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Chen, Yun-Ru Ruby 陳韻如

助研究員


Email: yrchen@gate.sinica.edu.tw
Telephone: 02-27871275



EDUCATION AND POSITIONS HELD:

  • B.S., Agricultural Chemistry, National Taiwan University, 1996
  • Ph.D., Molecular and Structural Biochemistry, North Carolina State University, 2003
  • Postdoctoral Researcher, Molecular Biology and Biochemistry, University of California at Irvine, 2004-2006
  • Postdoctoral Researcher, The Genomics Research Center, Academia Sinica, 2006-2007
  • Assistant Research Fellow, The Genomics Research Center, Academia Sinica, 2007-present

HONORS:

  • 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 1st Price, 2012, and 2nd 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 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 amyloidoses with 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 and therapeutic means. 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 worsening problem in the 21st century. Amyloidosis is caused by aggregation of misfolded proteins to form amyloid fibrils comprised of specific cross-β structures. Amyloid oligomers that existed 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 the neurodegenerative diseases. They are amyloid-β (Aβ) peptide, the major substance in senile plaques of the patient’s brain with AD, 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) and amyotrophic lateral sclerosis (ALS). We will start from elucidating the mechanism of such aggregation and further develop 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. For further details, please visit our lab homepage. 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 pathogenic proteins in the neurodegenerative disease mechanisms
  • Drug screening, diagnostic, and therapeutic developments in neurodegenerative diseases.
MissfoldingvsFolding
Amyloid formation, a detrimental protein aggregation, is initiated by
proteinmisfolding followed by self-association to ultimately form 
amyloid fibrils.The discovery of cytotoxic pre-fibrillar oligomers 
in many amyloidosis,especially neurodegenerative diseases, 
underscores the importance ofunderstanding the folding, aggregation,
and pathogenic mechanisms aswell 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,我們亦研究與類澱粉蛋白相關的醣分子、前驅物、及調節物之結構、功能、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及似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)、(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
  • 類澱粉蛋白多倍體化及在神經退化疾病中引發之毒性機制
  • 蛋白質、醣類、及脂質與病理相關蛋白在神經退化疾病中的其相互作用
  • 針對神經退化疾病發展藥物篩選、診斷及治療策略

 

SELECTED PUBLICATIONS:

  • Yu-Sheng Fang, Kuen-Jer Tsai, Yu-Jen Chang, Patricia Kao, Rima Woods, Pan-Hsien Kuo, Cheng-Chun Wu, Jhih-Ying Liao, Shih-Chieh Chou, Vinson Lin, Lee-Way Jin, Hanna S. Yuan, Irene H Cheng, Pang-Hsien Tu, and Yun-Ru Chen*, accepted, “Full-Length TDP-43 Forms Toxic Amyloid Oligomers that are Present in Frontotemporal Lobar Dementia-TDP Patients.”, Nature Communications. (SCI)
  • Huei-Jyuan Pan, Ruei-Lin Wang, Jian-Long Xiao, Yu-Jen Chang, Ji-Yen Cheng, Yun-Ru Chen, and Chau-Hwang Lee, 2014, “Using optical profilometry to characterize cell membrane roughness influenced by Amyloid-beta 42 aggregates and electric fields”, Journal of Biomedical Optics, 19(1), 011009. (SCI)
  • Yu-Jen Chang, Yun-Ru Chen*, 2014, “The Co-existence of an Equal Amount of Alzheimer’s Amyloid-β 40 and 42 forms Structurally Stable and Toxic Oligomers through a Distinct Pathway”, FEBS JOURNAL, 281(11), 2674-2687. (SCI)
  • Man Hoang Viet, Chun-Yu Chen, Chin-Kun Hu, Yun-Ru Chen*, and Mai Suan Li*., 2013, “Discovery of Dihydrochalcone as potential lead for Alzheimer's disease: in silico and in vitro study”, PLoS One, 8(11), e79151. (SCI)
  • Rong-Jie Chen, Wei-Wei Chang, Yu-Chun Lin, Pei-Lin Pheng, Yun-Ru Chen*, 2013, “Alzheimer’s Amyloid-β Oligomers Rescue Cellular Prion Protein Induced Tau Reduction via Fyn Pathways”, ACS Chemical Neuroscience, 4(9), 1287-1296. (SCI)
  • Yi-Ting Wang, Pan-Hsien Kuo, Chien-Hao Chiang, Jhe-Ruei Liang, Yun-Ru Chen, Shuying Wang, James C. K. Shen, and Hanna S. Yuan*., 2013, “The truncated C-terminal RRM domain of TDP-43 plays a key role in forming proteinaceous aggregates.”, J Biol. Chem., 288(13), 9049-9057. (SCI)
  • Winny Ariesandi, Chi-Fon Chang, Tseng-Erh Chen,Yun-Ru Chen*, 2013, “Temperature-dependent structural changes of Parkinson's alpha-synuclein reveal the role of pre-existing oligomers in alpha-synuclein fibrillization”, PLoS One, 8(1), e53487. (SCI)
  • Yi-Hung Liao, Yu-Jen Chang, Yuji Yoshiike, Yun-Chorng Chang*, and Yun-Ru Chen*, 2012, “Negatively charged gold nanoparticles inhibit Alzheimer's amyloid-beta fibrillization, induce fibril dissociation, and mitigate neurotoxicity”, SMALL, 8(23), 3631-3639. (SCI)
  • Wei-Ting Chen, Chen-Jee Hong, Ya-Tzu Lin, Wen-Han Chang, He-Ting Huang, Jhih-Ying Liao, Chih-Ya Cheng, Hsiu-Chih Liu, Yun-Ru Chen*, and Irene H Cheng *, 2012, “Amyloid-beta (Abeta) D7H mutation increases oligomeric Abeta42 and alters properties of Abeta-zinc/copper assemblies ”, PLos One, 7(4), e35807. (SCI)
  • Chun-Lun Ni, Hoi-Ping Shi, Kuo-Ging Lin, Hui-Ming Yu, and Yun-Ru Chen*, 2011, “Folding Stability of Amyloid-beta 40 Monomer is an Important Determinant of the Nucleation Phase in Fibrillization”, FASEB JOURNAL, 25(4),1390-1401. (SCI)
  • Wei-Ting Chen, Yi-Hung Liao, Hui-Ming Yu, Irene H. Cheng, and Yun-Ru Chen*, 2011, “Distinct Effects of Zn2+, Cu2+, Fe3+, and Al3+ on Amyloid-beta Stability, Oligomerization, and Aggregation: Amyloid-beta Destabilization Promotes Annular Protofibril Formation”, JOURNAL OF BIOLOGICAL CHEMISTRY, 286(11), 9646-9656. (SCI)
  • Ni-Shian Lin, John Ching-Hao Chao, Fang-Chieh Chou, Chi-Fon Chang, Yun-Ru Chen, Yu-Jen Chang, Shing-Jong Huang, Wei-Hsiang Tseng, and Jerry C. C. Chan, 2010, “Molecular Structure of Amyloid Fibrils Formed by Residues 127 to 147 of the Human Prion Protein”, Chemistry - A European Journal, 16(18), 5492-5499. (SCI)
  • Yuji Yoshiike, Ryoichi Minai, Yo Matsuo, Yun-Ru Chen, Tetsuya Kimura, Akihiko Takashima* , 2008, “Amyloid Oligomer Conformation in a Group of Natively Folded Proteins”, PLos ONE., 3(9), e3235. (SCI)
  • Yun-Ru Chen and Charles G. Glabe*, 2006, “Distinct Early Folding and Aggregation Properties of Alzheimer Amyloid-b Peptide Aβ40 and Aβ42: Stable Trimer or Tetramer Formation by Ab42”, J Biol. Chem, 281, 24414-24422. (SCI)
  • Yun-Ru Chen and A. Clay Clark*, 2006, “Substitutions of prolines examine their role in kinetic trap formation of the caspase recruitment domain (CARD) of RICK”, Protein Science, 15, 395-409. (SCI)
  • Yun-Ru Chen and A. Clay Clark*, 2004, “Kinetic traps in the folding/unfolding of procaspase-1 CARD Domain”, Protein Science, 13, 2196-2206. (SCI)
  • Yun-Ru Chen and A. Clay Clark*, 2003, “Equilibrium and Kinetic Folding of the α-Helical Greek Key Protein Domain: Caspase Recruitment Domain (CARD) of RICK”, Biochemistry, 42, 6310-6320. (SCI)
  • C. Pop, Y. R. Chen, B. Smith, K. Bose, B. Bobay, A. Tripathy, S. Franzen and A. C. Clark*, 2001, “Removal of the pro-domain does not affect the conformation of the procaspase-3 dimer”, Biochemistry, 40, 14224-14235. (SCI)