陳曜鴻（Yau-Hung Chen）

聯絡電話：(02) 2621-5656 ext.3009 傳真: (02) 2620-9924

研究室：C108

實驗室：C114、C115

E-mail: yauhung@mail.tku.edu.tw

研究專長及興趣

1.頭部肌肉與軟骨發育之分子機制探討

2.建立人類基底細胞癌(basal cell carcinoma)之魚類模式

3.抗癌金屬藥物與中草藥之篩選

4.環境毒物對於胚胎發育之影響

實驗室成員 博士後研究員： 廖勻楓 研究生： 白瓊文、傅慧娟、楊智翔、丁玉如、魏任徵、鄭凱文、李訓慈、李雅婷、陳星光 專題生： 許家豪、王瑋華、蔡伊庭、張櫂杬 畢業生

研究內容簡介

基底細胞癌(basal cell carcinoma)

基底細胞癌是最常見的皮膚癌，大約佔所有皮膚惡性腫瘤的80%以上，好發於頭臉、頸和手部。這種癌症生長緩慢而通常不會轉移到其他部位，但是若沒有處置，會局部破壞及侵犯組織，例如骨頭及神經。在基因層次方面的研究，基底細胞癌其主要成因為sonic hedgehog (shh)訊息傳遞路徑過度活化所導致的癌症。在動物模式的實驗中，以小鼠的研究為例，Oro等人(1997)將被keratin啟動子所驅動的shh基因利用基因轉殖的技術，讓shh基因專一性地在表皮組織過度表現，結果這些基因轉殖小鼠，呈現出多趾(polydactyly)、脊柱裂開(spina bifida)與一些典型的基底細胞癌的症狀，成功地重建基底細胞癌的動物模式。而這種品系的小鼠，在出生前即死亡，並不適合用來當成篩選抗癌藥物的工具。因此，我們建立了基底細胞癌的基因轉殖斑馬魚品系，以便用來開發抗腫瘤新藥。

斑馬魚當成藥物篩選平台之優點

斑馬魚(zebrafish, Danio rerio)是一種小型觀賞魚，成魚體長約3公分，好養又便宜，體積小，一般的家用一尺水族箱大約可養20隻左右，可大大地降低養殖成本。這類小型魚種擁有卵的數量多(每週可產100-300顆卵)，卵徑大而且透明，沒有產卵期的限制，體外授精，整個胚胎發育及器官形成的過程都可以直接在顯微鏡下觀察，基因轉殖操作簡單、成熟期又只有2-3個月等優點。因此，斑馬魚已成為研究癌症、心血管疾病、器官發育、脊椎動物胚胎發育、神經發育、細胞凋亡的重要模式，在藥物毒性的篩檢也扮演重要角色。斑馬魚在抗癌藥物的篩選上最大的好處是生長週期短，可以很快速、很有效率的評估療效，並且飼養成本只有小白鼠的百分之一至千分之一，非常適合藥物的篩選。

期刊論文(*corresponding author, ^#equal contribution)

(1) Chou CY*, Hsu CH, Wang YH, Chang MY, Chen LC, Cheng SC, Chen YH* (2010) Biochemical and structural properties of zebrafish Capsulin produced by Escherichia coli. Protein Expr. Purif. (in press)

(2) Chen YH*, Lin JS (2010) A novel zebrafish mutant with wavy-notochord: an effective biological index for monitoring the copper pollution of water from natural resources. Environ. Toxicol. (in press)

(3) Pai CW, Chen YH* (2010) Transgenic expression of prothymosin alpha on zebrafish epidermal cells promotes proliferation and attenuates the UVB-induced apoptosis. Transgenic Res. 19: 655-665.

(4) Peng HC, Wang YH, Wen CC, Wang WH, Cheng CC, Chen YH* (2010) Nephrotoxicity assessments of acetaminophen during zebrafish embryogenesis. Comp. Biochem. Physiol. C: Toxicol. Pharmacol. 151: 480-486.

(5) Ho MY, Chiou ML, Chang RC, Chen YH, Cheng CC* (2010) Outer membrane protein OmpF involved in the transportation of polypyridyl ruthenium complexes into Escherichia coli. J. Inorg. Biochem. 104: 614-617.

