
此外，HURP在細胞分裂時期中會被磷酸化，而磷酸型HURP離開細胞分裂時期，會受到ubiquitin的調控而進行蛋白質降解作用，這結果暗示磷酸化是一種調控HURP降解的機制。細胞大量表現HURP時，即使以低血清培養細胞，仍可促進細胞在polyhema-based anchorage-independent的情況下生長。最後證據顯示，在HeLa細胞的分裂時期，Aurora-A和HURP位於細胞內的紡錘絲中心體上（spindle poles），而此結構與染色體的分配是息息相關。綜合以上的結果發現HURP是一個新的細胞週期調控者，透過對HURP的探討，進而了解Aurora-A在人類致癌機轉中所扮演的角色。目前我們藉由siRNA的技術，以闡明Aurora-A和HURP所參與訊號傳遞的路徑。
因此，了解中心顆粒體如何形成、穩定及最後如何分解以讓複製的細胞分離，將是對癌症研究領域有新的啟發。近來，有一研究團隊以蛋白質體學方式，找到了158個中心顆粒體的組成蛋白質，此研究雖未涵蓋完整的中心顆粒體蛋白質體，但已可做為我們研究中心顆粒體蛋白質交互作用網絡的基礎。我們使用POINT網站來分析各種中心顆粒體蛋白質交互作用的情形，由於這些蛋白質可能共同調節細胞質分裂的過程，因此我們可預測調控細胞質分裂的蛋白質交互作用網絡，進而了解中心顆粒體之蛋白質交互作用與癌症之間的相關性。
| 研
究 著 作 |
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| 1. | Chi-Ying F. Huang, Chiun-Jye Yuan, Nataliya B. Livanova, and Donald J. Graves.Expression, purification, characterization, and deletion mutations of phosphorylase kinase g subunit: identification of an inhibitory domain in the g subunit. Mol. Cell. Biochem. 127/128, 7-18 (1993). |
| 2. | Chiun-Jye Yuan, Chi-Ying F. Huang, and Donald J. Graves. Phosphorylase kinase: a metal ion-dependent dual specificity kinase. J. Biol. Chem. 268, 17683-17686 (1993). |
| 3. | Chi-Ying F. Huang, Chiun-Jye Yuan, Siquan Luo, and Donald J. Graves.Mutational analyses of the metal ion binding sites of phosphorylase kinase g subunit: a metal ion-dependent dual specificity kinase. Biochemistry 33, 5877-5883 (1994). |
| 4. | Chiun-Jye Yuan, Chi-Ying F. Huang, and Donald J. Graves. Oxidation and site-directed mutagenesis of sulfhydryl groups of a truncated g catalytic subunit of phosphorylase kinase. J. Biol. Chem. 269, 24367-24373 (1994). |
| 5. | Chi-Ying F. Huang, Chiun-Jye Yuan, Nataliya B. Livanova, and Donald J. Graves.Purification and characterization of truncated g1-300 subunit of phosphorylase kinase. Modern Enzymology: Problems and Trends, pp191-205 (1994). |
| 6. | Siquan Luo, Chi-Ying F. Huang, John F. McClelland, and Donald J. Graves. A study of protein secondary structures by photoacoustic infrard spectroscopy. Anal. Biochem. 216, 67-76 (1994). |
| 7. | Chi-Ying F. Huang, Chiun-Jye Yuan, Donald K. Blumenthal, and Donald J. Graves. Identification of the substrate and pseudosubstrate binding sites of phosphorylase kinase g subunit. J. Biol. Chem. 270, 7183-7188 (1995). |
| 8. | Chi-Ying F. Huang and James E. Ferrell, Jr. Ultrasensitivity in the MAP kinase cascade. Proc. Natl. Acad. Sci. USA 93, 10078-10083 (1996). |
| 9. | Chi-Ying F. Huang and James E. Ferrell, Jr. Dependence of Mos-induced Cdc2 activation on MAP kinase function in a cell-free system. EMBO J. 15, 2169-2173 (1996). |
| 10. | Chi-Ying F. Huang, Chao-Pei Betty Chang, Chia-Lin Huang, and James E. Ferrell, Jr. M-phase phosphorylation of cytoplasmic dynein intermediate chain and p150Glued.J. Biol. Chem.274, 14262-14269 (1999). |
| 11. | See-Chang Huang, Chi-Ying F. Huang, and Te-Chang Lee. Induction of mitosis-mediated apoptosis by sodium arsenite in HeLa S3 cells. Biochem. Pharmacol. 60, 771-780 (2000). |
| 12. | Wey-Jinq Lin, Yaun-Fu Chang, Wei-Li Wang, and Chi-Ying F. Huang. The mitogen-stimulated TIS21 protein interacts with a protein kinase Ca binding protein rPICK1. Biochemical J. 354, 635-643 (2001). |
| 13. | Yi-Mi Wu, Chia-Lin Huang, Hsing-Jien Kung, and Chi-Ying F. Huang*. Proteolytic activation of Etk/Bmx tyrosine kinase by caspases. J. Biol. Chem. 276, 17672-17678 (2001). |
| 14. | Chi-Ying F. Huang, Yi-Mi Wu, Chiung-Yueh Hsu,Wan-Shu Lee, Ming-Derg Lai, Te-Jung Lu, Chia-Lin Huang, Tzeng-Horng Leu, Hsiu-Ming Shih, Hsin-I Fang, Dan R. Robinson, Hsing-Jien Kung, and Chiun-Jye Yuan. Caspase activation of mammalian sterile 20-like kinase 3 (Mst3): nuclear translocation and induction of apoptosis. J. Biol. Chem. 277, 34367-34374 (2002). |
| 15. | Chiu-Ya Wang, Huey-Jing Lei, Chi-Ying F. Huang, Zhongjian Zhang, Anil B. Mukherjee, and Chiun-Jye Yuan. Induction of cyclooxygenase-2 by staurosporine through the activation of nuclear factor for IL-6 (NF-IL6) and activator protein 2 (AP2) in an osteoblast-like cell line. Biochem. Pharmacol. 64, 177-184 (2002). |
| 16. | Ann-Ping Tsou#, Chu-Wen Yang#,Chi-Ying F. Huang#, Chang-Tze R. Yu, Yuan-Chii G. Lee, Cha-Wei Chang, Bo-Rue Chen, Yu-Fang Chung, Ming-Ji Fann, Chin-Wen Chi, Jen-Hwey Chiu, and Chen-Kung Chou. Identification of a novel cell cycle regulated gene, HURP, overexpressed in human hepatocellular carcinoma. Oncogene 22, 298-307 (2003) (#contributed equally). |
| 17. | Jin-Yuan Shih, Yuan-Chii G. Lee, Shuenn-Chen Yang, Tse-Ming Hong, Chi-Ying F. Huang, and Pan-Chyr Yang. Collapsin Response Mediator Protein-1: a novel invasion-suppressor gene. Clinical and Experimental Metastasis 20, 69-74 (2003). |
18. |
Chang-Han Chen, Shen-Long Howng, Tai-Shan Cheng, Meng-Hui Chou, Chi-Ying F. Huang, and Yi-Ren Hong. Molecular characterization of human ninein protein: Two distinct subdomains required for centrosomal targeting and regulating signals in cell cycle. Biochem. Biophys. Res. Comm.308, 975-983 (2003). |
| 19. | Wei-Li Wang, Sheau-Farn Yeh, Yuan-I Chang, Shun-Fang Hsiao, Wei-Nan Lian, Chi-Hung Lin, Chi-Ying F. Huang, Wey-Jinq Lin. PICK1, an Anchoring Protein That Specifically Targets Protein Kinase Ca to Mitochondria Selectively upon Serum Stimulation in NIH 3T3 Cells. J. Biol. Chem. 278, 37705-37712 (2003). |
20. |
An-Chi Tien,Ming-Hong Lin, Li-Jen Su, Yi-Ren Hong, Tai-Shan Cheng, Yuan-Chii G. Lee, Wey-Jinq Lin, Ivan Still, and Chi-Ying F. Huang*. Identification of the substrates and interaction proteins of Aurora kinases from a protein-protein interaction model. Molecular and Cellular Proteomics 3, 93-104 (2004). |
| 21. | Fu-Hsiung Chang, Chien-Hsin Lee, Ming-Ta Chen, Chun-Chen Kuo, Yi-Lin Chiang, Chi-Ying F. Huang, and Steve Roffler.Surfection: a new platform for transfected cell arrays. Nucleic Acids Res. 32, e33 (2004). |
| 22. | Jung-Mao Hsu, Yuan-Chii G. Lee, Chang-Tze R. Yu, and Chi-Ying F. Huang*.Fbx7 functions in the SCF complex regulating Cdk1-cyclin B-phosphorylated HURP proteolysis by proline-rich region. J. Biol. Chem. 279, 32592-32602 (2004). |
| 23. | Wan-Shu Lee, Chiung-Yueh Hsu, Pei-Ling Wang, Chi-Ying F. Huang, Chia-Hua Chang, and Chiun-Jye Yuan. Identification and characterization of the nuclear import and export signals of the mammalian Ste20-like protein kinase 3. FEBS Letters 13, 41-45 (2004). |
