• HU Hongyu
  • Ph.D., Professor

    Professor of Biochemistry and Molecular Biology,

    State Key Laboratory of Molecular Biology,

    Shanghai Institute of Biochemistry and Cell Biology,

    Center for Excellence in Molecular Cell Science,

    Chinese Academy of Sciences,

    320 Yue-yang Road, Shanghai 200031, China.

    Tel: 86-021-54921121; FAX: 86-021-54921011.

  • E-mail:hyhu@@sibcb.ac.cn
    Research Areas
  • Protein Aggregation, Inclusion, Sequestration, Interaction, Phase Transition, Proteostasis, Proteinopathy;

    Cellular Homeostasis, Molecular Chaperone, Ubiquitin-Proteasome, Protein Degradation, RNA-Binding Protein, Ribostasis, Loss-of-Function, Cytotoxicity, Neurodegeneration;

    Cellular Biochemistry, Biochemical Techniques, Biophysical Techniques, Nuclear Magnetic Resonance,Fluorescence,Immunofluorescence Microscopy.

    Research Interests
  • The hallmark of some neurodegenerative diseases is the aggregation of abnormal proteins and formation of inclusion bodies in neural cells. The research group focuses on the mechanism of protein misfolding, amyloidogenic aggregation and sequestration, and phase transition of the cellular related proteins. Based on biochemical, structural and cellular information, we are trying to understand the proteinopathies of polyQ proteins and RNA-binding proteins associated with neurodegenerative diseases. The research areas are:

    (1) Mechanism of protein misfolding, aggregation and inclusion formation, phase transition, and their cellular effects;

    (2) Sequestration of cellular essential proteins by the protein aggregates and inclusions;

    (3) Proteostasis network of the amyloidogenic proteins associated with neurodegenerative diseases;

    (4) Structural basis for and functional annotation of the molecular recognition involved in proteostasis network and protein quality control.

