研究領域與專長

泛素與其相關之結構生物研究

後轉錄修飾在生物體內扮演了相當重要的功能調控角色。 舉凡磷酸修飾、甲基修飾、醣修飾等都是使用小分子直接在蛋白質的特定位置進行修飾。 然而泛素(ubiquitin)標記反應直接採用一個76顆氨基酸的小蛋白質(泛素)修飾在特定蛋白質上面。近半人體內的蛋白質都會被泛素修飾,絕大部分的泛素修飾產物會被帶往細胞內的蛋白酶體處理,如同細胞內的碎紙機把蛋白質絞碎後,回收氨基酸再利用。

在先天免疫(innate immune)系統中,有一種不同於一般的泛素修飾系統。這組特別的類泛素系統專責對抗病毒及細菌的侵襲。這是人體免疫系統中第一道防禦戰線,HERC5是這組類泛素系統中負責把類泛素(ISG15)標記在病毒跟病菌帶原體上的蛋白質的關鍵E3酵素。舉例來說,感冒病毒、登革熱病毒或是茲卡病毒在侵入免疫系統後,干擾素活化的HERC5會啟動一系列的抗禦機制促使免疫系統代謝外來病原體的NS1蛋白,最終有效降低病毒或病菌的增生效率。

免疫系統的類泛素反應的細節有待釐清,藉由運用多種結構生物學先進儀器(低溫電子顯微鏡、同步輻射繞射器以及核磁共振儀),探討蛋白質的細微互動,標定酵素反應的調控中心可提供結構生物學導向的的藥物設計以利抵抗病原體的感染。