| 24. | Cheng-Yan Kao, D. Frank Hsu, Han-Yu Chuang, Chi-Ying F. Huang, and Kuang-Chi Chen. To combine or not to combine. International Chinese Statistical Association Bulletin, 37-39 (2004). |
| 25. | Tao-Wei Huang, An-Chi Tien, Wen-Shien Huang, Yuan-Chii G. Lee, Chin-Lin Peng, Huei-Hun Tseng, Cheng-Yan Kao, and Chi-Ying F. Huang*. POINT: a database for the prediction of protein-protein interactions based on the orthologous interactome. Bioinformatics 20, 3273-3276 (2004). |
| 26. | Jiunn-Chyi Wu, Tzong-Yueh Chen, Chang-Tze R. Yu, Si-Jie Tsai, Jung-Mao Hsu, Ming-Jer Tang, Chen-Kung Chou, Wey-Jinq Lin, Chiun-Jye Yuan and Chi-Ying F. Huang*. Identification of V23RalA-Ser194 as a critical mediator for Aurora-A-induced cellular motility and transformation by small pool expression screening. J. Biol. Chem. 280, 9013-9022 (2005). |
| 27. | Chi-Chih Cheng, Shu-Mei Yang, Chi-Ying F. Huang, Jung-Chou Chen, Wei-Mao Chang, and Shih-Lan Hsu.Molecular mechanisms of ginsenoside Rh2-mediated G1 growth arrest and apoptosis in human lung adenocarcinoma A549 cells. Cancer Chemotherapy and Pharmacology 55, 531-40 (2005). |
| 28. | Te-Jung Lu, Chi-Ying F. Huang, Chiun-Jye Yuan, Yuan-Chii Lee, Tzeng-Horng Leu, Wen-Chang Chang, Te-Ling Lu, Wen-Yih Jeng, Ming-Derg Lai. Zinc ion acts as a cofactor for serine/threonine kinase MST3 and has a distinct role in autophosphorylation of MST3.J. Inorg. Biochem. 99, 1306-1313 (2005). |
| 29. | Chang-Tze Ricky Yu, Jung-Mao Hsu, Yuan-Chii Gladys Lee, Ann-Ping Tsou, Chen-Kung Chou and Chi-Ying F. Huang. Phosphorylation and stabilization of HURP by Aurora-A: implication of HURP as a transforming target of Aurora-A. Mol. Cell. Biol. 25, 5789-5800 (2005). |
| 30. | Kuang-Chi Chen, Tse-Yi Wang, Huei-Hun Tseng, Chi-Ying F. Huang and Cheng-Yan Kao. A stochastic differential equation model for quantifying transcriptional regulatory network in Saccharomyces cerevisiae. Bioinformatics 21, 2883-2890 (2005). |
| 31. | Kuo-Ting Chang, Chi-Ying F. Huang, Chun-Ming Tsai, Chao-Hua Chiu and Ying-Yung Lok. Role of IL-6 in Neuroendocrine Differentiation and Chemosensitivity of Non-Small Cell Lung Cancer.American Journal of Physiology: Lung Cellular and Molecular Physiology 289, 438-445 (2005). |
| 32. | Kuo-Ting Chang, Chun-Ming Tsai, Yih-Chy Chiou, Chao-Hua Chiu, King-Song Jeng and Chi-Ying F. Huang. IL-6 induces neuroendocrine de-differentiation and cell proliferation in non-small cell lung cancer cells.American Journal of Physiology: Lung Cellular and Molecular Physiology 289, 446-453 (2005). |
| 33. | Yong-Shiang Lin, Li-Jen Su, Chang-Tze Ricky Yu, Fen-Hwa Wong, Hsu-Hua Yeh, Su-Liang Chen, Jiunn-Chyi Wu, Wey-Jinq Lin, Yow-Ling Shiue, Hsiao- Sheng Liu, Shih-Lan Hsu, Jin-Mei Lai and Chi-Ying F. Huang. Gene Expression Profiles of the Aurora Family Kinases. Gene Expression 13, 15-26 (2006). |
| 34. | Shih-Lan Hsu, Chang-Tze Ricky Yu, Sui-Chu Yin, Ming-Jer Tang, An-Chi Tien, Yi-Mi Wu, and Chi-Ying F. Huang. Caspase 3, periodically expressed and activated at G2/M transition, is required for nocodazole-induced mitotic checkpoint. Apoptosis 11, 765-771 (2006). |
