研究員

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EDUCATION AND POSITIONS HELD:

• B.S., Department of Agricultural Chemistry, National Taiwan University, Taiwan, 1992-1996
• Ph.D., Department of Molecular and Structural Biochemistry, North Carolina State University, USA, 1998-2003
• Research Assistant, Institute of Botany, Academia Sinica, 1996-1998
• Teaching Assistant, Dept. of Molecular and Structural Biochemistry, North Carolina State University, USA, 1998-1999
• Postdoctoral Fellow, Dept. of Molecular Biology & Biochemistry, University of California, Irvine, USA, 2004-2006
• Postdoctoral Fellow, Genomics Research Center, Academia Sinica, Taiwan, 2006-2007
• Assistant Professor, Genomics Research Center, Academia Sinica, Taiwan, 2007-2014
• Council Member of Asia Pacific Protein Association (APPA), 2014-2017
• The World Academy of Sciences (TWAS) Young Affiliate, 2015-2019
• Associate Professor, The Genomics Research Center, Academia Sinica, 2014-2021
• Adjunct Associate Professor, Dept. of Biochemical Science & Technology, National Taiwan University, Taiwan, 2015-present
• Professor, The Genomics Research Center, Academia Sinica, 2021-present
• Adjunct Professor, Dept. of Biochemical Science & Technology, National Taiwan University, Taiwan, 2021-present
• President-elect, Asia Pacific Protein Association (APPA), 2022-2025
• Adjunct Professor/ Adjunct Research Fellow, Biomedical Translation Research Center, Academia Sinica, Taiwan, 2022-present

HONORS:

• Chung Hwa Rotary Education Foundation Outstanding Award, 2022-2023
  2023 中華扶輪教育基金會2022-23年度「傑出/特殊人才」獎
• The 19^th National Innovation Award. “A novel conformation-dependent monoclonal antibody against ALS and related neurodegenerative diseases”, 2022
  2022 第19屆國家新創獎，「對抗漸凍人及相關神經退化疾病的結構專一型單株抗體」。
• The 19^th Y. Z. Hsu Scientific Paper Award, Far Eastern Y. Z. Hsu Science and Technology Memorial Foundation, 2021
  2021第十九屆有庠科技論文獎
• National China Youth Corps Youth Medal, Taiwan, 2019
  108年度救國團青年獎章
• Selected work for Future Tech Exhibition “A novel potential therapeutic antibody to combat ALS and related neurodegenerative diseases”, 2018
  技術團隊入選2018科技部未來科技展，作品”治療漸凍人及相關神經退化疾病的新穎抗體”
• The 14th Young Investigator Award, TienTe Lee Biomedical Foundation, 2018
  第14屆永信李天德青年醫藥科技獎
• Young Chemists Award of the Chemical Society, Taipei, 2016
  2016年中國化學會傑出青年化學家獎章
• Ta-You Wu Memorial Award, 2015
  104年度科技部吳大猷先生紀念獎
• TWAS Young Affiliate, East & Southeast Asia and Pacific Region, 2015-2019
  2015第三世界科學院年輕學者成員(國際獎項)
• The 13^th Y.Z. Hsu Scientific Paper Award, 2015
  第十三屆有庠科技論文獎
• Academia Sinica Research Award for Junior Research Investigators, 2015
  104年度中研院年輕學者著作學獎
• Junior Faculty Award, the 12th International Conference on Alzheimer’s Disease and Parkinson’s Disease, 2015(國際獎項)
• Promising Women in Science Award, Wu Chieh Shiung Education Foundation, 2014
  財團法人吳健雄學術基金會103年度台灣女科學家新秀獎
• Young Investigator Award, Biophysical Society of R.O.C., 2013 
  中華民國生物物理學會102年度傑出年輕學者獎
• Taiwan Dementia Society, LiFu Medical Research Foundation Academic Award, Advisor of the 1^st Price, 2012, and 2^nd Price, 2011
  台灣臨床失智症學會財團法人立夫醫藥文教基金會學術獎第一名之指導教授2012及第 二名之指導教授2011
• The Taiwan Society for Biochemistry and Molecular Biology Traveling Fellowship, 2012
  台灣生物化學及分子生物學會年輕學者出國研習優秀論文獎助2012 FAOBMB Congress
• Academia Sinica Postdoctoral Fellowship, 2006-2007

RESEARCH HIGHLIGHTS:

• 2014/11/14 華視新聞雜誌專訪
• 2014/09/16 TDP-43蛋白球狀多聚體是一導致失憶症的關鍵分子
• 2012/10/12 帶負電的奈米金粒子可導正阿茲海默症關鍵蛋白的錯誤摺疊

RESEARCH INTERESTS:

Protein Folding/Misfolding, Amyloids, and Neurodegenerative Diseases

My research focuses on understanding the mechanism of protein misfolding diseases, amyloidosis, by various techniques including biochemical, biophysical, molecular, and cellular methods. Our long-term goal is to elucidate the disease mechanisms of amyloidosis in the aspects of protein folding and structure, pathogenic protein interactions, and relate the results to the medical consequences. We further utilize the knowledge to develop novel diagnostic means and therapeutic modalities. Many ageing-related neurodegenerative diseases such as Alzheimer’s disease (AD) and Parkinson’s disease (PD) belong to amyloidosis. Among them, AD is the most serious problem in the 21st century. Amyloidosis is caused by aggregation of misfolded proteins to form amyloid fibrils comprising specific cross-β structures. Amyloid oligomers that exist in several neurodegenerative diseases imply a common toxicity mechanism in different neurodegenerative diseases. Currently, we are working on three amyloid and amyloid-like proteins and their interacting partners in neurodegenerative diseases. They are amyloid-β (Aβ) peptide and tau protein, the major substance in senile plaques and neurofibrillary tangles of AD patients respectively, α-synuclein, the component of Lewy bodies in PD, and TDP-43, a novel inclusion found in a subtype of frontotemporal lobar dementia (FTLD-U), amyotrophic lateral sclerosis (ALS), and AD. We start from elucidating the mechanism of such aggregation and further developing the diagnostic method, antibodies, and small molecule inhibitors. Moreover, we study the structure, function, and interactions of the related glycan conjugates, precursor proteins, and modifiers. The major research interests are listed as follows:

• Protein folding and misfolding of amyloids in neurodegenerative diseases.
• Amyloid protein oligomerization and the toxicity mechanisms in neurodegenerative diseases.
• Interactions of proteins, glycans, and lipids with the proteins involved in pathogenesis of the neurodegenerative diseases.
• Drug screening, diagnostic, and therapeutic developments in neurodegenerative diseases.

Amyloid formation, a detrimental protein aggregation, is initiated by protein  misfolding followed by self-association to ultimately form amyloid fibrils. The discovery of cytotoxic pre-fibrillar oligomers in many neurodegenerative  diseases underscores the importance of understanding the folding, aggregation, and pathogenic mechanisms as well as developing diagnostic and therapeutic methods.

 

蛋白質錯誤摺疊及類澱粉蛋白疾病致病機轉

我們的研究重點在於運用多種生物化學、生物物理、及分子細胞學的技術，來了解蛋白質錯誤摺疊之類澱粉沉積症的致病機轉。類澱粉沉積症多與神經退化疾病相關，其中阿茲海默症為本世紀全球及臺灣日趨嚴重的疾病。類澱粉蛋白是由錯誤摺疊的蛋白質堆積，而形成擁有專一乙級結構的纖維。類澱粉蛋白的堆積會形成許多不同的形狀物，而對神經細胞有毒害。很有趣的是，許多有著不同一級氨基酸序列的類澱粉蛋白，也有著共同的形狀物，這暗示著它們享有共同的堆積機制及相關毒性。我們將從了解致病蛋白堆積物的功能及機制，進而發展其偵測方式、有效抗體、及小分子抑制物。同時，我們亦研究類澱粉蛋白之醣化修飾及其調節物之影響與交互作用。我們希望能提供這些神經退化疾病早期診斷與治療的新方向。目前我們的研究著重於下列類澱粉蛋白及其作用分子:(1)阿茲海默症病人腦部老年斑塊的主要組成:類澱粉乙形蛋白(amyloid-β)及神經糾結之tau蛋白、(2)帕金森氏症病人腦部路易士體的主要組成α-synuclein、及(3)額顳葉失憶/肌萎縮側索硬化症中病癥的TDP-43蛋白。我們主要的研究目標如下:

• 蛋白質在神經退化疾病中的摺疊與錯誤摺疊機制
• 類澱粉蛋白多倍體及在神經退化疾病中引發之毒性機制
• 類澱粉蛋白之醣化修飾及其調節物之影響與交互作用
• 針對神經退化疾病發展藥物篩選、診斷及治療策略

 

SELECTED PUBLICATIONS: