中央研究院 生物化學研究所

研究領域與專長

My research interest is regarding protein folding and misfolding behaviors in order to answer how proteins can fold into its native structure and how certain proteins can misfold and cause disease. Studies about protein folding are mainly the development of new methodologies to explore the folding process in order to unravel the intrinsic folding properties. Studies about protein misfolding are focus on two diseases: prion disease and Alzheimer’s disease. We are interested in studying the mechanism of amyloid fibril formation, factors influencing molecular assembly, designing inhibitor for amyloid formation, and species barrier in prion disease.

學經歷

• 1993 – 1998   博士, 生化系, 英國劍橋大學
• 1989 – 1991   碩士, 生化科學所, 國立臺灣大學
• 1985 – 1989   學士, 農業化學系, 國立臺灣大學

• 2017 – 迄今   研究員, 中央研究院生化所
• 2019 – 2022   副所長, 中央研究院生物化學研究所
• 2010 – 2017   副研究員, 中央研究院生化所
• 2003 – 2010   助研究員, 中央研究院生化所
• 1999 – 2003   博士後研究員, 中央研究院化學所
• 1992 – 1993   研究助理, 中央研究院生物化學所

主要著作

2.2 Å Cryo-EM Tetra-Protofilament Structure of the Hamster Prion 108–144 Fibril Reveals an Ordered Water Channel in the Center. 
Chen EH, Kao HW, Lee CH, Huang JYC, Wu KP*, Chen RP* 
Journal of the American Chemical Society (2022)

Biodistribution analysis of an intranasal-delivered peptide by the nanoSPECT/CT imaging. 
Lo WL, Wang YH, Chen EH, Wang SM, Chen LC, Chen RP* 
Journal of Drug Delivery Science and Technology (2022)

Location of the cross‐β structure in prion fibrils: A search by seeding and electron spin resonance spectroscopy. 
Chu BKY, Tsai RF, Hung CL, Kuo YH, Chen EH., Chiang YW*, Chan SI*, Chen RP* 
Protein Science (2022)

A Systematic Study of the Stability, Safety, and Efficacy of the de novo Designed Antimicrobial Peptide PepD2 and Its Modified Derivatives Against Acinetobacter baumannii. 
Chen SP, Chen EH, Yang SY, Kuo PS, Jan HM, Yang TC, Hsieh MY, Lee KT, Lin CH , Chen RP* 
Frontiers in Microbiology (2021)

An intranasally delivered peptide drug ameliorates cognitive decline in Alzheimer transgenic mice.  
Cheng YS, Chen ZT, Liao TY, Lin C, Shen HC, Wang YH, Chang CW, Liu RS, Chen RP, Tu PH  
EMBO molecular medicine (2017)

Revealing structural changes of prion protein during conversion from alpha-helical monomer to beta-oligomers by means of ESR and nanochannel encapsulation.  
Yang, C., Lo, W. L., Kuo, Y. H., Sang, J. C., Lee, C. Y., Chiang, Y. W. & Chen, R. P.  
ACS Chem Biol (2015)

Slow spontaneous α-to-β structural conversion in a non-denaturing neutral condition reveals the intrinsically disordered property of the disulfide-reduced recombinant mouse prion protein.  
Sang, J. C., Lee, C. Y., Luh, F. Y., Huang, Y. W., Chiang, Y. W. & Chen, R. P.  
Prion (2012)

A new amyloid-like beta-aggregate with amyloid characteristics, except fibril morphology.  
Chang ES, Liao TY, Lim TS, Fann W, Chen RP  
JOURNAL OF MOLECULAR BIOLOGY (2009)

Quantifying the Sequence-Dependent Species Barrier between Hamster and Mouse Prions.  
Lee, L.Y., and Chen, R.P.  
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY (2007)

Measuring the refolding of beta-sheets with different turn sequences on a nanosecond time scale.  
Chen, R.P., Huang, J.J., Chen, H.L., Jan, H., Velusamy, M., Lee, C.T., Fann, W.S., Larsen, R.W., and Chan, S.I.  
Proc. Natl. Acad. Sci. USA (2004)

著作列表

1. Chu BK, Lin YS, Shen HC, (Chen RP)*  (2023)  Methods in Molecular Biology  2551, 633-647  "Cross-Seeding Assay in the Investigation of the Amyloid Core of Prion Fibrils."
   
