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蔡世峰

Dr. Shih-Feng Tsai

M.D. Taipei Medical College

Ph.D. Mt. Sinai School of Medicine, City University of New York

教授 Professor

Scope of Research

I am interested in knowing how genes work, what are the genes in an organism, and how these genes, together, determine the development of an animal. Additionally, I am curious about what went wrong with gene function that had caused a human disease.

Over the past five years, my laboratory has set up large-scale, systemic approaches to analyze genes expressed in human liver. We have used state-of-art genome technologies to analyze gene expression in normal liver and liver cancer tissues. We found that protein kinase gene expression patterns are quite different between normal liver and liver cancer, and different stages of cancer might have distinct patterns of protein kinase gene expression. To build a firm basis for liver research, we have collaborated with local investigators and sequenced several thousands clones from normal liver and liver cancer cDNA libraries. This information (available at http://www.nhri.org.tw/) can be extracted to find clues to investigate pathological changes occurred during tumor formation. Recently, we built a genome sequencing laboratory to produce millions of base pairs for chromosomal regions that might have a tumor suppressor gene. This work contributed a small but visible amount to the Human Genome Project.

I think that the basic principles of how genes work are well-conserved in nature. Therefore, our laboratory has taken this idea and selected genes that are present in both human and fruit fly. We isolated several genes that might be involved in modulating chromatin structure and gene expression. The physiological functions of these genes are now under investigation.

研究工作簡介

  本人之研究興趣在探討基因之功能,特別是一個生物個體的許多基因,如何集體作用,影響生物之發育過程。另外,人類疾病與基因之關係亦為本人研究之另一重點。

  近五年來,我們對正常肝臟與肝癌組織之基因表現深感興趣,本實驗室應用先進科技,大量分析基因之表現。研究結果顯示蛋白激@在不同生理病理狀況下有不同的表現型式。我們也透過群體合作,建立研究肝臟相關研究所需之基因庫材料,針對此一目標,我們分析了數千筆肝臟之基因序列。這些資訊,可供研究者參考,從中找尋研究的新方向。最近,我們更致力建立百萬鹼基級之基因定序能力,除了協助搜尋可能之抑癌基因外,亦可對人類基因組計劃有所貢獻。

  由於基因的運作原理是演化保留下的生物基本法則,本實驗室運用此一觀念,找尋人類與果蠅共通之基因,並研究其功能。目前已發現數個基因與調節染色質結構及基因表現有關,並進一步探討其生理功能。

References:

  1. Lee, D-D., Huang, J-Y., Wong, C-K., Gagel, R. F. & Tsai, S-F. (1996) Genetic heterogeneity of familial primary cutaneous amyloidosis: Lack of evidence for linkage with the chromosome 10 pericentromeric region in Chinese families. J. Inv. Derma. 107: 30-33.

  2. Tsai, S-F., Jang, A. C.-C., Prikhod'Ko G., Bessarab, D. A., Tang, C.-Y., Pflugfelder, G. O. & Sun, Y. H. (1997) Gypsy retrotransposon as a tool for the in vivo analysis of the regulatory region of the optomotor-blind gene in Drosophila . Proc. Natl. Acad. Sci. USA. 94(8): 3837-41.

  3. Fan, F. F., Shen, H-H., Tseng, W-P., Chen, P-M. & Tsai, S-F., Molecular cloning and characterization of a human brain-specific gene implicated in neuronal differentiation. (1998) Molecular Brain Research 54: 113-123.

  4. Tsou, A.-P., Wu, K.-M., Tseng, T.-I., Chi, C.-W., Chiu, J.-W., Lui, W.-Y., Hu, C.-P., Chang, C., Chou, C.-K. & Tsai, S-F. Parallel hybridization analysis of multiple protein kinase genes: identification of gene expression patterns characteristic of human hepatocellular carcinoma. (1998) Genomics 50: 331-340.

  5. Chen YJ, Chen PJ, Shu CH, Hsu MT, Tsai SF, and Lin CH. Chromosomal Aberrations in Nasopharyngeal Carcinoma Analyzed by Comparative Genomic Hybridization (1999) Genes Chromosomes and Cancer 25:169-175.

  6. Chen, Y.-J., Yeh, S.-H., Chen, J.-T., Wu, C.-C., Hsu, M.-T., Tsai, S.-F., Chen, P.-J., & Lin, C.-H. Chromosomal changes and clonality relationship between primary and recurrent hepatocellular carcinoma. (2000) Gestroenterology 119: 431-440.

  7. Tsai, S.-F., & Chen, P.-J. The impact of human genome research on medicine -- The initial Taiwan Experience. (2000) Journal of the Formosan Medical Association 99: 107-115.

  8. Shen, H.-H., Huang, A.-M., Hoheisel. J. & Tsai, S.-F. Identification and characterization of a SET/NAP protein encoded by the brain-specific gene, MB20. (2000) Genomics 71: 21-33.
 

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