(6) Ho MY, Shieh YT, Liao CL, Chen YH, Cheng CC* (2009) Functional dihydro-1H-imidazole derivatives for MALDI signal enhancement of a lysine-specific chemical modification. J. Chin. Chem. Soc. 56: 987-994.

(7) Chen YH*, Wang YH, Yu TH, Wu HJ, Pai CW (2009) Transgenic zebrafish line with over-expression of Hedgehog on the skin: a useful tool to screen Hedgehog-inhibiting compounds. Transgenic Res. 18: 855-864.

(8) Chen YH*, Lin YT, Lee GH (2009) Novel and unexpected functions of zebrafish CCAAT box binding transcription factor (NF-Y) B subunit during cartilages development. Bone 44: 777-784. (cover article)

(9) Wang YH, Cheng CC, Lee WJ, Chiou ML, Pai CW, Wen CC, Chen WL, Chen YH* (2009) A novel phenotype-based approach for systematically screening  antiproliferation metallodrugs. Chem-Biol. Interact. 182: 84-91.

(10) Wang YH^#, Wen CC^#, Yang ZS, Cheng CC, Tsai JN, Ku CC, Wu HJ, Chen YH* (2009) Development of a whole-organism model to screen new compounds for sun protection. Mar. Biotechnol. 11: 419-429.

(11) Wu SH^#, Chen YH^#, Huang FL, Chang CH, Chang YF, Tsay HJ* (2008) Multiple regulatory elements mediating neuronal-specific expression of zebrafish sodium channel gene, scn8aa. Dev. Dyn. 237: 2554-2565.

(12) Chen YH*, Tsai HJ* (2008) Myogenic regulatory factors Myf5 and Mrf4 of fish: current status and perspective. J. Fish Biol. 73: 1872-1890. (invited review)

(13) Chen YH*, Huang YH, Wen CC, Wang YH, Chen WL, Chen LC, Tsay HJ* (2008) Movement disorder and neuromuscular change in zebrafish embryos after exposure to caffeine. Neurotoxicol. Teratol. 30: 440-447.

(14) Wang YH, Li CK, Lee GH, Tsay HJ, Tsai HJ*, Chen YH* (2008) Inactivation of zebrafish mrf4 leads to myofibril misalignment and motor axon growth disorganization. Dev. Dyn. 237: 1043-1050.

(15) Chen YH, Huang FL, Cheng YC, Wu CJ, Yang CN, Tsay HJ* (2008) Knockdown of zebrafish Nav1.6 sodium channel impairs embryonic locomotor activities. J. Biomed. Sci. 15: 69-78.

(16) Tsay HJ, Wang YH, Chen WL, Huang MY, Chen YH* (2007) Treatment with sodium benzoate leads to malformation of zebrafish larvae. Neurotoxicol. Teratol. 29: 562-569.

(17) Chen YH*, Chen WL, Wang YH, Huang MY, Chern MK (2007) Spatiotemporal expression of zebrafish D-amino acid oxidase during early embryogenesis. Fish Physiol. Biochem. 33: 73-80.

(18) Chen YH, Wang YH, Chang MY, Lin CY, Weng CW, Westerfield M, Tsai HJ* (2007) Multiple upstream modules regulate zebrafish myf5 expression. BMC Dev. Biol. 7: 1.

(19) Lin CY, Yung RF, Lee HC, Chen WT, Chen YH, Tsai HJ* (2006) Myogenic regulatory factor Myf5 and MyoD function distinctly during craniofacial myogenesis of zebrafish. Dev. Biol. 299: 594-608.

(20) Lee HC, Huang HY, Lin CY, Chen YH, Tsai HJ* (2006) Foxd3 mediates zebrafish myf5 expression during early somitogenesis. Dev. Biol. 290: 359-372.

(21) Wang SL*, Kao TY, Wang CL, Yen YH, Chern MK, Chen YH (2006) A solvent stable metalloprotease produced by Bacillus sp. TKU004 and its application in the deproteinization of squid pen for beta-chitin preparation. Enzyme Microb. Technol. 39: 724-731.

