游正博 特聘研究員兼所長

John Yu

Distinguished Research Fellow & Director  

 2005-. Distinguished Research Fellow & Director of ICOB,Academia Sinica, Taiwan
2003-, Distinguished Research Fellow & Director, Stem Cell Program, Genomics Research Center, AS
2002-2005, Distinguished Research Fellow & Director of Institute of Zoology (IZ), AS, Taiwan
2002-, Adjunct Professor, Graduate Inst. of Clinical Medicine, National Taiwan Univ., Taiwan
1974-1977, Fellow in Biology, The Biological Laboratories, Harvard University, USA
1974,
Ph.D. Biophysics, University of Chicago, USA
1968, 1968, M.D., National Taiwan University, Taiwan

　

E-mail : johnyu@gate.sinica.edu.tw

Tel: 02-2789-9500

 

1. Stem Cell Biology:  

    The Stem Cell Program supported by the Genomics Research Center has been established as a dynamic multidisciplinary unit providing leadership at the forefront of stem cell research. This program provides an opportunity for researchers within ICOB to interact with GRC. The major focus consists of investigations into (1) cellular and genomic mechanisms of differentiation and plasticity, (2) reprogramming of stem cells from various sources, (3) derivation of primate/ human embryonic stem cells via novel technology development, and (4) somatic cell nucleus replacement. In striving for these goals, the Stem Cell Program recruits scientific expertise from abroad and facilitate platform technology transfer from academic institutes and/or biotech companies into Taiwan. Meanwhile, the Stem Cell Program also

promotes translational stem cell research to facilitate the transition of  lab

 bench studies to clinical trials and biotech development.

    A newly renovated research lab was opened, providing the up-to-date current facilities for research. We had established a core facility, which includes 8-fluorescence parameter FACSVantageDIVA, FACSCalibure, single cell assay/digital imaging, and confocal microscopy services. Currently, we hold weekly lab seminar with approximately 60 person attendance and offer a very popular graduate course on Stem Cell Biology for students from three major national universities in Taiwan.

　

2. Novel Experimental Animal Models for the Studies of Human Diseases and Drug Discovery

     We had developed a unique cell-based xenograft murine model of human primary leukemia for studying leukemia stem cells and prediction of clinical outcome. More recently, similar models have now been extended to include those solid tumors such as neuroblastoma, rhabdomyosarcoma, etc.

     In addition, zebrafish has become a powerful genetic model organism for studying vertebrate development and human diseases. We have built a modern core facility for chemical mutagenesis and mutant screening of zebrafish. Dr. C-C Huang is currently performing drug screening with the wild type and three existing angiogenesis mutants. Using the transgenic zebrafish TG(fli1:EGFP) that express green fluorescent protein in the vessel endothelial cells, three mutants, reg6, dac (dachshund), and prp (persistent plexus), had been isolated. We have also established the plateform technology of using zebrafish embroys for drug screening. We now screen for compounds in chemical library that disrupt vessel regeneration and/or correct the vessel phenotypes of our mutants. The long term goal of these projects is to identify genes that can be targets for drug development and new drugs that will help clinical treatment to patients with vessel diseases and/or cancers.

　

　

1. 幹細胞與再生醫學的研究

全新的幹細胞研究實驗室在92年五月底正式啟用，擁有最先進的研究設備，目前幹細胞團隊的精英包括： 游正博、李仲良、吳漢忠、郭紘志、沈家寧、陳淑華、邵立恩、林泰元等等。 

　

        幹細胞研究主要針對以下課題進行探討(1)幹細胞的細胞分化和基因變化以及他們調控的機制、(2)探討造血幹細胞和骨髓基質的相互作用、(3)靈長類/人類胚胎幹細胞株的建立與研究、(4)利用異體移殖動物模型來研發正常幹細胞分化及血癌幹細胞的研究、以及新治療法的創新。 

　

        為努力達成這些目標，幹細胞研究結合本土研究學者共同合作，同時促進他們更進一步的訓練。現在我們每星期舉辦研討會或討論會，邀請許多院內外學者一起參加，目前有將近60人參加，同時也替三所大學開設「幹細胞生物學」以培育研究生。此外，幹細胞研究團隊的一個重要任務即是積極引進國內外細胞療法之技術平台，銜接由實驗室、臨床試驗到生技研發間之需要。 

　

        幹細胞團隊還建立一套共同使用的研究設備，提供流式細胞儀及精密顯微影像分析的服務。流式細胞儀由全職且訓練有素的人員操作，目前己經建立八色螢光、多層次、高速細胞分離方法以成為各種幹細胞分離的技術平臺、也設置各種組織幹細胞之單一細胞篩選與培養技術、幹細胞培養之即時數位影像分析系統。

　

　

2. 人類疾病與藥物篩選的實驗動物模型 

我們建立一個特殊的人類腫瘤的異體移植的老鼠動物模式，除了人類血癌以外，我們也建造人類神經母細胞瘤，橫紋肌肉瘤等等腫瘤的動物模型，將進行人類腫瘤幹細胞和藥物篩選的實驗。   

　

        同時我們利用斑馬魚的遺傳及轉基因技術來研究血管再生的遺傳機制。黃政鎮已成功地篩選出3 株突變魚，其中reg6 影響血管分支造成類似人類hemangioma病症，dac 影響動脈改型，而prp則決定血管增生機制。我們也利用這些突變魚來建立藥物篩選的技術平台，目前已經有初步成功的案例，期望利用這些新穎的實驗動物模型能夠尋找新藥來治療人類血管疾病及控制腫瘤細胞組織的增生。

　

　

　

Selected Publications

  1. Yu, J. (2000) Involvement of activins and TGFs in hematopoiesis. in: Devel. Biol. of Hematopoiesis, Leonard I.   Zon (ed), Oxford Univ. Press, New York, pp 299-307.

  2. Dialynas, D.P., Lee, M.J., Gold, D.P., Shao, L.E., Yu, A.L., Borowitz, M.J., and Yu, J. (2001) Pre-conditioning with fetal cord blood facilitates engraftment of primary childhood T-ALL in immunodeficient mice. Blood 97: 3218-3225.

  3. Batova, A., Shao, L.E., Diccianni, M.B., Yu, A.L., Tanaka, T., Rephaeli, A., Nudelman, A., and Yu, J. (2002) The histone deacetylase inhibitor AN-9 has selective toxicity to drug-resistant primary leukemia and cancer cell lines. Blood 100: 3319- 3324.

  4. Diccianni, M.B., Gebauer, S., Meppelink, G., de Vries M., Yu, J., Shao, L., Shih, S., Carson, D.A., Yu, A.L. (2004) Small molecule CDK inhibitors suppress DNA synthesis and viability in T-ALL in a p16/pRb dependent fashion. J Exp Ther and Oncol 4: 223-237.

  5. Batova, A., Cottam, H., Yu, J., Diccianni, M.B., Carrera C.J. and Yu, A.L. (2005) 9-Beta-D-    erythrofuranosyladenine (EFA) is an effective salvage agent for methylthioadenosine phosphorylase-selective therapy  of T-cell acute lymphoblastic leukemia with L-alanosine. Blood (in press)