Professor Chen, Yun-Ru Ruby
Tel:02-27871275
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
- Deputy Director, Genomics Research Center, Academia Sinica, 2023-present
HONORS:
- Chung Hwa Rotary Education Foundation Outstanding Award, 2022-2023
- The 19th National Innovation Award. “A novel conformation-dependent monoclonal antibody against ALS and related neurodegenerative diseases”, 2022
- The 19th Y. Z. Hsu Scientific Paper Award, Far Eastern Y. Z. Hsu Science and Technology Memorial Foundation, 2021
- National China Youth Corps Youth Medal, Taiwan, 2019
- Selected work for Future Tech Exhibition “A novel potential therapeutic antibody to combat ALS and related neurodegenerative diseases”, 2018
- The 14th Young Investigator Award, TienTe Lee Biomedical Foundation, 2018
- Young Chemists Award of the Chemical Society, Taipei, 2016
- Ta-You Wu Memorial Award, 2015
- TWAS Young Affiliate, East & Southeast Asia and Pacific Region, 2015-2019
- The 13th Y.Z. Hsu Scientific Paper Award, 2015
- Academia Sinica Research Award for Junior Research Investigators, 2015
- Promising Women in Science Award, Wu Chieh Shiung Education Foundation, 2014
- Young Investigator Award, Biophysical Society of R.O.C., 2013
- Taiwan Dementia Society, LiFu Medical Research Foundation Academic Award, Advisor of the 1st Price, 2012, and 2nd Price, 2011
- The Taiwan Society for Biochemistry and Molecular Biology Traveling Fellowship, 2012
- Academia Sinica Postdoctoral Fellowship, 2006-2007
RESEARCH HIGHLIGHTS:
- 2014/11/14 Chinese Television News Magazine Interview
- 2014/09/16 TDP-43 protein aggregates are a key molecule causing dementia
- 2012/10/12 Negatively charged gold nanoparticles can correct the misfolding of key proteins associated with Alzheimer’s disease
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.
SELECTED PUBLICATIONS:
- Tien-Wei Lin, Jung-Kai Chang, Yih-Ru Wu, Tsung-Hsien Sun, Yang-Yu Cheng, Chien-Tai Ren, Mei-Hung Pan, Jin-Lin Wu, Kuo-Hsuan Chang, Hwai-I Yang, Chiung-Mei Chen*, Chung-Yi Wu*, and Yun-Ru Chen*, accepted, “Ganglioside-focused Glycan Array Reveals Abnormal Anti-GD1b Auto-antibody in Plasma of Preclinical Huntington’s Disease”, MOLECULAR NEUROBIOLOGY. (SCIE)
- Jin-Lin Wu and Yun-Ru Chen*, 2022, “Signal peptide stabilizes folding and inhibits misfolding of serum amyloid A”, PROTEIN SCIENCE, 31(12), e4485. (SCIE)
- Ming-Che Lee‡, Yi-Hung Liao‡, Shih-Hui Chen, and Yun-Ru Chen*., 2022, “Amyloid-β E22K Fibril in Familial Alzheimer’s Disease is More Thermo-stable and Susceptible to Seeding.”, IUBMB LIFE, 74(8), 739-747. (SCIE)
- Wan-Chin Chiang§, Yu-Sheng Fang§, Yuh-Shen Lye, Tzu-Yu Wong, Kiruthika Ganesan, Shih-Chieh Chou, Yun-Ru Chen*, 2022, “Hyperphosphorylation-mimetic TDP-43 Drives Amyloid Formation and Possesses Neuronal Toxicity at the Oligomeric Stage”, ACS Chemical Neuroscience, 37, 1,, 2599-2612. (SCIE)
- Jin-Lin Wu, Tung-Hung Su, Pei-Jer Chen, and Yun-Ru Chen*, 2022, “Acute‑phase serum amyloid A for early detection of hepatocellular carcinoma in cirrhotic patients with low AFP level”, Scientific Reports, 12, 5799. (SCIE)
- Yuh Shen Lye and Yun-Ru Chen*, 2022, “TAR DNA-binding protein 43 oligomers in physiology and pathology”, IUBMB LIFE, 2022, 1-18. (SCIE)
- Vu, Katrin; Lee, Ming-Che; Blankenburg, Gerhard; Chang, Yu-Jen; Chu, Ming-Lee; Erbe, Andreas; Lesser-Rojas, Leonardo; Chen, Yun-Ru; Chou, Chia-Fu*, 2021, “Time-evolved SERS signatures of DEP-trapped Aβ and Zn2+Aβ peptides revealed by a sub-10 nm electrode nanogap”, ANALYTICAL CHEMISTRY, 93(49), 16320-16329. (SCIE)
- Ya-Ling Chiang, Yu-Jen Chang, Yun-Ru Chen*, and Ing-Shouh Hwang*, 2021, “Effects of Dissolved Gases on Amyloid Fibril Morphology”, LANGMUIR, 37, 1,, 516-523. (SCIE)
- Yao-Hsiang Shih§, Ling-Hsien Tu§, Ting-Yu Chang, Kiruthika Ganesan, Wei-Wei Chang, Pao-Sheng Chang, Yu-Sheng Fang, Yeh-Tung Lin, Lee-Way Jin, and Yun-Ru Chen*, 2020, “TDP-43 interacts with amyloid-β, inhibits fibrillization, and worsens pathology in a model of Alzheimer’s disease”, NATURE COMMUNICATIONS, 11, 5950. (SCIE)
- Phillip Smethurst, Emmanuel Risse, Giulia E. Tyzack, Jamie S. Mitchell, Doaa M. Taha, Yun-Ru Chen, Jia Newcombe, John Collinge, Katie Sidle and Rickie Patani*, 2020, “Distinct responses of neurons and astrocytes to TDP-43 proteinopathy in amyotrophic lateral sclerosis”, BRAIN, 143(2), 430-440. (SCIE)
