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MAO Youdong

  • Professor, Doctoral Supervisor
  • Boya Distinguished Professor, School of Physics, Peking University
    Center for Quantitative Biology, Peking University
    Center for Life Sciences, Peking University and Tsinghua University
    National Biomedical Imaging Center, Peking University
    Head of the Multimodal Transscale Biomedical Imaging Science Facility
  • 个人简介
    Dr. Mao is currently Full Professor with Tenure at School of Physics, Peking University. The Mao Laboratory focuses on the mechanistic investigation of ubiquitin-proteasome system (UPS) and its regulation of essential intracellular processes by leveraging multidisciplinary approaches in physical biology. The major research topics currently being conducted in the laboratory are of three folds:

    (1) We are developing novel AI-based classification algorithms for high-resolution 4D cryo-EM to reconstitute non-equilibrium dynamics of complex assembly. These novel approaches are applied to study how the proteasome is regulated at multiple levels by cellular proteins and how the UPS regulates important physiological processes involved in inflammation, carcinogenesis, neurodegeneration, viral infection, and metabolism.

    (2) We are developing novel machine learning approaches for dynamics-based drug discovery and vaccine immunogen design. These methods are used to design new compounds targeting the UPS based on structural dynamics information obtained from high-resolution cryo-EM analysis.

    (3) By targeting key components of the UPS, we are innovating multidisciplinary methods for designing molecular glue and for degradation-based therapeutics in combating cancer, neurodegenerative and cardiovascular diseases.
  • 所授课程
    Special Topics in Molecular Biophysics and Cryoelectron Microscopy (Elective, 2 credits)
  • 获奖及荣誉
    Winner of National Science Fund for Distinguished Young Scholars
  • 个人履历
    2022-present Boya Tenured Professor, Researcher, Institute of Condensed Matter, School of Physics, Peking University
    2021-2022 Tenured Associate Professor, Researcher, Institute of Condensed Matter, School of Physics, Peking University
    2016-present Researcher, Center of Quantitative Biology, Peking University, doctoral supervisor
    2015-2020 Assistant Professor, Institute of Condensed Matter, School of Physics, Peking University
    2012-2015 Principal Investigator, Intel Center for Parallel Computing Structural Biology, Dana-Farber Cancer Institute, Harvard Medical School
    2007-2012 Postdoctoral Researcher, Harvard Medical School
    2005-2007 Postdoctoral Researcher, National Center for Nanoscience, Chinese Academy of Sciences
    1999-2005 School of Physics, Peking University, Ph.D. in Condensed Matter
    1995-1999 School of Physics, Wuhan University, Bachelor of Science, Physics major
  • 代表性论文及论著
    1. Zhang S#, Zou S#, Yin D, Zhao L, Finley D, Wu Z, Mao Y*. USP14-regulated allostery of the human proteasome by time-resolved cryo-EM. Nature 2022; 605: 567-574.
    2. Zhang S#, Wang K#, Wang WL#, Nguyen HT, Chen S, Lu M, Go EP, Ding H, Steinbock RT, Desaire H, Kappes JC, Sodroski J*, Mao Y*. Asymmetric structures and conformational plasticity of the uncleaved full-length human immunodeficiency virus (HIV-1) envelope glycoprotein trimer. J. Virol. 2021; 95: e00529-21.
    3. Sharif H#, Wang L#, Wang WL#, Magupalli VG, Andreeva L, Qiao Q, Hauenstein AV, Wu Z, Nunez G, Mao Y*, Wu H*. Structural mechanism for NEK7-licensed NLRP3 inflammasome activation. Nature 2019; 570: 338-343.
    4. Dong Y#, Zhang S#, Wu Z, Li X, Wang W, Zhu Y, Stoilova-McPhie S, Lu Y, Finley D, Mao Y*. Cryo-EM structures and dynamics of substrate-engaged human 26S proteasome. Nature 2019; 565: 49-55.
    5. Lu Y#, Wu J#, Dong Y, Chen S, Sun S, Ma YB, Ouyang Q, Finley D, Kirschner MW*, Mao Y*. Conformational landscape of the p28-bound human proteasome regulatory particle. Mol. Cell 2017; 67: 322-333.e6.
    6. Zhang L#, Chen S#, Ruan J, Wu J, Tong AB, Yin Q, Li Y, David L, Lu A, Wang WL, Marks C, Ouyang Q, Zhang X, Mao Y*, Wu H*. Cryo-EM structure of the activated NAIP2-NLRC4 inflammasome reveals nucleated polymerization. Science 2015; 350: 404-409.
    7. Wu Z, Chen E, Zhang S, Ma Y, Mao Y*. Visualizing conformational space of functional biomolecular complexes by deep manifold learning. Int. J. Mol. Sci. 2022; 23: 8872.
    8. ​Dong Y, Chen S, Zhang S, Sodroski J, Yang Z, Liu D, Mao Y*. Folding DNA into a lipid-conjugated nanobarrel for controlled reconstitution of membrane proteins. Angew. Chem. Int. Ed. 2018; 57: 2072-2076.
    9. Wu J, Ma Y, Congdon C, Brett B, Chen S, Ouyang Q, Mao Y*. Massively parallel unsupervised single-particle cryo-EM data clustering via statistical manifold learning. PLoS One 2017; 12: e0182130.
    10. Zhu Y, Ouyang Q, Mao Y*. A deep convolutional neural network approach to single-particle recognition in cryo-electron microscopy. BMC Bioinformatics 2017; 18: 348.