Research

Intracellular protein degradation serves multiple vital functions in all living cells. For example, selective degradation of regulatory proteins such as transcription factors and cell cycle regulators allows rapid change in their concentration within the cell, which represents an effective form of regulation. Another important function of intracellular proteolysis is to rid the cell of potentially harmful proteins that are misfolded or damaged, which may be altered due to abnormal post-translational modification or may fail to assemble properly into complexes. These aberrant proteins may form toxic aggregates within the cell and thus need to be eliminated. Impaired or dysregulated intracellular protein degradation can lead to a wide variety of disease states. Our laboratory is interested in elucidating the structural mechanism of proteins involved in three major protein degradation systems in cells: the AAA+ proteolytic machines, autophagy, and phagocytosis. We take an integrated structural biology approach combining X-ray crystallography, nuclear magnetic resonance spectroscopy (NMR), and electron microscopy (EM) single-particle structure determination methods. We hope that our work will lead to a better understanding of the action mechanisms of proteins involved in intracellular protein degradation, which may aid the design of novel therapeutic strategies for treating diseases.

Degrees and Positions Held
Positions Held
  • 2019 – present   Deputy Director, Institute of Biological Chemistry, Academia Sinica
  • 2019 – present   Research Fellow, Institute of Biological Chemistry, Academia Sinica
  • 2010 – present   Adjunct Associate Professor, Institute of Biochemical Sciences, College of Life Science, National Taiwan University
  • 2009 – 2019   Associate Research Fellow (Tenured 2014), Institute of Biological Chemistry, Academia Sinica
  • 2006 – 2009   Research Scientist, Array BioPharma Inc., Protein Biology Group
  • 2002 – 2006   HHMl Associate, Howard Hughes Medical Institute
Degrees
  • 1997 – 2002   Ph.D., Molecular Biophysics, University of Texas Southwestern Medical Center at Dallas
  • 1990 – 1992   M.S., Graduate Institute of Biochemistry and Molecular Biology, National Taiwan University College of Medicine
  • 1986 – 1990   B.S., School of Pharmacy, National Taiwan University College of Medicine
Selected Publications
Chueh CK, Som N, Ke LC, Ho MR, Reddy M, Chang CI
mBio (2019)
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)
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)
Lin, C.-C., Su, S.-C., Su, M.-Y., Liang, P.-H., Fang, C.-C., Wu, S.-H., and Chang, C.-I
Structure (2016)
Su MY, Peng WH, Ho MR, Su SC, Chang YC, Chen GC, Chang CI
Autophagy (2015)
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)
Ming-Yuan Su, Chiao-I Kuo, Chi-Fon Chang, Chung-I Chang
PLOS ONE (2013)
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
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY (2011)
Chang CI, Chelliah Y, Borek D, Mengin-Lecreulx D, Deisenhofer J.
Science (2006)
Publications List
  1. 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."
  2. 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."
  3. 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."
  4. 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."
  5. 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."
  6. 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."
  7. 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."
  8. 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."
  9. 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."
  10. 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."
  11. 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."
  12. 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"
  13. 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."
  14. 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"
  15. 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."
  16. 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"
  17. 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."
  18. 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."
  19. Chang CI, Deisenhofer J.  (2007)  Cell Mol Life Sci.  64, 1395-1402  "The peptidoglycan recognition proteins LCa and LCx."
  20. 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."
  21. 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."
  22. 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."
  23. Goldsmith EJ, Cobb MH, Chang CI.  (2004)  Methods in Molecular Biology  250, 127-144  "Structure of MAPKs."
  24. Goldsmith EJ, Chang CI.  (2002)  Structure  10, 888-889  "Another twist in helix C and a missing pocket."
  25. 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."

Intracellular protein degradation serves multiple vital functions in all living cells. For example, selective degradation of regulatory proteins such as transcription factors and cell cycle regulators allows rapid change in their concentration within the cell, which represents an effective form of regulation. Another important function of intracellular proteolysis is to rid the cell of potentially harmful proteins that are misfolded or damaged, which may be altered due to abnormal post-translational modification or may fail to assemble properly into complexes. These aberrant proteins may form toxic aggregates within the cell and thus need to be eliminated. Impaired or dysregulated intracellular protein degradation can lead to a wide variety of disease states. Our laboratory is interested in elucidating the structural mechanism of proteins involved in three major protein degradation systems in cells: the AAA+ proteolytic machines, autophagy, and phagocytosis. We take an integrated structural biology approach combining X-ray crystallography, nuclear magnetic resonance spectroscopy (NMR), and electron microscopy (EM) single-particle structure determination methods. We hope that our work will lead to a better understanding of the action mechanisms of proteins involved in intracellular protein degradation, which may aid the design of novel therapeutic strategies for treating diseases.

Positions Held
  • 2019 – present   Deputy Director, Institute of Biological Chemistry, Academia Sinica
  • 2019 – present   Research Fellow, Institute of Biological Chemistry, Academia Sinica
  • 2010 – present   Adjunct Associate Professor, Institute of Biochemical Sciences, College of Life Science, National Taiwan University
  • 2009 – 2019   Associate Research Fellow (Tenured 2014), Institute of Biological Chemistry, Academia Sinica
  • 2006 – 2009   Research Scientist, Array BioPharma Inc., Protein Biology Group
  • 2002 – 2006   HHMl Associate, Howard Hughes Medical Institute
Degrees
  • 1997 – 2002   Ph.D., Molecular Biophysics, University of Texas Southwestern Medical Center at Dallas
  • 1990 – 1992   M.S., Graduate Institute of Biochemistry and Molecular Biology, National Taiwan University College of Medicine
  • 1986 – 1990   B.S., School of Pharmacy, National Taiwan University College of Medicine
Chueh CK, Som N, Ke LC, Ho MR, Reddy M, Chang CI
mBio (2019)
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)
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)
Lin, C.-C., Su, S.-C., Su, M.-Y., Liang, P.-H., Fang, C.-C., Wu, S.-H., and Chang, C.-I
Structure (2016)
Su MY, Peng WH, Ho MR, Su SC, Chang YC, Chen GC, Chang CI
Autophagy (2015)
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)
Ming-Yuan Su, Chiao-I Kuo, Chi-Fon Chang, Chung-I Chang
PLOS ONE (2013)
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
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY (2011)
Chang CI, Chelliah Y, Borek D, Mengin-Lecreulx D, Deisenhofer J.
Science (2006)
  1. 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."
  2. 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."
  3. 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."
  4. 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."
  5. 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."
  6. 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."
  7. 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."
  8. 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."
  9. 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."
  10. 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."
  11. 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."
  12. 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"
  13. 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."
  14. 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"
  15. 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."
  16. 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"
  17. 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."
  18. 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."
  19. Chang CI, Deisenhofer J.  (2007)  Cell Mol Life Sci.  64, 1395-1402  "The peptidoglycan recognition proteins LCa and LCx."
  20. 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."
  21. 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."
  22. 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."
  23. Goldsmith EJ, Cobb MH, Chang CI.  (2004)  Methods in Molecular Biology  250, 127-144  "Structure of MAPKs."
  24. Goldsmith EJ, Chang CI.  (2002)  Structure  10, 888-889  "Another twist in helix C and a missing pocket."
  25. 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."