學經歷
經歷
  • 2018 – 迄今   助研究員, 中央研究院生物化學研究所
  • 2018 – 2018   客座助理教授, 中央研究院生物化學研究所
  • 2017 – 2018   助理研究學者, 科技部
  • 2012 – 2017   博士後研究學者, 美國聖猶大兒童研究醫院結構生物部門
  • 2010 – 2012   博士後研究學者, 美國新澤西州立羅格斯大學先進生物科技與醫藥中心
學歷
  • 2004 – 2010   博士, 化學系, 美國新澤西州立羅格斯大學
  • 2000 – 2002   碩士, 生命科學研究所, 國立清華大學
  • 1996 – 2000   學士, 生命科學系, 國立清華大學
主要著作
Mulder MP, Witting K, Berlin I, Pruneda JN, Wu KP, Chang JG, Merkx R, Bialas J, Groettrup M, Vertegaal AC, Schulman BA, Komander D, Neefjes J, El Oualid F, Ovaa H
Nature Chemical Biology (2016)
Brown NG, VanderLinden R, Watson ER, Weissmann F, Ordureau A, Wu KP, Zhang W, Yu S, Mercredi PY, Harrison JS, Davidson IF, Qiao R, Lu Y, Dube P, Brunner MR, Grace CRR, Miller DJ, Haselbach D, Jarvis MA, Yamaguchi M, Yanishevski D, Petzold G, Sidhu SS, Kuhlman B, Kirschner MW, Harper JW, Peters JM, Stark H, Schulman BA
Cell (2016)
Zhang W, Wu KP, Sartori MA, Kamadurai HB, Ordureau A, Jiang C, Mercredi PY, Murchie R, Hu J, Persaud A, Mukherjee M, Li N, Doye A, Walker JR, Sheng Y, Hao Z, Li Y, Brown KR, Lemichez E, Chen J, Tong Y, Harper JW, Moffat J, Rotin D, Schulman BA, Sidhu SS
Molecular Cell (2016)
Janowska MK, Wu KP, Baum J
Scientific Reports (2015)
Kim S, Wu KP, Baum J
Journal of Biomolecular NMR (2013)
Wu KP, Baum J
Journal of American Chemistry Society (2010)
Wu KP, Weinstock DS, Narayanan C, Levy RM, Baum J
Journal of Molecular Biology (2009)
著作列表
  1. Yang TJ, Chang YC, Ko TP, Draczkowski P, Chien YC, Chang YC, (Wu KP), Khoo KH, Chang HW, Hsu STD  (2020-01)  Proceedings of the National Academy of Sciences of the United States of America  117(3),1438-1446  "Cryo-EM analysis of a feline coronavirus spike protein reveals a unique structure and camouflaging glycans."
  2. Qiu Y, Zheng Y, (Wu KP), Schulman BA  (2017)  Protein science : a publication of the Protein Society  26(8), 1674-1680  "Insights into links between autophagy and the ubiquitin system from the structure of LC3B bound to the LIR motif from the E3 ligase NEDD4."
  3. Mulder MP, Witting K, Berlin I, Pruneda JN, (Wu KP), Chang JG, Merkx R, Bialas J, Groettrup M, Vertegaal AC, Schulman BA, Komander D, Neefjes J, El Oualid F, Ovaa H  (2016-07)  Nature chemical biology  12(7), 523-530  "A cascading activity-based probe sequentially targets E1-E2-E3 ubiquitin enzymes."
  4. Brown NG, VanderLinden R, Watson ER, Weissmann F, Ordureau A, (Wu KP), Zhang W, Yu S, Mercredi PY, Harrison JS, Davidson IF, Qiao R, Lu Y, Dube P, Brunner MR, Grace CRR, Miller DJ, Haselbach D, Jarvis MA, Yamaguchi M, Yanishevski D, Petzold G, Sidhu SS, Kuhlman B, Kirschner MW, Harper JW, Peters JM, Stark H, Schulman BA  (2016-06)  Cell  165(6), 1440-1453  "Dual RING E3 Architectures Regulate Multiubiquitination and Ubiquitin Chain Elongation by APC/C."
  5. Zhang W, (Wu KP), Sartori MA, Kamadurai HB, Ordureau A, Jiang C, Mercredi PY, Murchie R, Hu J, Persaud A, Mukherjee M, Li N, Doye A, Walker JR, Sheng Y, Hao Z, Li Y, Brown KR, Lemichez E, Chen J, Tong Y, Harper JW, Moffat J, Rotin D, Schulman BA, Sidhu SS  (2016-04)  Molecular cell  62(1), 121-136  "System-Wide Modulation of HECT E3 Ligases with Selective Ubiquitin Variant Probes."
  6. Fang NN, Zhu M, Rose A, (Wu KP), Mayor T  (2016)  Nature communications  7, 12907  "Deubiquitinase activity is required for the proteasomal degradation of misfolded cytosolic proteins upon heat-stress."
  7. Janowska MK, (Wu KP), Baum J  (2015-10)  Scientific reports  5, 15164  "Unveiling transient protein-protein interactions that modulate inhibition of alpha-synuclein aggregation by beta-synuclein, a pre-synaptic protein that co-localizes with alpha-synuclein."
