• 基因調控
• 遺傳學

• 美國奧勒岡州立大學生化暨生物物理博士

1. 低氧細胞訊息傳遞系統在細胞分化與胚胎發育上所扮演的功能：當細胞面臨低氧的壓力時，會透過細胞內的一套低氧訊息傳遞系統，調整細胞內的生理活性以適應所面臨的環境壓力。當細胞內的有效氧含量低於正常呼吸作用所需的氧濃度時，便會啟動訊息傳遞系統，增加細胞質內低氧誘發蛋白（HIF）的濃度，進入細胞核內開啟各種生理適應相關基因的表現，改變細胞內的呼吸、代謝、生長活性，並且刺激增加紅血球與血管新生的能力，藉以提高體內氧氣運送的效率。雖然我們對於一般生物適應低氧環境壓力的生理調適已有一定程度的了解，但是究竟在正常生長環境中，這些低氧訊息系統在生物體內所扮演的其他生物功能以及物種間對低氧壓力的耐受性的演化差異仍所知有限。目前我們與校內外多位老師合作，從生化、代謝、細胞、發育、遺傳、基因/蛋白體學等不同角度探討細胞低氧訊息系統在細胞分化與胚胎發育上所扮演的功能，並且從分子演化的角度去探討生物物種間對低氧逆境的生理適應的個別差異。
2. 內生性與外源性低氧壓力對胚胎發育的影響：由於低氧訊息傳遞系統在胚胎發育的過程中扮演非常重要的功能，因此我們目前正著手探討胚胎發育過程中啟動低氧訊息傳遞的機制以及外在環境的低氧壓力對胚胎發育產生影響。
3. 鯉魚對低氧環境壓力的特殊生理調適機制：在硬骨魚類中，鯉魚以及其他相近的鯉科魚種（如鯽魚、金魚）對於低氧環境具有異常的耐受能力，這與其高效率的造血能力有關。當面臨缺氧的環境時，鯉魚會大量製造紅血球，以增加體內氧氣的供應。過去的研究指出鯉魚在正常的生長環境下，其消化道不斷吸收與累積鋅離子，儲存在腸內的纖維母細胞，而當面臨低氧的緊迫環境時，這些貯存的鋅離子會被釋放出來，透過血液的循環，藉由運鐵蛋白（transferrin）運送到腎臟造血系統，刺激紅血球的大量生成。為了探討鯉魚的這個特殊生理機制，我們目前與多位老師共同合作，分別從分子、細胞與演化的層次，利用基因體學、蛋白體學、分子遺傳學以及生物資訊分析等方式來探討鯉魚低氧適應的生理機制與系統演化的路程。

基因選殖，轉殖基因，胚胎顯微注射，基因表現定性/定量分析，生物資訊分析

1. Wang, W.D., Chen, Y.M., Hu, C.H.* (1998). Detection of Ah receptor and Ah receptor nuclear translocator mRNAs in the oocytes and developing embryos of zebrafish ( Danio rerio). Fish Physio. Biochem 18, 49-57.
2. Hu, C.H.*, Wang, J.M., and Tseng, H.B. (1998). The first high-mobility-group box of upstream binding factor assembles cross-over DNA junction by basic residues. Biochem J 333, 51-56.
3. Hsu, T.*, Huang, H.M., and Hu, C.H. (1998) Differential effects of heavy metals on the binding of Xenopus upstream binding factor (xUBF) to DNA. Chemosphere 36,2367-2373.
4. Wang, W.D., Wu, J.C., Hsu, H.J., Kong, Z.L., and Hu, C.H.* (2000) Overexpression of a zebrafish ARNT2-like factor represses CYP1A transcription in ZLE cells. Mar Biotechnol 2, 376-386.
5. Hsu, Y.L.*, Wang, K.H., Yang, Y.H., Tung, M.C., Hu, C.H., Lo, C.F., Wang, C.H., Hsu, T. (2000). Diagnosis of Penaeus monodon-type baculovirus by PCR and by ELISA of occlusion bodies. Dis Aquat Org40, 93-99.
6. Hsu,H.J., Wang, W.D., and Hu, C.H.*. (2001). Ectopic expression of negative ARNT2 fact disrupts fish development. Biochem Biophys Res Commun 282, 487-492.
7. Sen, A., Hu, C.H., Urbach, E., Wang-Buhler, J.L., Yang, Y.H., Aric, E., Buhler, D.R. (2001) Cloning, sequencing and characterization of CYP1A1 cDNA from leaping mullet ( Liza saliens) liver and implications for te potential functions of its conserved amino acids. J Biochem Mol Toxicol 15, 243-255.
8. Wen, H.J., Wang, Y., Chen, S.H., and Hu, C.H.* (2002) Expression pattern of the single-minded gene in zebrafish embryos. Mech Dev 110, 231-235.
9. Wang, W.D., Wang, Y., Wen, H.J., Buhler, D.R., and Hu, C.H.* (2004) Phenylthiourea as a weak activator of aryl hydrocarbon receptor inhibiting 2,3,7,8-tetrachlorodibenzo-p-dioxin-induced CYP1A1 transcription in zebrafish embryo. Biochem Pharmacol 68, 63-71.
10. Chung, W.G., Sen, A., Wang-Buhler, J.L., Yang, Y.H., Lopez, N., Merrill, G.F., Miranda, C.L., Hu, C.H., Buhler, D.R. (2004) cDNA-directed expression of a functional zebrafish CYP1A in yeast. Aquat Toxicol 70, 111-121.
11. Tseng, H.P., Hseu, T.H., Buhler, D.R., Wang, W.D., and Hu, C.H.* (2005) Constitutive and xenobiotics-induced expression of a novel CYP3A gene from zebrafish larva. Toxicol Appl Pharmacol 205, 247-258.
12. Wang-Buhler J.L., Lee S.J., Chung W.G., Stevens J.F., Tseng H.P., Hseu T.H., Hu C.H., Westerfield M, Yang Y.H., Miranda C.L., Buhler D.R.. (2005) CYP2K6 from zebrafish (Danio rerio): Cloning, mapping, developmental/tissue expression, and aflatoxin B1 activation by baculovirus expressed enzyme. Comp Biochem Physiol C 140: 207-219.
13. Corley-Smith G.E., Su H.T., Wang-Buhler J.L., Tseng H.P., Hu C.H.*, Hoang T, Chung W.G., Buhler D.R.* (2006) CYP3C1, the first member of a new cytochrome P450 subfamily found in zebrafish (Danio rerio). Biochem Biophys Res Commun 340, 1039-1046.
14. Huang H.C., Hu C.H., Tang M.C., Wang W.S., Chen P.M., Su Y.* (2006) Thymosin 4 triggers an epithelial–mesenchymal transition in colorectal carcinoma by upregulating integrin-linked kinase. Oncogene 26, 2781-2790.
15. Chen, S.Y., Hsieh, C.S., Chu, S.W., Lin, C.Y., Ko, C.Y., Chen, Y.C., Tsai, H.J., Hu, C.H., and Sun, C.K. (2006). Noninvasive harmonics optical microscopy for long-term observation of embryonic nervous system development in vivo. J Biomed Opt 11, 054022.
16. Hsieh, S.L., Ruan, Y.H., Li, Y.C., Hsieh, P.S., Hu, C.H., Kuo, C.M. (2008). Immune and physiological responses in Pacific white shrimp (Penaeus vannamei) to Vibrio alginolyticus. Aquaculture 275, 335–341
17. Yin, H.C., Tseng, H.P., Chung, H.Y., Ko, C.Y., Tzou, W.S., Buhler, D.R., and Hu, C.H. (2008). Influence of TCDD on zebrafish CYP1B1 transcription during development. Toxicol Sci 103, 158-168.
