特聘研究員 / 本院細生所

EDUCATION AND POSITIONS HELD:

• M.D., National Taiwan University, 1968
• Ph.D. Biophysics, University of Chicago, 1974
• Fellow in Biology, The Biological Laboratories, Harvard University, 1974–1977
• Director, Experimental Hematalogy, The Scripps Research Institute, 1998–2002
• Distinguished Research Fellow and Director of Institute of Zoology, Academia Sinica
• Adjunct Professor, Graduate Institute of Clinical Medicine, National Taiwan University

HONORS:

• Board of Directors, National Applied Research Laboratories, Taiwan, 2003–present
• Advisory Board: NTHU/ITRI Joint Research Center; National Science & Technology Program in Biotech/Drug Research & Development; National Experimental Animal Center, 2003–present
• Advisory Board: Science & Technology Law Center, Institute for Information Industry, 2004–present.
• ROC committee, International Union of Biological Sciences, 2004–present.
• Chief Editor, Zoological Studies
• Editorial Board, J. Formosan. Med. Assoc.
• US NIH Special Grants Review Committee NIDDK, 1995–2000
• Review Committee for Small Business Innovation Research, 1997–1999
• Committee for Center of Excellence in Molecular Hemataolgy,1993Cell Biology & Physiology Study Section, 1989
• Established Investigatorship Award, Americna Heart Association, 1978–1983

RESEARCH INTERESTS:

Stem Cell Biology/Regenerative Medicine

1. Stem Cell Biology:

The Stem Cell Program has been established as a dynamic multidisciplinary unit providing leadership at the forefront of stem cell research. 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. 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, we have built a modern core facility for chemical mutagenesis and mutant screening of zebrafish. We are using zebrafish for drug discovery and prediction of biological function for novel genes. Using the transgenic zebrafish TG(fli1:EGFP) that express green fluorescent protein, we had isolated mutants and established the plateform technology of using zebrafish embroys for drug screening. The long term goal of these projects is to identify genes that can be targets for drug developmen.

Furthermore, using computational and evolutionary genomics, Dr. Li Wen-Hsiung at GRC had identified 13,711 KaKs-predicted exons which are present in both mouse and human genome. However, the existence of the transcript remains to be validated and biological functions have yet to be explored. We are using zebrafish to identify and characterize the biological functions of these new genes based on a novel zebrafish platform technology of assays. So far, we have identified several new genes expressed in specific tissues as well as in human malignancies.

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，目前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。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。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、藥物篩選、與研發基因功能的實驗動物模型
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，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，建立藥物篩選的技術平台。我們也利用斑馬魚尋找新基因的生物功能特異組織及腫瘤細胞表現。目前已經有初步成功的案例。期望研發新藥來治療人類疾病及控制腫瘤的增生。