SMART Investigator
SMART Investigator
首页 Research SMART Investigator
Xueming Li

SMART Investigator

Affiliation

Tsinghua University

Research Area

The development of methods and techniques for cryo-electron microscopy, as well as related application research

Email

lixueming(at)tsinghua.edu.cn

Research Interests

Xueming‌ ‌Li primarily focuses on theoretical and methodological research in ‌cryo-electron microscopy (cryoEM)‌ and cryo-electron tomography(cryoET). His work emphasizes the development and application of the latest ‌cryo-EM techniques‌ to achieve ‌high-resolution three-dimensional (3D) reconstruction‌ of biological structures, advancing our capability to observe and study life processes at the ‌atomic level‌. Concurrently, he is dedicated to applying ‌electron microscopy‌ to biological research to address significant biological questions related to bio-macromolecular structures. The long-term goal of Li’s research aims to advance next-generation cryoEM instrumentation and methodologies. By integrating experimental techniques, ‌image processing and analysis‌, and ‌artificial intelligence (AI)‌, he seeks to characterize structures spanning from tissues to cells at ‌nanometer‌ and even ‌atomic resolution‌. This approach will enable us to understand the essence of life processes at the ‌atomic and molecular level‌, while simultaneously driving the application of ‌cryoEM technology‌ in areas such as ‌drug design‌ and healthcare.


Xueming Li has long been engaged in research on CryoEM. In 2013, Xueming Li made breakthroughs in his research on electron counting camera and drift correction algorithms, contributing significantly to the "Resolution Revolution" in CryoEM. Li was also among the early researchers to introduce general-purpose graphics processing units (GPUs) into the field of cryoEM. After returning to China in 2014, Xueming Li introduced multiple advanced technologies from other fields, including deep learning in artificial intelligence and particle filtering algorithms in electronic engineering. He also developed a series of new techniques for microcrystal diffraction(MicroED).  


In recent years, Xueming Li's laboratory has gradually shifted its focus to cryo-electron tomography for cells and their applications. The lab has developed a series of cellular structural analysis techniques involving tissue sample preparation and localization, in situ detection of biomacromolecules in cells, and three-dimensional reconstruction methods. Xueming Li has published over 60 research articles, including nearly 30 as corresponding or co-corresponding author in top journals such as Nature and its sister journals, Structure, and JSB. The technologies he has developed have been granted five patents.

Academic Training

2005/07–2009/03, Institute of Physics, Chinese Academy of Sciences, Ph.D. in Condensed Matter Physics  

2002/09–2005/07, University of Science and Technology Beijing, M.S. in Materials Physics and Chemistry  

1998/09–2002/07, University of Science and Technology Beijing, B.S. in Materials Physics

Employment

2019/07–Present, School of Life Sciences, Tsinghua University, Tenured Associate Professor  

2017/07–2019/07, School of Life Sciences, Tsinghua University, Tenure-track Associate Professor  

2014/01–2017/07, School of Life Sciences, Tsinghua University, Tenure-track Assistant Professor  

2009/04–2013/12, University of California, San Francisco, Postdoctoral Researcher  

Research Achievements

2024/04, First Prize of Beijing Science and Technology Award (Second Contributor)

2023/12, Second Prize of Natural Science Award by China Society of Image and Graphics (Fourth Contributor) 

2019/10, Third Prize of Natural Science Award under Wu Wenjun AI Science and Technology Award (Second Contributor) 

2015/09, Qiushi Outstanding Young Scholar Award

Representative Publications

1. Xiaofeng Yan#, Shudong Li, Weilin Huang, Hao Wang, Tianfang Zhao, Mingtao Huang, Niyun Zhou, Yuan Shen, Xueming Li*. MPicker: Visualizing and Picking Membrane Proteins for Cryo-Electron Tomography. Nature Communications, 2025, 16, 472. DOI: 10.1038/s41467-024-55767-w.


2. Ranhao Zhang#, Yuan Shen*, Xueming Li*. Tilt-series-based joint CTF estimation for cryo-electron tomography. Structure, 2024, 32, 1239-47.