- Shih-Ling Huang, Lien-Szu Wu, Min Lee, Chin-Wen Chang, Wei-Cheng Cheng, Yu-Sheng Fang, Yun-Ru Chen, Pei-Lin Cheng, Che-Kun James Shen*, 2020, “A Robust TDP-43 Knock-In Mouse Model of ALS”, Acta Neuropathologica Communications, 8(1),3. (SCIE)
- Ling-Hsien Tu, Ning-Hsuan Tseng, Ya-Ru Tsai, Tien-Wei Lin, Yi-Wei Lo, Jien-Lin Charng, Hua-Ting Hsu, Yu-Sheng Chen, Rong-Jie Chen, Ying-Da Wu, Yi-Tsu Chan, Chang-Shi Chen, Jim-Min Fang,* and Yun-Ru Chen*, 2018, “Rationally Designed Divalent Caffeic Amide Inhibits Amyloid-β Fibrillization, Induce Fibril Dissociation, and Ameliorate Cytotoxicity”, EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, 158, 393-404. (SCIE)
- Chia-Jung Kuo, Hsu-Cheng Chiang, Chi-Ang Tseng, Chin-Fu Chang, Rajesh Kumar Ulaganathan, Tzu-Ting Ling, Yu-Jen Chang, Chiao-Chen Chen, Yun-Ru Chen, and Yit-Tsong Chen*., 2018, “A Lipid-Modified Graphene-Transistor Biosensor for Monitoring Amyloid-β Aggregation”, ACS APPLIED MATERIALS & INTERFACES, 10(15), 12311-12316. (SCIE)
- Ming-Che Lee, Wan-Cheng Yu, Yao-Hsiang Shih, Chun-Yu Chen, Zhong-Hong Guo, Shing-Jong Huang, Jerry C. C. Chan, and Yun-Ru Chen*, 2018, “Zinc ion rapidly induces toxic, off-pathway amyloid-β oligomers distinct from amyloid-β derived diffusible ligands in Alzheimer’s disease”, Scientific Reports, 8, 4772. (SCIE)
- Lin TW, Chang CF, Chang YJ, Liao YH, Yu HM, Chen YR*., 2017, “Alzheimer’s amyloid-β A2T variant and its N-terminal peptides inhibit amyloid-β fibrillization and rescue the induced cytotoxicity”, PLOS ONE, 12(3), e0174561. (SCIE)
- Nguyen Quoc Thai, Ning-Hsuan Tseng, Mui Thi Vu, Tin Trung Nguyen, Huynh Quang Linh, Chin-Kun Hu*, Yun-Ru Chen*, and Mai Suan Li*, 2016, “Discovery of DNA dyes Hoechst 34580 and 33342 as good candidates for Alzheimer’s disease: in silico and in vitro study”, JOURNAL OF COMPUTER-AIDED MOLECULAR DESIGN, 30(8), 639-50. (SCIE)
- Yu-Jen Chang, Nguyen Hoang Linh, Hui-Ming Yu, Mai Suan Li*, and Yun-Ru Chen*, 2016, “Alzheimer’s Amyloid-β Sequesters Caspase-3 in vitro via its C-terminal Tail.”, ACS Chemical Neuroscience, 7(8), 1097-1106. (SCIE)
- Yu-Jen Chang, U-Ser Jeng, Ya-Ling Chiang, Ing-Shouh Hwang, and Yun-Ru Chen*, 2016, “Glycine-Alanine Dipeptide Repeat from C9orf72 Hexanucleotide Expansions Forms Toxic Amyloids Possessing Cell-to-cell Transmission Property”, Journal of Biological Chemistry, 291(10), 4903-4911. (SCIE)
- Chia‑Wei Lee, Lan‑Ling Jang, Huei‑Jyuan Pan, Yun‑Ru Chen, Chih‑Cheng Chen, and Chau‑Hwang Lee*, 2016, “Membrane roughness as a sensitive parameter reflecting the status of neuronal cells in response to chemical and nanoparticle treatments”, Journal of Nanobiotechnology, 14, 9. (SCIE)
- Patricia F. Kao, Yun-Ru Chen, Xiao-Bo Liu, Charles DeCarli, William W. Seeley, and Lee-Way Jin*, 2015, “Detection of TDP-43 oligomers in frontotemporal lobar degeneration-TDP”, ANNALS OF NEUROLOGY, 78(2), 211-221. (SCIE)
- 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*, 2014, “Full-Length TDP-43 Forms Toxic Amyloid Oligomers that are Present in Frontotemporal Lobar Dementia-TDP Patients.”, Nature Communications, 5, 4824. (SCIE)
- 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. (SCIE)
- 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. (SCIE)
- 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. (SCIE)
- 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. (SCIE)
- 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. (SCIE)
- 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. (SCIE)
- 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. (SCIE)
- 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. (SCIE)
- 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. (SCIE)
- 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. (SCIE)
- 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. (SCIE)
- 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. (SCIE)
- 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. (SCIE)
- 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. (SCIE)
- Yun-Ru Chen and A. Clay Clark*, 2004, “Kinetic traps in the folding/unfolding of procaspase-1 CARD Domain”, Protein Science, 13, 2196-2206. (SCIE)
- 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. (SCIE)
- 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. (SCIE)