18. Hsieh, S.L., Ko, C.Y., Chen, S.Y., Liu, T.M., Wu, J.S., Hu, C.H., Sun, C.K. (2008). In vivo long-term continuous observation of gene expression in zebrafish embryo nerve systems by using harmonic generation microscopy and morphant technology. J Biomed Opt 13, 064041.
19. Chen CM*, Chen CC, Shih TH, Pai TW, Hu CH, and Tzou WS (2010) Efficient algorithms for identifying orthologous simple sequence repeats of disease genes. J Syst Sci Complex 23, 906-916.
20. Chuang CS, Pai TW*, Hu CH, Tzou WS, Chang MDT, Chang HT, Chen CC (2011) Functional pathway mapping analysis for hypoxia-inducible factors,” BMC Syst Biol 5S1, S3, DOI: 10.1186/1752-0509-5-S1-S3.
21. Ko CY, Tsai MY, Tseng WF, Cheng CH, Huang CR, Wu JS, Chung HY, Hsieh CS, Sun CK, Hwang SPL, Yuh CH, Huang CJ, Pai TW, Tzou WS, and Hu CH* (2011) Integration of CNS survival and differentiation by HIF2α. Cell Death Differ 18, 1757-1770.
22. Chen FP*, Hu CH, and Wang KC (2013) Estrogen modulates osteogenic activity and estrogen receptor mRNA in mesenchymal stem cells of women. Climacteric 16, 154-160.
23. Chang CT, Chung HY, Su HT, Tseng HP, Tzou WS, and Hu CH*(2013) Regulation of Zebrafish CYP3A65 Transcription by AHR2. Toxicol Appl Pharmacol 270, 170-184.
24. Chung HY, Chang CT, Young HW, Hu SP, Tzou WS, Hu CH* (2013) Ethanol inhibits retinal and CNS differentiation due to failure of cell cycle exit via an apoptosis-independent pathway. Neurotoxicol Teratol 38, 92-103.
25. Chen CM*, Shih TH, Pai TW, Liu ZL, Chang MDT, Hu CH (2013) Gene expression rate comparison for multiple high-throughput datasets. IET Syst Biol 7, 5S1, 135-142. DOI: 10.1049/iet-syb.2012.0060.
26. Chen CM, Pai TW*, Chuang CS, Huang JL, Tzou WS, Hu CH (2014) Identifying significant associations of orthologous simple sequence repeats with gene ontologies. Int J Data Min Bioinform 9, 37-51.
27. Tzou WS*, Chu Y, Lin TY, Hu CH, Pai TW, Liu HF, Lin HJ, Cases I, Rojas A, Sanchez M, You ZY, Hsu MW (2014) Molecular evolution of Mmultiple-level control of heme biosynthesis pathway in animal kingdom. PLoS One 9, e86718. DOI: 10.1371/journal.pone.0086718.
28. Tzou WS*, Lo YT, Pai TW, Hu CH, Li CH (2014) Stochastic simulation of Notch signaling reveals novel factors that mediate the differentiation of neural stem cells. J Comput Biol 21, 548-567.
29. Lin TY, Chou CF, Chung HY, Chiang CY, Li CH, Wu JL, Lin HJ, Pai TW, Hu CH, Tzou WS* (2014) Hypoxia-inducible factor 2 alpha is essential for hepatic outgrowth and functions via the regulation of leg1 transcription in the zebrafish embryo. PLoS One 9, e101980 . DOI: 10.1371/journal.pone.0101980 .
30. Chen CM, Sio, CP, Lu YL, Chang HT, Hu CH, Pai, TW* (2014) Identification of conserved and polymorphic STRs for personal genomes. BMC Genomics 15-S10, S3. DOI:10.1186/1471-2164-15-S10-S3.
31. Lien HW, Yuan RY, Chou CM, Chen YC, Hung CC, Hu CH, Hwang SP, Hwang PP, Shen CN, Chen CL, Cheng CH, Huang CJ* (2016) Zebrafish cyclin Dx is required for development of motor neuron progenitors, and its expression is regulated by hypoxia-inducible factor 2alpha. Sci Rep 6, 28297. DOI: 10.1038/srep28297