3. Chao Lin#, Li Zhang#, Ziying Zhang#, Yifeng Jiang#, Xueming Li*. Locating cellular contents during cryoFIB milling using cellular secondary-electron imaging. Journal of Structural Biology, 2023, 215, 108005.


4. Keke Qu#, Kangjing Chen#, Hao Wang#, Xueming Li*, Zhucheng Chen*. Structure of the NuA4 acetyltransferase complex bound to the nucleosome. Nature, 2022, 610, 569-574.


5. Xuzhong Yang#, Chao Lin#, Xudong Chen#, Shouqin Li#, Xueming Li*, Bailong Xiao*, Structure deformation and curvature sensing of PIEZO1 in lipid membranes, Nature, 2022, 604, 377-383


6. Xinyu Zhang#, Tianfang Zhao#, Jiansheng Chen*, Yuan Shen*, Xueming Li*, EPicker is an exemplar-based continual learning approach for knowledge accumulation in cryoEM particle picking, Nature Communications, 2022, 13, 2468


7. Li Wang#, Heng Zhou#, Mingmin Zhang#, Wenhao Liu#, Tuan Deng, Qiancheng Zhao, Yiran Li, Jianlin Lei, Xueming Li*, Bailong Xiao*, Structure and mechanogating of the mammalian tactile channel PIEZO2, Nature, 2019, 573, 225-229


8. Heng zhou#, Feng Luo#, Zhipu Luo#, Dan Li, Cong Liu*, Xueming Li*, Programming conventional electron microscopes for solving ultrahigh-resolution structures of small and macro-molecules, Analytical Chemistry, 2019, 91, 10996-11003


9. Meijing Li#, Xian Xia#, Yuanyuan Tian#, Qi Jia#, Xiaoyu Liu#, Ying Lu, Ming Li*, Xueming Li*, and Zhucheng Chen*, Mechanism of DNA translocation underlying chromatin remodeling by Snf2, Nature, 2019, 567, 409-413


10. Mingxu Hu#, Hongkun Yu#, Kai Gu#, Zhao Wang, Huabin Ruan, Kunpeng Wang, Siyuan Ren, Bing Li, Lin Gan, Shizhen Xu, Guangwen Yang*, Yuan Shen*, Xueming Li*, A particle-filter framework for robust cryoEM 3D reconstruction, Nature Methods, 2018, 15, 1083-1089


11. Meng Yin#, Zhaofeng Yan#, Xueming Li*, Structural insight into the assembly of the Type II Secretion System Pilotin-Secretin Complex from enterotoxigenic Escherichia coli, Nature Microbiology, 2018, 3,581-587.


12. Qiancheng Zhao#, Heng Zhou#, Shaopeng Chi#, Yanfeng Wang#, Jianhua Wang, Jie Geng, Kun Wu, Wenhao Liu, Tingxin Zhang, Meng-Qiu Dong, Jiawei Wang, Xueming Li*, Bailong Xiao*. Structure and mechanogating mechanism of the Piezo1 channel. Nature, 2018, 554, 487-492.


13. Minghui Li#, Xiaoyuan Zhou#, Shu Wang, Ye Gong, Deyuan Su, Huan Li, Xueming Li*, and Jian Yang*, Structure of a eukaryotic cyclic nucleotide-gated channel, Nature, 2017, 542, 60-65.


14. Xiaoyu Liu#, Meijing Li#, Xian Xia#, Xueming Li*, and Zhucheng Chen*, Mechanism of chromatin remodeling revealed by the Snf2-nucleosome structure, Nature, 2017, 544, 440-445.


15. Feng Wang#, Huichao Gong#, Gaochao Liu,# Meijing Li , Chuangye Yan, Tian Xia*, Xueming Li*, Jianyang Zeng*, DeepPicker: a Deep Learning Approach for Fully Automated Particle Picking in Cryo-EM, Journal of Structural Biology, 2016(195), 325-336


16. Xueming Li, Paul Mooney, Shawn Zheng, Chris Booth, Michael B. Braunfeld, Sander Gubbens, David A. Agard* and Yifan Cheng*, Electron counting and beam-induced motion correction enable near atomic resolution single particle cryoEM, Nature Methods, 10, 584-590, 2013.