  8. Riling C, Kamadurai H, Kumar S, O'Leary CE, (Wu KP), Manion EE, Ying M, Schulman BA, Oliver PM  (2015)  The Journal of biological chemistry  290(39), 23875-87  "Itch WW Domains Inhibit Its E3 Ubiquitin Ligase Activity by Blocking E2-E3 Ligase Trans-thiolation."
  9. Kim S, (Wu KP), Baum J  (2013-03)  Journal of biomolecular NMR  55(3), 249-256  "Fast hydrogen exchange affects (1)(5)N relaxation measurements in intrinsically disordered proteins."
  10. Park JH, Yoshizumi S, Yamaguchi Y, (Wu KP), Inouye M  (2013)  Proteins  81(5), 874-83  "ACA-specific RNA sequence recognition is acquired via the loop 2 region of MazF mRNA interferase."
  11. Narayanan C, Weinstock DS, (Wu KP), Baum J, Levy RM  (2012)  Journal of chemical theory and computation  8(10), 3929-3942  "Investigation of the Polymeric Properties of alpha-Synuclein and Comparison with NMR Experiments: A Replica Exchange Molecular Dynamics Study."
  12. Kobayashi H, Swapna GV, (Wu KP), Afinogenova Y, Conover K, Mao B, Montelione GT, Inouye M  (2012)  Journal of biomolecular NMR  52(4), 303-13  "Segmental isotope labeling of proteins for NMR structural study using a protein S tag for higher expression and solubility."
  13. Masuda H, Tan Q, Awano N, (Wu KP), Inouye M  (2012)  Molecular microbiology  84(5), 979-89  "YeeU enhances the bundling of cytoskeletal polymers of MreB and FtsZ, antagonizing the CbtA (YeeV) toxicity in Escherichia coli."
  14. (Wu KP), Baum J  (2011)  Biomolecular NMR assignments  5(1), 43-6  "Backbone assignment and dynamics of human alpha-synuclein in viscous 2 M glucose solution."
  15. Kang L, (Wu KP), Vendruscolo M, Baum J  (2011)  Journal of the American Chemical Society  133(34), 13465-70  "The A53T mutation is key in defining the differences in the aggregation kinetics of human and mouse alpha-synuclein."
  16. (Wu KP), Baum J  (2010-04)  Journal of the American Chemical Society  132(16), 5546-5547  "Detection of transient interchain interactions in the intrinsically disordered protein alpha-synuclein by NMR paramagnetic relaxation enhancement."
  17. (Wu KP), Weinstock DS, Narayanan C, Levy RM, Baum J  (2009-08)  Journal of molecular biology  391(4), 784-796  "Structural reorganization of alpha-synuclein at low pH observed by NMR and REMD simulations."
  18. (Wu KP), Kim S, Fela DA, Baum J  (2008)  Journal of molecular biology  378(5), 1104-15  "Characterization of conformational and dynamic properties of natively unfolded human and mouse alpha-synuclein ensembles by NMR: implication for aggregation."
  19. Weinstock DS, Narayanan C, Felts AK, Andrec M, Levy RM, (Wu KP), Baum J  (2007)  Journal of the American Chemical Society  129(16), 4858-9  "Distinguishing among structural ensembles of the GB1 peptide: REMD simulations and NMR experiments."
  20. Pan YR, Wu KP, Lou YC, Liao YD, Chen C  (2005)  Journal of biomolecular NMR  31(2), 175-6  "1H, 13C and 15N resonance assignments and secondary structure of murine angiogenin 4."
  21. Wang I, Lou YC, (Wu KP), Wu SH, Chang WC, Chen C  (2005)  Journal of molecular biology  346(4), 1071-82  "Novel solution structure of porcine beta-microseminoprotein."
  22. (Wu KP), Wu CW, Tsao YP, Kuo TW, Lou YC, Lin CW, Wu SC, Cheng JW  (2003)  The Journal of biological chemistry  278(46), 46007-13  "Structural basis of a flavivirus recognized by its neutralizing antibody: solution structure of the domain III of the Japanese encephalitis virus envelope protein."