    Selected Publications
    1. Wei Xue#, Shu-Xian Zhang#, Wen-Tian He, Jun-Ye Hong, Lei-Lei Jiang, and Hong-Yu Hu*, Domain interactions reveal auto-inhibition of the deubiquitinating enzyme USP19 and its activation by HSP90 in the modulation of huntingtin aggregation. Biochem J, 2020, 477(21): 4295–4312.
    2. Xiao-feng Zhuo, Jian Wang, Jing Zhang, Lei-lei Jiang, Hong-Yu Hu*, and Jun-xia Lu*, Solid-State NMR Reveals the Structural Transformation of the TDP-43 Amyloidogenic Region upon Fibrillation. JACS, 2020, 142(7): 3412-3421.
    3. Hui Yang#, Hong-Wei Yue#, Wen-Tian He, Jun-Ye Hong, Lei-Lei Jiang, and Hong-Yu Hu*, PolyQ-expanded huntingtin and ataxin-3 sequester ubiquitin adaptors hHR23B and UBQLN2 into aggregates via conjugated ubiquitin. FASEB J, 2018, 32 (6): 2923-2933.
    4. [R] Hui Yang and Hong-Yu Hu*, Sequestration of cellular interacting partners by protein aggregates: implication in a loss-of-function pathology. FEBS J, 2016, 283: 3705-3717.
    5. Hui Yang, Shuai Liu, Wen-Tian He, Jian Zhao, Lei-Lei Jiang and Hong-Yu Hu*, Aggregation of Polyglutamine-expanded Ataxin 7 Protein Specifically Sequesters Ubiquitin-specific Protease 22 and Deteriorates Its Deubiquitinating Function in the Spt-Ada-Gcn5- Acetyltransferase (SAGA) Complex. J Biol Chem, 2015, 290(36): 21996-22004.
    6. Hui Yang, Jing-Jing Li, Shuai Liu, Jian Zhao, Ya-Jun Jiang, Ai-Xin Song, and Hong-Yu Hu*, Aggregation of polyglutamine-expanded ataxin-3 sequesters its specific interacting partners into inclusions: Implication in a loss-of-function pathology. Sci Rep, 2014, 4: 6410.
    7. Yong-Guang Gao*, Hui Yang, Jian Zhao, Ya-Jun Jiang, and Hong-Yu Hu*, Autoinhibitory Structure of the WW Domain of HYPB/SETD2 Regulates Its Interaction with the Proline-Rich Region of Huntingtin. Structure, 2014, 22(3): 378-386.
    8. Shuai Liu, Hui Yang, Yu-Hang Zhang, Ai-Xin Song, and Hong-Yu Hu*, NEDD8 ultimate buster-1 long (NUB1L) protein promotes transfer of NEDD8 to proteasome for degradation through the P97UFD1/NPL4 complex. J Biol Chem, 2013, 288(43):31339-31349.
    9. Lei-Lei Jiang, Mei-Xia Che, Jian Zhao, Chen-Jie Zhou, Mu-Yun Xie, Hai-Yin Li, Jian-Hua He and Hong-Yu Hu*, Structural Transformation of the Amyloidogenic Core Region of TAR DNA Binding Protein of 43 kDa (TDP-43) Initiates Its Aggregation and Cytoplasmic Inclusion. J Biol Chem, 2013, 288(27): 19614-19624.
    10. Xue-Chao Gao, Chen-Jie Zhou, Zi-Ren Zhou, Meng Wu, Chun-Yang Cao and Hong- Yu Hu*, The C-terminal Helices of Heat Shock Protein 70 Are Essential for J-domain Binding and ATPase Activation. J Biol Chem, 2012, 287(8): 6044-6052.
    11. Ya-Jun Jiang, Mei-Xia Che, Jin-Qiao Yuan, Yuan-Yuan Xie, Xian-Zhong Yan, and Hong-Yu Hu*, Interaction with Polyglutamine Expanded Huntingtin Alters Cellular Distribution and RNA Processing of Huntingtin Yeast Two-hybrid Protein A (HYPA). J Biol Chem, 2011, 286 (28): 25236-25245.
    12. Mei-Xia Che, Ya-Jun Jiang, Yuan-Yuan Xie, Lei-Lei Jiang and Hong-Yu Hu*, Aggregation of the 35-kDa fragment of TDP-43 causes formation of cytoplasmic inclusions and alteration of RNA processing. FASEB J, 2011, 25 (7): 2344-2353.
    13. Xiao-Wei Zhang, Xiao-Jing Yan, Zi-Ren Zhou, Fei-Fei Yang, Zi-Yu Wu,Hong-Bin Sun, Wen-Xue Liang, Ai-Xing Song, Lallemand-Breitenbach Valerie, Jeanne Marion, Qun-Ye Zhang, Huai-Yu Yang, Qiu-Hua Huang, Guang-Biao Zhou, Jian-Hua Tong, Yan Zhang, Ji-Hui Wu, Hong-Yu Hu, Hugues de Thé, Sai-Juan Chen*, Zhu Chen*, The Leukemia Drug Arsenic Trioxide Controls the Fate of the PML-RARa Oncoprotein by Directly Binding PML. Science, 2010, 328: 240-243.
    14. Yuan-Yuan Xie, Chen-Jie Zhou, Zi-Ren Zhou, Jing Hong, Mei-Xia Che, Qing-Shan Fu, Ai-Xin Song, Dong-Hai Lin, and Hong-Yu Hu*, Interaction with synphilin-1 promotes inclusion formation of a-synuclein: Mechanistic insights and pathological implication. FASEB J, 2010, 24 (1): 196-205.
    15. Qing-Shan Fu, Chen-Jie Zhou, Hong-Chang Gao, Ya-Jun Jiang, Zi-Ren Zhou, Jing Hong, Wen-Ming Yao, Ai-Xin Song, Dong-Hai Lin*, andHong-Yu Hu*, Structural Basis for Ubiquitin Recognition by a Novel Domain from Human Phospholipase A2 Activating Protein. J Biol Chem, 2009, 284 (28): 19043-19052.
    16. Yong-Gang Chang, Xian-Zhong Yan, Yuan-Yuan Xie, Xue-Chao Gao, Ai-Xin Song, Dong-Er Zhang and Hong-Yu Hu*, Different Roles for Two Ubiquitin-like Domains of ISG15 in Protein Modification. J Biol Chem, 2008, 283 (19): 13370-13377.
    17. Yong-Guang Gao, Xian-Zhong Yan*, Ai-Xin Song, Yong-Gang Chang, Xue-Chao Gao, Nan Jiang, Qi Zhang, and Hong-Yu Hu*, Structural insights into the specific binding of huntingtin proline-rich region with SH3 and WW domains. Structure, 2006, 14 (12): 1755-1765.
    18. Hong-Tao Li, Dong-Hai Lin, Xiao-Ying Luo, Feng Zhang, Li-Na Ji, Hai-Ning Du, Guo-Qiang Song, Jun Hu, Jia-Wei Zhou and Hong-Yu Hu*. Inhibition of α-synuclein fibrillization by dopamine analogs via reaction with the amino groups of α-synuclein: Implication for dopaminergic neurodegeneration. FEBS J, 2005, 272 (14): 3661-3672.
    19. Hong-Yu Hu, Julie K. Horton, Michael R. Gryk, Rajendra Prasad, Jana M Naron, Di-An Sun, Sidney M. Hecht, Samuel H. Wilson*, Gregory P Mullen, Identification of small molecule synthetic inhibitors of DNA polymerase beta by NMR chemical shift mapping. J Biol Chem, 2004, 279 (38): 39736-39744.
    20. Hai-Ning Du, Lin Tang, Xiao-Ying Luo, Hong-Tao Li, Jun Hu, Jia-Wei Zhou, and Hong-Yu Hu*, A peptide motif consisting of glycine, alanine and valine is required for fibrillization and cytotoxicity of human a-synuclein. Biochemistry, 2003, 42 (29): 8870-8878.
    Education Background & Academic Experience
  • Resume