2. Chen EH, Kao HW, Lee CH, Huang JYC, Wu KP*, (Chen RP)*  (2022-08)  Journal of the American Chemical Society  144(30), 13888-13894  "2.2 Å Cryo-EM Tetra-Protofilament Structure of the Hamster Prion 108-144 Fibril Reveals an Ordered Water Channel in the Center."
   
3. Chen EH, Lin KM, Sang JC, Ho MR, Lee CH, Shih O, Su CJ, Yeh YQ, Jeng US, (Chen RP)*  (2022-08)  IUBMB life  74(8), 780-793  "Condition-dependent structural collapse in the intrinsically disordered N-terminal domain of prion protein."
   
4. Lo WL, Wang YH, Chen EH, Wang SM, Chen LC, (Chen RP)*  (2022-07)  Journal of Drug Delivery Science and Technology  73, 103454  "Biodistribution analysis of an intranasal-delivered peptide by the nanoSPECT/CT imaging"
   
5. Chu BKY, Tsai RF, Hung CL, Kuo YH, Chen EH., Chiang YW*, Chan SI*, (Chen RP)*  (2022-06)  Protein Science  31(6), e4326  "Location of the cross‐β structure in prion fibrils: A search by seeding and electron spin resonance spectroscopy"
   
6. Chen EH, Weng CW, Li YM, Wu MC, Yang CC, Lee KT, (Chen RP)*, Cheng CP*  (2021-09)  Frontiers in Plant Science  12, 753217  "De Novo Design of Antimicrobial Peptides With a Special Charge Pattern and Their Application in Combating Plant Pathogens."
   
7. Matiadis D, Ng ST, Chen EH, Nigianni G, Vidali VP, Canko A, (Chen RP)*, Sagnou M*  (2021-08)  Biomedicines  9(8), 955  "Synthesis and Biological Evaluation of Hydroxylated Monocarbonyl Curcumin Derivatives as Potential Inducers of Neprilysin Activity"
   
8. Chen SP, Chen EH, Yang SY, Kuo PS, Jan HM, Yang TC, Hsieh MY, Lee KT, Lin CH , (Chen RP)*  (2021-06)  Frontiers in Microbiology  12, 678330  "A Systematic Study of the Stability, Safety, and Efficacy of the de novo Designed Antimicrobial Peptide PepD2 and Its Modified Derivatives Against Acinetobacter baumannii"
   
9. Lin YC, Chen EH, (Chen RP), Dunny GM, Hu WS, Lee KT  (2021-06)  Applied and environmental microbiology  87(13), e0044221  "Probiotic Bacillus Affect Enterococcus faecalis Antibiotic Resistance Transfer by Interfering with Pheromone Signaling Cascades."
   
10. Sneideris T, Ziaunys M, Chu BY, (Chen RP), Smirnovas V  (2020-10)  Int. J. Mol. Sci.  21(19), E7410  "Self-Replication of Prion Protein Fragment 89-230 Amyloid Fibrils Accelerated by Prion Protein Fragment 107-143 Aggregates."
    
11. Shen HC, Chen YH, Lin YS, Chu BK, Liang CS, Yang CC, (Chen RP)  (2019-06)  Neurochemical research  44(6),1399-1409  "Segments in the Amyloid Core that Distinguish Hamster from Mouse Prion Fibrils."
    
12. Chen ZT, Hung MJ, Yu SJ, Liao TY, Lin YP, (Chen RP), Yang CC, Charng YY  (2019-02)  bioRxiv  553503  "Divergence in Thermostability of Arabidopsis Mitochondrial Nucleotide Exchange Factors Encoded by Duplicate Genes, MGE1 and MGE2."
    
13. Chen EH, Lu TT, Hsu JC, Tseng YJ, Lim TS, (Chen RP)  (2017-08)  Scientific reports  7(1), 8691  "Directly monitor protein rearrangement on a nanosecond-to-millisecond time-scale."
    
14. Cheng YS, Chen ZT, Liao TY, Lin C, Shen HC, Wang YH, Chang CW, Liu RS, (Chen RP), Tu PH  (2017-05)  EMBO molecular medicine  9(5), 703-715  "An intranasally delivered peptide drug ameliorates cognitive decline in Alzheimer transgenic mice."
    
15. Wang BJ, Her GM, Hu MK, Chen YW, Tung YT, Wu PY, Hsu WM, Lee H, Jin LW, Hwang SL, (Chen RP), Huang CJ, Liao YF  (2017-04)  Proceedings of the National Academy of Sciences of the United States of America  114(15), E3129-E3138  "ErbB2 regulates autophagic flux to modulate the proteostasis of APP-CTFs in Alzheimer's disease."
    
16. (Chen RP)  (2017-03)  Journal of Alzheimers Disease & Parkinsonism  7(2), 314  "From nose to brain: The promise of peptide therapy for alzheimer’s disease and other neurodegenerative diseases."
    
17. How SC, Yang SM, Hsin A, Tseng CP, Hsueh SS, Lin MS, (Chen RP), Chou WL, Wang SS  (2016-12)  Food & function  7(12), 4898-4907  "Examining the inhibitory potency of food additive fast green FCF against amyloid fibrillogenesis under acidic conditions."
    
18. Saito M, Kamonprasertsuk S, Suzuki S, Nanatani K, Oikawa H, Kushiro K, Takai M, Chen PT, Chen EH, (Chen RP), Takahashi S  (2016-09)  JOURNAL OF PHYSICAL CHEMISTRY B  120(34), 8818-8829  "Significant Heterogeneity and Slow Dynamics of the Unfolded Ubiquitin Detected by the Line Confocal Method of Single-Molecule Fluorescence Spectroscopy."
    
19. Wu BK, Yuan RY, Chang YP, Lien HW, Chen TS, Chien HC, Tong TS, Tsai HP, Fang CL, Liao YF, Chang CC, (Chen RP), Huang CJ  (2016-08)  Biochemical and biophysical research communications  477(2), 283-289  "Epicatechin isolated from Tripterygium wilfordii extract reduces tau-GFP-induced neurotoxicity in zebrafish embryo through the activation of Nrf2."
    
20. Chen PT, Chen ZT, Hou WC, Yu LC, (Chen RP)  (2016-07)  Scientific Reports  6, 29760  "Polyhydroxycurcuminoids but not curcumin upregulate neprilysin and can be applied to the prevention of Alzheimer's disease"
    
21. Lin CY, Cheng YS, Liao TY, Lin C, Chen ZT, Twu WI, Chang CW, Tan DT, Liu RS, Tu PH, (Chen RP)  (2016-06)  Journal of Alzheimer's disease  53(3), 1053-1067  "Intranasal Administration of a Polyethylenimine-Conjugated Scavenger Peptide Reduces Amyloid-beta Accumulation in a Mouse Model of Alzheimer's Disease."
    
22. Chen PT, Chen CL, Lin LT, Lo CH, Hu CJ, (Chen RP), Wang SS  (2016-04)  PloS one  11(4), e0153360  "Design of Peptide Substrate for Sensitively and Specifically Detecting Two Abeta-Degrading Enzymes: Neprilysin and Angiotensin-Converting Enzyme."
    
23. Hsieh YL, Lu CF, Chiang BY, Liao SC, (Chen RP), Lin CS, Wang AY, Yang CC  (2016-04)  Plant Molecular Biology Reporter  34(2), 387-398  "Molecular characterization of ethylene response sensor 1 (BoERS1) in Bambusa oldhamii."
    
24. Wu BK, Yuan RY, Lien HW, Hung CC, Hwang PP, (Chen RP), Chang CC, Liao YF, Huang CJ  (2016-02)  Journal of biomedical science  23(1), 25  "Multiple signaling factors and drugs alleviate neuronal death induced by expression of human and zebrafish tau proteins in vivo."
    
25. Yang C, Lo WL, Kuo YH, Sang JC, Lee CY, Chiang YW, (Chen RP)  (2015-02)  ACS chemical biology  10(2), 493-501  "Revealing structural changes of prion protein during conversion from alpha-helical monomer to beta-oligomers by means of ESR and nanochannel encapsulation"
    
26. Chen Lin, Eric H.-L. Chen, Lily Y.-L. Lee, Ruei-Lin Hsu, Frederick Y. Luh, Li-ling Yang, Chia-Fu Chou, Li-De Huang, Chun-Cheng Lin, (Rita P.-Y. Chen)  (2014-03)  Carbohydrate Research  387, 46-53  "Comparison of the anti-amyloidogenic effect of O-mannosylation, O-galactosylation, and O-GalNAc glycosylation"
    
27. Chuang CC, Liao TY, Chen EH, (Chen RP)*  (2013-10)  Amino acids  45(4), 785-796  "How do amino acid substitutions affect the amyloidogenic properties and seeding efficiency of prion peptides."
    
28. Chatterjee B, Lee CY, Lin C, Chen EH, Huang CL, Yang CC, (Chen RP)*  (2013-07)  PloS one  8(7), e67967  "Amyloid core formed of full-length recombinant mouse prion protein involves sequence 127-143 but not sequence 107-126."
    
29. Hsu JC, Chen HL, Snoeberger RC, Luh FY, Lim TS, Hsu C, (Chen RP)*  (2013-04)  Journal of physical chemistry B  117(13), 3459-3468  "Thioflavin T and Its Photoirradiative Derivatives: Exploring Their Spectroscopic Properties in the Absence and Presence of Amyloid Fibrils"
    
30. Liu KN, Lai CM, Lee YT, Wang SN, (Chen RP), Jan JS, Liu HS, Wang SS*  (2012-11)  BIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS  1820(11), 1774-1786  "Curcumin's pre-incubation temperature affects its inhibitory potency toward amyloid fibrillation and fibril-induced cytotoxicity of lysozyme."
    
31. Sang JC, Lee CY, Luh FY, Huang YW, Chiang YW, (Chen RP)*  (2012-11)  Prion  6(5), 489-497  "Slow spontaneous alpha-to-beta structural conversion in a non-denaturing neutral condition reveals the intrinsically disordered property of the disulfide-reduced recombinant mouse prion protein."
    
32. Kao AL, Lin YH, (Chen RP), Huang YY, Chen CC, Yang CC*  (2012-06)  Phytochemistry  78, 7-19  "E3-independent ubiquitination of AtMAPR/MSBP1."
    
33. Yang, L. L., Kao, M. W., Chen, H. L., Lim, T. S., Fann, W. & (Chen, R. P.)*   (2012-02)  European Biophysics Journal with Biophysics Letters  41(2), 189-198  "Observation of protein folding/unfolding dynamics of ubiquitin trapped in agarose gel by single-molecule FRET"
    
34. Liao TY, Lee LY, (Chen RP)*  (2011-11)  FEBS journal  278(22), 4351-4361  "Leu138 in the bovine prion peptide fibrils is involved in the seeding discrimination related to codon-129 M/V polymorphism in the prion peptide seeding experiment."
    
35. Chen HL, Hsu JC, Viet MH, Li MS, Hu CK, Liu CH, Luh FY, Chen SS, Chang ES, Wang AH, Hsu MF, Fann W, (Chen RP)*  (2010-11)  Proteins  78(14), 2973-2983  "Studying submicrosecond protein folding kinetics using a photolabile caging strategy and time-resolved photoacoustic calorimetry."
    
36. Chen PT, Liao TY, Hu CJ, Wu ST, Wang SS, (Chen RP)*  (2010-06)  Journal of neuroscience methods  190(1), 57-62  "A highly sensitive peptide substrate for detecting two Abeta-degrading enzymes: Neprilysin and insulin-degrading enzyme."
    
37. Huang, T.Y., Cook, C.E., Davis, G. K., Shigenobu, S., (Chen, R.P.) and Chang, C.C.*   (2010-03)  INSECT MOLECULAR BIOLOGY  19(2), 75-85  "Anterior development in the parthenogenetic and viviparous form of the pea aphid, Acyrthosiphon pisum: hunchback and orthodenticle expression."
    
38. Chen, A.K., Lin, R.Y., Xie, E.Z., Tu, P.H., (Chen, R.P.) and Liao, T.Y., Chen, W., Wang, C.H. and Huang, J.H.*  (2010-02)  JOURNAL OF THE AMERICAN CHEMICAL SOCIETY  132(4), 1186-1187  "Induction of amyloid fibrils by the C-terminal fragments of TDP-43 in amyotrophic lateral sclerosis."
    
39. Tsai WB*, (Chen RP), Wei KL, Tan SF, Lai JY  (2010)  JOURNAL OF BIOMATERIALS SCIENCE-POLYMER EDITION  21(3), 377-394  "Modulation of RGD-functionalized polyelectrolyte multilayer membrane for promoting osteoblast function. "
    
40. Lee MM, Isaza CE, White JD, (Chen RP), Liang GF, He HT, Chan SI, Chan MK*  (2009-11)  PROTEINS-STRUCTURE FUNCTION AND BIOINFORMATICS  77(3), 647-657  "Insight into the substrate length restriction of M32 carboxypeptidases: Characterization of two distinct subfamilies."
    
41. Tsai WB*, (Chen RP), Wei KL, Chen YR, Liao TY, Liu HL, Lai JY  (2009-11)  ACTA BIOMATERIALIA  5(9), 3467-3477  "Polyelectrolyte multilayer films functionalized with peptides for promoting osteoblast functions."
    