泛素與其相關之結構生物研究

後轉錄修飾在生物體內扮演了相當重要的功能調控角色。 舉凡磷酸修飾、甲基修飾、醣修飾等都是使用小分子直接在蛋白質的特定位置進行修飾。 然而泛素(ubiquitin)標記反應直接採用一個76顆氨基酸的小蛋白質(泛素)修飾在特定蛋白質上面。近半人體內的蛋白質都會被泛素修飾,絕大部分的泛素修飾產物會被帶往細胞內的蛋白酶體處理,如同細胞內的碎紙機把蛋白質絞碎後,回收氨基酸再利用。

在先天免疫(innate immune)系統中,有一種不同於一般的泛素修飾系統。這組特別的類泛素系統專責對抗病毒及細菌的侵襲。這是人體免疫系統中第一道防禦戰線,HERC5是這組類泛素系統中負責把類泛素(ISG15)標記在病毒跟病菌帶原體上的蛋白質的關鍵E3酵素。舉例來說,感冒病毒、登革熱病毒或是茲卡病毒在侵入免疫系統後,干擾素活化的HERC5會啟動一系列的抗禦機制促使免疫系統代謝外來病原體的NS1蛋白,最終有效降低病毒或病菌的增生效率。

免疫系統的類泛素反應的細節有待釐清,藉由運用多種結構生物學先進儀器(低溫電子顯微鏡、同步輻射繞射器以及核磁共振儀),探討蛋白質的細微互動,標定酵素反應的調控中心可提供結構生物學導向的的藥物設計以利抵抗病原體的感染。