    1987, B.S., Department of Biology, Fudan University;

    1990, M.S., Department of Chemistry, Fudan University;

    1993, Ph. D., Shanghai Institute of Biochemistry, Chinese Academy of Sciences;

    1993-1994, Assistant Professor, Shanghai Institute of Biochemistry, Chinese Academy of Sciences;

    1994-1996, Postdoctoral, Department of Biochemistry, the Hong Kong University of Science & Technology, Hong Kong;

    1996-2000, Associate Professor, Shanghai Institute of Biochemistry, Chinese Academy of Sciences;

    2000, Visiting Scholar, Laboratory of NMR Structural Biology, Department of Biochemistry, University of Connecticut Health Center, USA;

    2001-2019, Professor, Institute of Biochemistry & Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences;

    2002-2003, Visiting Scholar, the Hong Kong University of Science & Technology, Hong Kong;

    2004, Visiting Scholar, Department of Molecular and Experimental Medicine, The Scripps Research Institute, USA;

    2020-present, Professor, Shanghai Institute of Biochemistry & Cell Biology, Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences.


    Academic Activities

    Council Member of the Chinese Molecular Biophysics Society (2011—)

    Council Member of the Shanghai Society of Biochemistry and Molecular Biology (2011—2018)

    Council Member of the Chinese Protein Society (2006 —2015);

    Council Member of the Chinese Society of Biochemistry and Molecular Biology (2005—2014);

    Editorial Board Member of Protein & Peptide Letters (2005—);

    Editorial Board Member of Acta Biochem Biophys Sinica (2007—);

    Editorial Board Member of Scientific Reports (2015—).