42. Ho CC, Lee LY, Huang KT, Lin CC, Ku MY, Yang CC, Chan SI, Hsu RL, (Chen RP)*  (2009-07)  PROTEINS-STRUCTURE FUNCTION AND BIOINFORMATICS  76(1), 213-225  "Tuning the conformational properties of the prion peptide."
    
43. Chang ES, Liao TY, Lim TS, Fann W, (Chen RP)*  (2009-01)  JOURNAL OF MOLECULAR BIOLOGY  385(4), 1257-1265  "A new amyloid-like beta-aggregate with amyloid characteristics, except fibril morphology."
    
44. Hsu RL, Lee KT, Wang JH, Lee LY, (Chen RP)*  (2009-01)  JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY  57(2), 503-508  "Amyloid-degrading ability of nattokinase from Bacillus subtilis natto."
    
45. Chang, C.C.*, Huang, T.Y., Cook, C.E., Lin, G.W., Shih, C.L., and (Chen, R.P. )   (2009-01)  INTERNATIONAL JOURNAL OF DEVELOPMENTAL BIOLOGY  53(1), 169-176  "Developmental expression of Apnanos during oogenesis and embryogenesis in the parthenogenetic pea aphid Acyrthosiphon pisum"
    
46. Isaza, C.E., Zhong, X., Rosas, L.E., White, J.D., (Chen, R.P.), Liang, G.F., Chan, S.I., Satoskar, A.R., and Chan, M.K.*  (2008-08)  BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS  373(1), 25-29  "A proposed role for Leishmania major carboxypeptidase in peptide catabolism"
    
47. (Chen, R.P.), Liang, F.C., Lee, C.T., Zerella, R., and Chan, S.I.*  (2008-08)  JOURNAL OF THE CHINESE CHEMICAL SOCIETY  55(4), 772-781  "Contributions of a surface hydrophobic cluster to the folding and structural stability of ubiquitin"
    
48. Kao, M.W., Yang, L.L., Lin, J.C., Lim, T.S., Fann, W.*, and (Chen, R.P.)*  (2008-06)  BIOCONJUGATE CHEMISTRY  19(6), 1124-1126  "Strategy for efficient site-specific FRET-dye labeling of ubiquitin"
    
49. Lee, L.Y., and (Chen, R.P.)*  (2007-02)  JOURNAL OF THE AMERICAN CHEMICAL SOCIETY  129, 1644-1652  "Quantifying the Sequence-Dependent Species Barrier between Hamster and Mouse Prions"
    
50. Liang, F.C., (Chen, R.P.), Lin, C.C., Huang, K.T., and Chan, S.I.*  (2006-04)  BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS  342(2), 482-488  "Tuning the conformation properties of a peptide by glycosylation and phosphorylation"
    
51. N. N. Huo, J. J. Huang, J. Miksovska, R. P.Chen, R. W. Larsen and S. I. Chan*  (2005-12)  JOURNAL OF THE AMERICAN CHEMICAL SOCIETY  127, 16945-16954  "Effects of turn stability on the kinetics of refolding of a hairpin in a beta-sheet"
    
52. (Chen, R.P.), Huang, J.J., Chen, H.L., Jan, H., Velusamy, M., Lee, C.T., Fann, W.S., Larsen, R.W., and Chan, S.I.*  (2004-05)  PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA  101, 7305-7310  "Measuring the refolding of beta-sheets with different turn sequences on a nanosecond time scale"
    
53. R. P. Chen*  (2004)  J Gen Mol Biol  15, 88-95  "The history and new progress of prion diseases"
    
54. (Chen, P.Y.), Lin, C.C., Chang, Y.T., Lin, S.C., and Chan, S.I.*  (2002-10)  PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA  99(20), 12633-12638  "One O-linked sugar can affect the coil-to-beta structural transition of the prion peptide"
    
55. P. Y. Chen, C. K. Lin, C. T. Lee, H. Jan and S. I. Chan*  (2001)  Protein Sci  10, 1794-1800  "Effects of turn residues in directing the formation of the beta-sheet and in the stability of the beta-sheet"
    
56. P. Y. Chen, B. G. Gopalacushina, C. C. Yang, S. I. Chan* and P. A. Evans  (2001)  Protein Sci  10, 2063-2074  "The role of a beta-bulge in the folding of the beta-hairpin structure in ubiquitin"
    
57. R. Zerella, P. Y. Chen, P. A. Evans, A. Raine and D. H. Williams*  (2000)  Protein Sci  9, 2142-2150  "Structural characterization of a mutant peptide derived from ubiquitin: implications for protein folding"