副研究員
02-2787-1247
EDUCATION AND POSITIONS HELD:
- Associate Professor, Stem Cell Program, Genomics Research Center, Academia Sinica, Taiwan. 2015-present
- Assistant Professor, Stem Cell Program, Genomics Research Center, Academia Sinica, Taiwan. 2007-2015
- Adjunct Assistant Professor, Genomics and System Biology Program, College of Life Science, National Taiwan University, Taiwan. 2010-present
- Co-PI, National RNAicore Facility Plateform, 2009-present
- Postdoctoral Fellow/Associate, Molecular, Department of Cellular, and Developmental Biology, Yale University, USA. 2003-2007
- Postdoctoral Fellow, Graduate Institute of Microbiology, College of Medicine, National Taiwan University, Taiwan. 2001-2003
- Ph.D. Institute of Microbiology, National Taiwan University, Taipei, Taiwan. 1995-2000
- M.S. Institute of Molecular Medicine, National Taiwan University, Taipei, Taiwan. 1992-1994
- B.S. Department of Medical Technology, National Taiwan University, Taipei, Taiwan. 1988-1992
- Research Assistant, Graduate Institute of Microbiology, College of Medicine, National Taiwan University, Taiwan. 1994-1995
HONORS:
- Ruth L. Kirschstein National Research Service Award, 2003-2004, NIH
- Outstanding Paper Award, National Taiwan University, 2002
RESEARCH INTERESTS:
High throughput functional screens pinpoints key factors for cell fate determination
Research Figure/Table/Scheme
Stem cell renewal and differentiation is important for stem cell biology and regenerative medicine. To efficiently pinpoint factors critical for cell fate determination, systematically functional screens were performed in mouse embryonic stem cells (ESCs), human ESCs, and mesenchymal stem cells (MSCs). We established the first shRNA screen in ESCs. With a shRNA library of kinases and phosphatases contains 4796 shRNAs, we identified 244 genes essential for ESC renewal. Among them, Nme6 and Nme7 is essential for 8 stemness genes expressions. With 517 shRNAs target genes are differentially expressed in undifferentiated human ESCs and differentiated cells or are embryonic lethal, we performed a shRNA functional screen and found 86 genes essential for human ESC renewal. And two candidate genes either bridge the oxidation and reduction status of ESCs with stemness signals, or block neural stem cell differentiation are currently studied in-depth. To fulfill the unmet need of bone diseases, a gain-of-function screen was performed with an overexpression library contains 12380 genes. 9 candidate genes are found to be essential and sufficient to promote the osteogenesis of human MSCs. By this method, we found soluble factor that can completely treat and prevent osteoporosis. Thus we found many factors play critical roles for ESC and MSC renewal and differentiation by systematically functional screens.
對幹細胞生物學和再生醫學來說，幹細胞的自我更新與分化是很重要的。為了有效地找尋決定細胞的命運的樞紐因子，我們在小鼠胚胎幹細胞，人類胚胎幹細胞，和間質幹細胞進行系統性功能篩選。我們建立了第一個在胚胎幹細胞的shRNA篩選。我們以4796個shRNA進行激酶和磷酸酶的功能性篩選，並發現了244個基因對胚胎幹細胞的自我更新是必要的。其中，Nme6和Nme7對8個幹細胞特性基因的表達是必需的。我們另以在未分化的胚胎幹細胞和分化細胞差異表現基因或對胚胎致死基因所設計的517個 shRNA，在人類胚胎幹細胞進行功能性篩選。我們發現有86個基因對人類胚胎幹細胞的自我更新是必要的。目前針對其中有兩個候選基因正在進行進一步的研究。這兩個候選基因可連結胚胎幹細胞特性訊息與細胞氧化還原狀態，或阻止神經幹細胞的分化。為了解決骨骼疾病中待解決的問題，在我們在間質幹細胞過度表達12380個基因。至少有9個候選基因被發現對成骨作用是必要的，且過度表達這些基因足以促進間質幹細胞的成骨作用。藉由這個方法，我們發現可溶性因子可以完全地治療與預防骨質疏鬆症。因此，透過系統性功能篩選，我們發現許多樞紐因子在胚胎幹細胞和間質幹細胞的自我更新與分化扮演關鍵性的角色。