經歷
  • 2018 – 迄今   助研究員, 中央研究院生物化學研究所
  • 2018 – 2018   客座助理教授, 中央研究院生物化學研究所
  • 2017 – 2018   助理研究學者, 科技部
  • 2012 – 2017   博士後研究學者, 美國聖猶大兒童研究醫院結構生物部門
  • 2010 – 2012   博士後研究學者, 美國新澤西州立羅格斯大學先進生物科技與醫藥中心
學歷
  • 2004 – 2010   博士, 化學系, 美國新澤西州立羅格斯大學
  • 2000 – 2002   碩士, 生命科學研究所, 國立清華大學
  • 1996 – 2000   學士, 生命科學系, 國立清華大學
Mulder MP, Witting K, Berlin I, Pruneda JN, Wu KP, Chang JG, Merkx R, Bialas J, Groettrup M, Vertegaal AC, Schulman BA, Komander D, Neefjes J, El Oualid F, Ovaa H
Nature Chemical Biology (2016)
Brown NG, VanderLinden R, Watson ER, Weissmann F, Ordureau A, Wu KP, Zhang W, Yu S, Mercredi PY, Harrison JS, Davidson IF, Qiao R, Lu Y, Dube P, Brunner MR, Grace CRR, Miller DJ, Haselbach D, Jarvis MA, Yamaguchi M, Yanishevski D, Petzold G, Sidhu SS, Kuhlman B, Kirschner MW, Harper JW, Peters JM, Stark H, Schulman BA
Cell (2016)
Zhang W, Wu KP, Sartori MA, Kamadurai HB, Ordureau A, Jiang C, Mercredi PY, Murchie R, Hu J, Persaud A, Mukherjee M, Li N, Doye A, Walker JR, Sheng Y, Hao Z, Li Y, Brown KR, Lemichez E, Chen J, Tong Y, Harper JW, Moffat J, Rotin D, Schulman BA, Sidhu SS
Molecular Cell (2016)
Janowska MK, Wu KP, Baum J
Scientific Reports (2015)
Kim S, Wu KP, Baum J
Journal of Biomolecular NMR (2013)
Wu KP, Baum J
Journal of American Chemistry Society (2010)
Wu KP, Weinstock DS, Narayanan C, Levy RM, Baum J
Journal of Molecular Biology (2009)
  1. Yang TJ, Chang YC, Ko TP, Draczkowski P, Chien YC, Chang YC, (Wu KP), Khoo KH, Chang HW, Hsu STD  (2020-01)  Proceedings of the National Academy of Sciences of the United States of America  117(3),1438-1446  "Cryo-EM analysis of a feline coronavirus spike protein reveals a unique structure and camouflaging glycans."
  2. Qiu Y, Zheng Y, (Wu KP), Schulman BA  (2017)  Protein science : a publication of the Protein Society  26(8), 1674-1680  "Insights into links between autophagy and the ubiquitin system from the structure of LC3B bound to the LIR motif from the E3 ligase NEDD4."
  3. Mulder MP, Witting K, Berlin I, Pruneda JN, (Wu KP), Chang JG, Merkx R, Bialas J, Groettrup M, Vertegaal AC, Schulman BA, Komander D, Neefjes J, El Oualid F, Ovaa H  (2016-07)  Nature chemical biology  12(7), 523-530  "A cascading activity-based probe sequentially targets E1-E2-E3 ubiquitin enzymes."
  4. Brown NG, VanderLinden R, Watson ER, Weissmann F, Ordureau A, (Wu KP), Zhang W, Yu S, Mercredi PY, Harrison JS, Davidson IF, Qiao R, Lu Y, Dube P, Brunner MR, Grace CRR, Miller DJ, Haselbach D, Jarvis MA, Yamaguchi M, Yanishevski D, Petzold G, Sidhu SS, Kuhlman B, Kirschner MW, Harper JW, Peters JM, Stark H, Schulman BA  (2016-06)  Cell  165(6), 1440-1453  "Dual RING E3 Architectures Regulate Multiubiquitination and Ubiquitin Chain Elongation by APC/C."
  5. Zhang W, (Wu KP), Sartori MA, Kamadurai HB, Ordureau A, Jiang C, Mercredi PY, Murchie R, Hu J, Persaud A, Mukherjee M, Li N, Doye A, Walker JR, Sheng Y, Hao Z, Li Y, Brown KR, Lemichez E, Chen J, Tong Y, Harper JW, Moffat J, Rotin D, Schulman BA, Sidhu SS  (2016-04)  Molecular cell  62(1), 121-136  "System-Wide Modulation of HECT E3 Ligases with Selective Ubiquitin Variant Probes."
  6. Fang NN, Zhu M, Rose A, (Wu KP), Mayor T  (2016)  Nature communications  7, 12907  "Deubiquitinase activity is required for the proteasomal degradation of misfolded cytosolic proteins upon heat-stress."
  7. Janowska MK, (Wu KP), Baum J  (2015-10)  Scientific reports  5, 15164  "Unveiling transient protein-protein interactions that modulate inhibition of alpha-synuclein aggregation by beta-synuclein, a pre-synaptic protein that co-localizes with alpha-synuclein."
  8. Riling C, Kamadurai H, Kumar S, O'Leary CE, (Wu KP), Manion EE, Ying M, Schulman BA, Oliver PM  (2015)  The Journal of biological chemistry  290(39), 23875-87  "Itch WW Domains Inhibit Its E3 Ubiquitin Ligase Activity by Blocking E2-E3 Ligase Trans-thiolation."
  9. Kim S, (Wu KP), Baum J  (2013-03)  Journal of biomolecular NMR  55(3), 249-256  "Fast hydrogen exchange affects (1)(5)N relaxation measurements in intrinsically disordered proteins."
  10. Park JH, Yoshizumi S, Yamaguchi Y, (Wu KP), Inouye M  (2013)  Proteins  81(5), 874-83  "ACA-specific RNA sequence recognition is acquired via the loop 2 region of MazF mRNA interferase."
  11. Narayanan C, Weinstock DS, (Wu KP), Baum J, Levy RM  (2012)  Journal of chemical theory and computation  8(10), 3929-3942  "Investigation of the Polymeric Properties of alpha-Synuclein and Comparison with NMR Experiments: A Replica Exchange Molecular Dynamics Study."
  12. Kobayashi H, Swapna GV, (Wu KP), Afinogenova Y, Conover K, Mao B, Montelione GT, Inouye M  (2012)  Journal of biomolecular NMR  52(4), 303-13  "Segmental isotope labeling of proteins for NMR structural study using a protein S tag for higher expression and solubility."
  13. Masuda H, Tan Q, Awano N, (Wu KP), Inouye M  (2012)  Molecular microbiology  84(5), 979-89  "YeeU enhances the bundling of cytoskeletal polymers of MreB and FtsZ, antagonizing the CbtA (YeeV) toxicity in Escherichia coli."
  14. (Wu KP), Baum J  (2011)  Biomolecular NMR assignments  5(1), 43-6  "Backbone assignment and dynamics of human alpha-synuclein in viscous 2 M glucose solution."
  15. Kang L, (Wu KP), Vendruscolo M, Baum J  (2011)  Journal of the American Chemical Society  133(34), 13465-70  "The A53T mutation is key in defining the differences in the aggregation kinetics of human and mouse alpha-synuclein."
  16. (Wu KP), Baum J  (2010-04)  Journal of the American Chemical Society  132(16), 5546-5547  "Detection of transient interchain interactions in the intrinsically disordered protein alpha-synuclein by NMR paramagnetic relaxation enhancement."
  17. (Wu KP), Weinstock DS, Narayanan C, Levy RM, Baum J  (2009-08)  Journal of molecular biology  391(4), 784-796  "Structural reorganization of alpha-synuclein at low pH observed by NMR and REMD simulations."
  18. (Wu KP), Kim S, Fela DA, Baum J  (2008)  Journal of molecular biology  378(5), 1104-15  "Characterization of conformational and dynamic properties of natively unfolded human and mouse alpha-synuclein ensembles by NMR: implication for aggregation."
  19. Weinstock DS, Narayanan C, Felts AK, Andrec M, Levy RM, (Wu KP), Baum J  (2007)  Journal of the American Chemical Society  129(16), 4858-9  "Distinguishing among structural ensembles of the GB1 peptide: REMD simulations and NMR experiments."
  20. Pan YR, Wu KP, Lou YC, Liao YD, Chen C  (2005)  Journal of biomolecular NMR  31(2), 175-6  "1H, 13C and 15N resonance assignments and secondary structure of murine angiogenin 4."
  21. Wang I, Lou YC, (Wu KP), Wu SH, Chang WC, Chen C  (2005)  Journal of molecular biology  346(4), 1071-82  "Novel solution structure of porcine beta-microseminoprotein."
  22. (Wu KP), Wu CW, Tsao YP, Kuo TW, Lou YC, Lin CW, Wu SC, Cheng JW  (2003)  The Journal of biological chemistry  278(46), 46007-13  "Structural basis of a flavivirus recognized by its neutralizing antibody: solution structure of the domain III of the Japanese encephalitis virus envelope protein."