| 35. | Cheng-Ming Lee, Shih-Yin Chen, Yuan-Chii G. Lee,Chi-Ying F. Huang and Yi-Ming Arthur Chen. Benzo[a]pyrene and Glycine N-methyltransferse Interactions: Gene Expression Profiles of the Liver Detoxification Pathway. Toxicology and Applied Pharmacology 214, 126-135 (2006). |
| 36. | Li-Jen Su, Shih-Lan Hsu, Jyh-Shyue Yang, Huei-Hun Tseng, Shiu-Feng Huang, and Chi-Ying F. Huang. Global gene expression profiling of dimethylnitrosamine induced liver fibrosis: from pathological and biochemical data to microarray analysis. Gene Expression 13, 107-132 (2006). |
| 37. | He-Yen Chou, Shen-Long Howng, Tai-Shan Cheng, Yun-Ling Hsiao, Ann-Shung Lieu, Joon-Khim Loh,Shiuh-Lin Hwang,Ching-Chih Lin, Ching-Mei Hsu, Chihuei Wang, Chu-I Lee, Pei-Jung Lu, Chen-Kung Chou, Chi-Ying F. Huang and Yi-Ren Hong. GSKIP is homologous to the Axin GSK3beta interaction domain and functions as a negative regulator of GSK3beta. Biochemistry 45, 11379-11389 (2006). |
| 38. | Ya-Shih Tseng, Ching-Cherng Tzeng, Chi-Ying F. Huang, Ping-Hong Chen, Allen Wen-Hsiang Chiu, Pei-Yin Hsu, Guan-Cheng Huang, Yu-Chun Wang, Hsiao-Sheng Liu. Aurora-A overexpression associates with Ha-ras codon-12 mutation and blackfoot disease endemic area in bladder cancer. Cancer Letters 241, 93-101 (2006). |
| 39. | Te-Jung Lu, Wen-Yang Lai, Chi-Ying F. Huang, Wan-Jung Hsieh, Jau-Song Yu, Ya-Ju Hsieh, Wen-Tsan Chang, Tzeng-Horng Leu, Wen-Chang Chang, Woei-Jer Chuang, Ming-Jer Tang, Tzong-Yueh Chen, Te-Ling Lu, Ming-Derg Lai. Inhibition of cell migration by autophosphorylated mammalian sterile 20-like kinase 3 (MST3) involves paxillin and protein tyrosine phosphatase (PTP)-PEST. J. Biol. Chem. 281, 38405-38417 (2006). |
| 40. | Yuan-Chii Gladys Lee, Yu-Chyi Hwang, Kuang-Chi Chen, Yong-Shiang Lin, Dah-Yeou Huang, Tao-Wei Huang, Cheng-Yan Kao, Han-Chung Wu, Chin-Tarng Lin, Chi-Ying F. Huang. Effect of Epstein-Barr Virus Infection on Global Gene Expression in Nasopharyngeal Carcinoma. Functional and Integrative Genomics 7, 79-93 (2007). |
| 41. | Kuan-Yu Chen, Yuan-Chii Gladys Lee, Jin-Mei Lai, Yih-Leong Chang, Yung-Chie Lee,Chong-Jen Yu, Chi-Ying F. Huang*, Pan-Chyr Yang*. Identification of Trophinin as an Enhancer for Cell Invasion and a Prognostic Factor for Early Stage Lung Cancer.European Journal of Cancer (2007) (in press). (*corresponding author) |
| 42. | Chang-Han Chen, Pei-Jung Lu, Yu-Chia Chen, Shu-Ling Fu, Kou-Juey Wu, Ann-Ping Tsou, Yuan-Chii Gladys Lee, Tsu-Chun Emma Lin, Shih-Lan Hsu, Wey-Jinq Lin,Chi-Ying F. Huang* and Chen-Kung Chou*.FLJ10540-elicited cell transformation is through the activation of PI3-kinase/AKT pathway. Oncogene (2007) Jan 22; [Epub ahead of print] (*corresponding author) |
| 43. | Chun-Nan Hsu, Jin-Mei Lai, Chia-Hung Liu, Huei-Hun Tseng, Chih-Yun Lin, Kuan-Ting Lin, Hsu-Hua Yeh, Ting-Yi Sung, Wen-Lian Hsu, Li-Jen Su, Sheng-An Lee, Chan-Han Chen, Gen-Cher Lee, Der-Tsai Lee, Yow-Ling Shiue, Chang-Wei Yeh, Chao-Hui Chang, Cheng-Yan Kao, Chi-Ying F. Huang. Detection of the inferred interaction network in hepatocellular carcinoma from EHCO (Encyclopedia of Hepatocellular Carcinoma genes Online). BMC Bioinformatics (2007) (in press). |
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