中央研究院 生物化學研究所

研究領域與專長

生物體內有上千萬個獨特的蛋白質分子在做工，促成了自然界多彩多姿的生命。蛋白質分子就好像螺絲起子、掃把、漏斗等日常生活用品一樣，不同的蛋白質分子以其特殊外型來發揮功用。因此，探索一個蛋白質分子的三度空間構造可以讓我們更加了解它在生物體內具有的功用，此蛋白質分子的結構資訊更可以被應用於設計與開發新型藥物。

我們實驗室專長於生產、純化、設計重組蛋白質，並致力於研究蛋白質結構與功能。實驗室主要研究技術包括蛋白質結晶、生化暨生物物理分析、電子顯微鏡單分子重建。運用上述現代結構生物學最新技術，我們研究負責清除細胞內蛋白質之機轉(包括自噬及巨噬作用等)的大型蛋白質降解機器以及設計能抑制這些生物巨分子功能的小分子藥物。

學經歷

• 1997 – 2002   博士, 生物物理, 美國德州大學達拉斯西南醫學中心
• 1990 – 1992   碩士, 生化暨分子生物研究所, 臺灣大學醫學院
• 1986 – 1990   學士, 藥學系, 臺灣大學醫學院

• 2023   傑出研究獎, 國科會
• 2022   深耕計畫獎助, 中研院
• 2020 – 迄今   合聘教授, 臺灣大學生命科學院生化科學研究所
• 2019 – 迄今   研究員, 中央研究院生物化學研究所
• 2019 – 2022   副所長, 中央研究院生物化學研究所
• 2017   教學優良獎, 臺灣大學
• 2010 – 2020   兼任副教授, 臺灣大學生命科學院生化科學研究所
• 2014 – 2019   長聘副研究員, 中央研究院生物化學研究所
• 2009 – 2014   副研究員, 中央研究院生物化學研究所
• 2006 – 2009   研究員, 輝瑞公司
• 2002 – 2006   博士後研究員, 美國霍華休斯醫學研究所

主要著作

Processive cleavage of substrate at individual proteolytic active sites of the Lon protease complex.    
Li S, Hsieh KY, Kuo CI, Su SC, Huang KF, Zhang K, Chang CI    
Science Advances (2021)

Complete three-dimensional structures of the Lon protease translocating a protein substrate.    
Li S, Hsieh KY, Kuo CI, Lee SH, Pintilie GD, Zhang K, Chang CI    
Science Advances (2021)

Molecular insights into substrate recognition and discrimination by the N-terminal domain of Lon AAA+ protease.    
Tzeng SR, Tseng YC, Lin CC, Hsu CY, Huang SJ, Kuo YT, Chang CI    
eLife (2021)

Structural Basis for the Differential Regulatory Roles of the PDZ Domain in C-Terminal Processing Proteases.    
Chueh CK, Som N, Ke LC, Ho MR, Reddy M, Chang CI    
mBio (2019)

Structural basis of adaptor-mediated protein degradation by the tail-specific PDZ-protease Prc.    
Su, M.-Y., Som, N., Wu, C-Y., Su, S.-C.,Kuo, Y.-T., Ke, L.-C., Ho, M.-R., Tzeng, S.-R., Teng, C.-H., Mengin-Lecreulx, D., Reddy, M., and Chang, C.-I    
Nature Communications (2017)

Structural Basis for the Magnesium-Dependent Activation and Hexamerization of the Lon AAA+ Protease.    
Su, S.-C., Lin, C.-C., Tai, H.-C., Ho, M.-R., Chang, M., Babu, S., Liao, J.-H., Wu, S.-H, Chang, Y.-C., Lim, C., and Chang, C.-I    
Structure (2016)

Structural Insights into the Allosteric Operation of the Lon AAA+ Protease.    
Lin, C.-C., Su, S.-C., Su, M.-Y., Liang, P.-H., Fang, C.-C., Wu, S.-H., and Chang, C.-I    
Structure (2016)

Structure of yeast Ape1 and its role in autophagic vesicle formation.    
Su MY, Peng WH, Ho MR, Su SC, Chang YC, Chen GC, Chang CI    
Autophagy (2015)

Structures of an ATP-independent Lon-like protease and its complexes with covalent inhibitors. (Cover article)    
J.-H. Liao, K. Ihara, C.-I. Kuo, K.-F. Huang, S. Wakatsuki, S.-H. Wu and C.-I. Chang    
Acta Crystallographica Section D Biological Crystallography (2013)

Structure of tracheal cytotoxin in complex with a heterodimeric pattern-recognition receptor.    
Chang CI, Chelliah Y, Borek D, Mengin-Lecreulx D, Deisenhofer J.    
Science (2006)

著作列表

1. Lee MS, Hsieh KY, Kuo CI, Lee SH, Garde S, Reddy M, (Chang CI)  (2022-02)  mBio  13(1), e03646-21  "Structural basis for the peptidoglycan editing activity of YfiH"
   
2. Li S, Hsieh KY, Kuo CI, Su SC, Huang KF, Zhang K, (Chang CI)  (2021-11)  Science Advances  7(46), eabj9537  "Processive cleavage of substrate at individual proteolytic active sites of the Lon protease complex."
   
3. Li S, Hsieh KY, Kuo CI, Lee SH, Pintilie GD, Zhang K, (Chang CI)  (2021-10)  Science Advances  7(42), eabj7835  "Complete three-dimensional structures of the Lon protease translocating a protein substrate."
   
4. Li S, Hsieh KY, Su SC, Pintilie GD, Zhang K, (Chang CI)  (2021-10)  Journal of Biological Chemistry  297(4), 101239  "Molecular basis for ATPase-powered substrate translocation by the Lon AAA+ protease."
   
5. Tzeng SR, Tseng YC, Lin CC, Hsu CY, Huang SJ, Kuo YT, (Chang CI)  (2021-04)  eLife  10, e64056  "Molecular insights into substrate recognition and discrimination by the N-terminal domain of Lon AAA+ protease."
   
6. Chueh CK, Som N, Ke LC, Ho MR, Reddy M, (Chang CI)  (2019-08)  mBio  10(4), e01129-19  "Structural basis for the differential regulatory roles of the PDZ domain in C-terminal processing proteases."
   
7. Su MY, Som N, Wu CY, Su SC, Kuo YT, Ke LC, Ho MR, Tzeng SR, Teng CH, Mengin-Lecreulx D, Reddy M, (Chang CI)  (2017-11)  Nature Communications  8, 1516  "Structural basis of adaptor-mediated protein degradation by the tail-specific PDZ-protease Prc."
   
8. Su SC, Lin CC, Tai HC, Chang MY, Ho MR, Babu CS, Liao JH, Wu SH, Chang YC, Lim C, (Chang CI)  (2016-05)  Structure  24(5), 676-686  "Structural basis for the magnesium-dependent activation and hexamerization of the Lon AAA+ protease."
   
9. Lin CC, Su SC, Su MY, Liang PH, Feng CC, Wu SH, (Chang CI)  (2016-05)  Structure  24(5), 667-675  "Structural insights into the allosteric operation of the Lon AAA+ protease."
   
10. Meyer PA, Socias S, Key J, Ransey E, Tjon EC, Buschiazzo A, Lei M, Botka C, Withrow J, Neau D, Rajashankar K, Anderson KS, Baxter RH, Blacklow SC, Boggon TJ, Bonvin AM, Borek D, Brett TJ, Caflisch A, (Chang CI), Chazin WJ, Corbett KD, Cosgrove MS, Crosson S, Dhe-Paganon S, Di Cera E, Drennan CL, Eck MJ, Eichman BF, Fan QR, Ferre-D'Amare AR, Fromme JC, Garcia KC, Gaudet R, Gong P, Harrison SC, Heldwein EE, Jia Z, Keenan RJ, Kruse AC, Kvansakul M, McLellan JS, Modis Y, Nam Y, Otwinowski Z, Pai EF, Pereira PJ, Petosa C, Raman CS, Rapoport TA, Roll-Mecak A, Rosen MK, Rudenko G, Schlessinger J, Schwartz TU, Shamoo Y, Sondermann H, Tao YJ, Tolia NH, Tsodikov OV, Westover KD, Wu H, Foster I, Fraser JS, Maia FR, Gonen T, Kirchhausen T, Diederichs K, Crosas M, Sliz P  (2016-03)  Nature Communications  7, 10882  "Data publication with the structural biology data grid supports live analysis."
    
11. Qi J, Singh S, Hua WK, Cai Q, Chao SW, Li L, Liu H, Ho Y, McDonald T, Lin A, Marcucci G, Bhatia R, Huang WJ, (Chang CI), Kuo YH  (2015-11)  Cell Stem Cell  17(5), 597-610  "HDAC8 Inhibition Specifically Targets Inv(16) Acute Myeloid Leukemic Stem Cells by Restoring p53 Acetylation."
    
12. Su MY, Peng WH, Ho MR, Su SC, Chang YC, Chen GC, (Chang CI)  (2015-09)  Autophagy  11(9), 1580-1593  "Structure of yeast Ape1 and its role in autophagic vesicle formation."
    
13. Chao SW, Su MY, Chiou LC, Chen LC, (Chang CI), Huang WJ  (2015-08)  Journal of Natural Products  78(8),1969-1976  "Total Synthesis of Hispidulin and the Structural Basis for Its Inhibition of Proto-oncogene Kinase Pim-1."
    
14. Lee SC, Lin CC, Wang CH, Wu PL, Huang HW, (Chang CI), Wu WG  (2014-07)  Journal of Biological Chemistry  289(29), 20170-20181  "Endocytotic Routes of Cobra Cardiotoxins Depend on the Spatial Distribution of Positively Charged and Hydrophobic Domains to Target Distinct Types of Sulfated Glycoconjugates on Cell Surface."
    
15. Su MY, (Chang CI), Chang CF  (2013-10)  Biomolecular NMR Assignments  7(2), 141-143  "(1)H, (13)C and (15)N resonance assignments of the pyrin domain from human PYNOD."
    
16. Li, J.-K., Liao, J.-H., Li, H., Kuo, C.-I, Huang, K.-F., Yang, L.-W., Wu, S.-H., and (Chang, C.-I)  (2013-09)  Acta Crystallographica Section D Biological Crystallography  D69(9), 1789-1797  "The N-terminal substrate-recognition domain of a LonC protease exhibits structural and functional similarity to cytosolic chaperones."
    
17. Liao, J.-H., Ihara, K., Kuo, C.-I, Huang, K.-F., Wakatsuki, S., Wu, S.-H., and (Chang, C.-I)  (2013-08)  Acta Crystallographica Section D Biological Crystallography  D69(8), 1395-1402  "Structures of an ATP-independent Lon-like protease and its complexes with covalent inhibitors"
    
18. Su, M.-Y., Kuo, C.-I, Chang, C.-F., and (Chang, C.-I)  (2013)  PLOS ONE  8(7), e67843  "Three-dimensional structure of human NLRP10/PYNOD pyrin domain reveals a homotypic interaction site distinct from its mouse homologue."
    
19. Wei-Jan Huang, Yi-ChingWang, Shi-Wei Chao, Chen-YuiYang, Liang-Chieh Chen, Mei-Hsiang Lin, Wen-Chi Hou, Mei-Yu Chen, Tai-Lin Lee, PingYang, and (Chung- I Chang)  (2012-10)  ChemMedChem  7(10), 1815-1824  "Synthesis and Biological Evaluation of ortho-Aryl N-Hydroxycinnamides as Potent Histone Deacetylase (HDAC) 8 Isoform-Selective Inhibitors"
    
20. Liao JH, Kuo CI, Huang YY, Lin YC, Lin YC, Yang CY, Wu WL, Chang WH, Liaw YC, Lin LH, (Chang CI), Wu SH  (2012)  PLOS ONE  7(7), e40226  "A Lon-Like Protease with No ATP-Powered Unfolding Activity."
    
21. Wei-Jan Huang, Ching-Chow Chen, Shi-Wei Chao, Chia-Chun Yu, Chen-Yui Yang, Jih-Hwa Guh, Yun-Chieh Lin, Chiao-I Kuo, Ping Yang and (Chung-I Chang)  (2011-09)  European Journal of Medicinal Chemistry  46(9), 4042-4049  "Synthesis and evaluation of aliphatic-chain hydroxamates capped with osthole derivatives as histone deacetylase inhibitors"
    
22. Huang WJ, Chen CC, Chao SW, Lee SS, Hsu FL, Lu YL, Hung MF, (Chang CI)  (2010-03)  ChemMedChem  5(4), 598-607  "Synthesis of N-Hydroxycinnamides Capped with a Naturally Occurring Moiety as Inhibitors of Histone Deacetylase."
    
23. Baxter RH, Chang CI, Chelliah Y, Blandin S, Levashina EA, Deisenhofer J.  (2007)  Proceedings of the National Academy of Sciences of the United States of America  104, 11615-11620  "Structural basis for conserved complement factor-like function in the antimalarial protein TEP1."
    
24. Chang CI, Deisenhofer J.  (2007)  Cell Mol Life Sci.  64, 1395-1402  "The peptidoglycan recognition proteins LCa and LCx."
    
25. Chang CI, Chelliah Y, Borek D, Mengin-Lecreulx D, Deisenhofer J.  (2006)  Science  311, 1761-1764  "Structure of tracheal cytotoxin in complex with a heterodimeric pattern-recognition receptor."
    
26. Chang CI, Ihara K, Chelliah Y, Mengin-Lecreulx D, Wakatsuki S, Deisenhofer J.  (2005)  Proceedings of the National Academy of Sciences of the United States of America  102, 10279-10284  "Structure of the ectodomain of Drosophila peptidoglycan-recognition protein LCa suggests a molecular mechanism for pattern recognition."
    
27. Chang CI, Pili-Floury S, Herve M, Parquet C, Chelliah Y, Lemaitre B, Mengin-Lecreulx D, Deisenhofer J.  (2004)  PLoS Biol.  2, 1293-1302  "A Drosophila pattern recognition receptor contains a peptidoglycan docking groove and unusual L,D-carboxypeptidase activity."
    
28. Goldsmith EJ, Cobb MH, Chang CI.  (2004)  Methods in Molecular Biology  250, 127-144  "Structure of MAPKs."
    
29. Goldsmith EJ, Chang CI.  (2002)  Structure  10, 888-889  "Another twist in helix C and a missing pocket."
    
30. Chang CI, Xu BE, Akella R, Cobb MH, Goldsmith EJ.  (2002)  Mol. Cell  9, 1241-1249  "Crystal structures of MAP kinase p38 complexed to the docking sites on its nuclear substrate MEF2A and activator MKK3b."