(22) Wang YH^＃, Chen YH^＃, Lu CH, Lin YJ, Chang MY, Tsai HJ* (2006) Epidermis-restricted expression of zebrafish cytokeratin II is controlled by a -141/+85 minimal promoter, and cassette -141/-111 is essential for driving the tissue specificity. Differentiation 74: 186-194.

(23) Wang YH^＃, Chen YH^＃, Lin YJ, Wu TN, Tsai HJ* (2006) A keratin 18 transgenic zebrafish Tg(k18(2.9):RFP) treated with inorganic arsenite reveals visible overproliferation of epithelial cells. Toxicol. Lett. 163: 191-197.

(24) Wang YH^＃, Chen YH^＃, Lin YJ, Tsai HJ* (2006) Spatiotemporal expression of zebrafish keratin 18 during early embryogenesis and the establishment of a keratin 18:RFP transgenic line. Gene Expr. Patterns 6: 335-339.

(25) Wang YH^＃, Chen YH^＃, Lu CH, Tsai HJ* (2005) A 23-amino-acid motif spanning the basic domain targets zebrafish myogenic regulatory factor Myf5 into nucleolus. DNA Cell Biol. 24: 651-660.

(26) Lin CY, Chen YH, Lee HC, Tsai HJ* (2004) Novel cis-element in intron 1 represses somite expression of zebrafish myf5. Gene 334: 63-72.

(27) Chen YH, Lee HC, Liu CF, Lin CY, Tsai HJ* (2003) Novel regulatory sequence -82/-62 functions as a key element to drive the somite-specificity of zebrafish myf-5. Dev. Dyn. 228: 41-50.

(28) Wang TM, Chen YH, Liu CF, Tsai HJ* (2002) Functional analysis of the proximal promoter regions of fish rhodopsin and myf-5 genes using transgenesis. Mar. Biotechnol. 4: 247-255.

(29) Chen YH, Tsai HJ* (2002) Treatment with myf5-morpholino results in somite patterning and brain formation defects in zebrafish. Differentiation 70: 447-456.

(30) Chen YH, Liang CT, Tsai HJ* (2002) Expression, purification and DNA-binding activity of tilapia muscle-specific transcription factor, MyoD, produced in Escherichia coli. Comp. Biochem. Physiol. B: Biochem. Mol. Biol. 131: 795-805; Erratum 133: 277-279, (2002).

(31) Chen YH, Lee WC, Liu CF, Tsai HJ* (2001) Molecular structure, dynamic expression and promoter analysis of zebrafish (Danio rerio) myf-5 gene. Genesis 29: 22-35.

(32) Chen YH, Lee WC, Cheng CH, Tsai HJ* (2000) Muscle regulatory factor gene: zebrafish (Danio rerio) myogenin cDNA. Comp. Biochem. Physiol. B: Biochem. Mol. Biol. 127: 97-103.

榮譽榜

1.   林永蒼、李耕琿同學之論文”Novel and unexpected functions of zebrafish CCAAT box binding transcription factor (NF-Y) B subunit during cartilages development.”發表在國際知名期刊Bone，並被選為封面故事。(2009/5/10)
 

2.   吳欣儒、楊智翔同學參加台灣水產學會2008年學術論文海報比賽，榮獲優秀壁報論文獎。(2008/12/20)
 

3.   陳韋利同學榮獲國科會全額補助，至美國麥迪遜參加斑馬魚遺傳與發育國際研討會。(2008/06/24)
 

4.   陳曜鴻老師參加SDB 66^th Annual Meeting國際研討會，榮獲SDB Teaching Faculty Travel Grant Award。(2007/06/20)

5.   張民彥同學榮獲國科會全額補助，至墨西哥參加SDB 66^th Annual Meeting國際研討會。(2007/06/20)

6.   張民彥、李耕琿、林永蒼同學參加第二十二屆生物醫學聯合學術年會，榮獲優秀壁報論文獎。(2007/03/18)

7.   李宛潔同學參加第十五屆細胞與分子生物新知研討會，榮獲優秀壁報論文獎。(2007/02/03)

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