研究方向
谢晓亮,生物物理化学家,现任昌平实验室主任、北京大学理学部主任,是改革开放后第一位获得哈佛大学终身教授和冠名讲席教授的大陆学者,并于2018年全职回到母校北京大学工作。其研究工作显著提升了胚胎植入前遗传学检测的精准度,由此诞生了首例“MALBAC婴儿”,迄今已有超过一万名新生儿通过该技术成功避免了父母携带的致病基因突变。新冠疫情期间,其团队运用单细胞基因组学技术筛选出高效抗SARS-CoV-2抗体,但该抗体随后的奥密克戎变异株出现而失效。这促使他们进一步研制出迄今仍保持广谱中和活性的抗体SA55,该抗体已挽救数千生命,且目前仍保持未被病毒逃逸的记录。谢晓亮是中国科学院院士,美国国家科学院、国家医学院、艺术与科学学院三院外籍院士,曾获多项国际重要奖项,主要包括美国阿尔伯尼生物医学奖、美国化学会彼得·德拜物理化学奖及北京市中关村奖。
代表性论文
Single Cell Genomics
1. Wu, H.; Zhang, J.; Tan, L.; Xie, X. Single-cell Micro-C profiles 3D genome structures at high resolution and characterizes multi-enhancer hubs. Nat Genet. 2025, 57, 1777–1786. 10.1038/s41588-025-02247-6
2. He, R.; Dong, W.; Wang, Z.; Xie, C.; Gao, L.; Ma, W.; Shen, K.; Li, D.; Pang, Y.; Jian, F.; Zhang, J.; Yuan, Y.; Wang, X.; Zhang, Z.; Zhen, Y.; Liu, S.; Luo, C.; Chai, X.; Ren, J.; Zhu, Z.; Xie, X. Genome-wide single-cell and single-molecule footprinting of transcription factors with deaminase. PNAS. 2024, 121(52), e2423270121. 10.1073/pnas.242327012
3. Chapman, A.; Lee, D.; Cai, W.; Ma, W.; Li, X.; Sun, W.; Xie, X. Correlated gene modules uncovered by high-precision single-cell transcriptomics. PNAS. 2022, 119(51), e2206938119. 10.1073/pnas.2206938119
4. Tan, L.; Ma, W.; Wu, H.; Sun, W.; Zheng, Y.; Xing, D.; Chen, R.; Li, X.; Daley, N.; Deisseroth, K.; Xie, X. Changes in genome architecture and transcriptional dynamics progress independently of sensory experience during post-natal brain development. Cell. 2021, 184(3), 741-758. 10.1016/j.cell.2020.12.032
5. Tan, L.; Xing, D.; Chang, C.; Li, H.; Xie, X. Three-dimensional genome structures of single diploid human cells. Science. 2018, 361, 924-928. 10.1126/science.aat5641
6. Chen, C.; Xing, D.; Tan, L.; Li, H.; Zhou, G.; Huang, L.; Xie, X. Single-cell whole-genome analyses by Linear Amplification via Transposon Insertion (LIANTI). Science. 2017, 356, 189-194. 10.1126/science.aak9787
7. Yan, L.; Huang, L.; Xu, L.; Huang, J.; Ma, F.; Zhu, X.; Tang, Y.; Liu, M.; Lian, Y.; Liu, P.; Li, R.; Lu, S.; Tang, F.; Qiao, J.; Xie, X. Live births after simultaneous avoidance of monogenic diseases and chromosome abnormality by next-generation sequencing with linkage analyses. Proc Natl Acad Sci USA. 2015, 112(52), 15964-15969. 10.1073/pnas.1523297113
8. Hou, Y.; Fan, W.; Yan, L.; Li, R.; Lian, Y.; Huang, J.; Li, J.; Xu, L.; Tang, F.; Xie, X.; Qiao, J. Genome Analyses of Single Human Oocytes. Cell. 2013, 155(7), 1492-1506. 10.1016/j.cell.2013.11.040
9. Ni, X.; Zhuo, M.; Su, Z.; Duan, J.; Gao, Y.; Wang, Z.; Zong, C.; Bai, H.; Chapman, A.; Zhao, J.; Xu, L.; An, T.; Ma, Q.; Wang, Y.; Wu, M.; Sun, Y.; Wang, S.; Li, Z.; Yang, X.; Yong, J.; Su, X.; Lu, Y.; Bai, F.; Xie, X.; Wang, J. Reproducible copy number variation patterns among single circulating tumor cells of lung cancer patients. Proceedings of the National Academy of Sciences. 2013, 110(52), 21083-21088. 10.1073/pnas.1320659110
10. Zong, C.; Lu, S.; Chapman, A.; Xie, X. Genome-Wide Detection of Single-Nucleotide and Copy-Number Variations of a Single Human Cell. Science. 2012, 338(6114), 1622-1626. 10.1126/science.1229164
11. Lu, S.; Zong, C.; Fan, W.; Yang, M.; Li, J.; Chapman, A.; Zhu, P.; Hu, X.; Xu, L.; Yan, L.; Bai, F.; Qiao, J.; Tang, F.; Li, R.; Xie, X. Probing Meiotic Recombination and Aneuploidy of Single Sperm Cells by Whole-Genome Sequencing. Science. 2012, 338(6114), 1627-1630. 10.1126/science.1229112
12. Shiroguchi, K.; Jia, T.; Sims, P.; Xie, X. Digital RNA sequencing minimizes sequence-dependent bias and amplification noise with optimized single-molecule barcodes. Proceedings of the National Academy of Sciences. 2012, 109(4), 1347-1352. 10.1073/pnas.1118018109
13. Sims, P.; Greenleaf, W.; Duan, H.; Xie, X. Fluorogenic DNA sequencing in PDMS microreactors. Nat Meth. 2011, 8(7), 575-580. 10.1038/nmeth.1629
Coherent Raman Microscopy
1. Ji, M.; Orringer, D.; Freudiger, C.; Ramkissoon, S.; Liu, X.; Lau, D.; Golby, A.; Norton, I.; Hayashi, M.; Agar, N.; Young, G.; Spino, C.; Santagata, S.; Camelo-Piragua, S.; Ligon, K.; Sagher, O.; Xie, X. Rapid, Label-Free Detection of Brain Tumors with Stimulated Raman Scattering Microscopy. Science Translational Medicine. 2013, 5(201), 201ra119-201ra119. 10.1126/scitranslmed.3005954
2. Wang, M.; Min, W.; Freudiger, C.; Ruvkun, G.; Xie, X. RNAi screening for fat regulatory genes with SRS microscopy. Nat Meth. 2011, 8(2), 135-138. 10.1038/nmeth.1556
3. Saar, B.; Freudiger, C.; Reichman, J.; Stanley, C.; Holtom, G.; Xie, X. Video-Rate Molecular Imaging in Vivo with Stimulated Raman Scattering. Science. 2010, 330(6009), 1368-1370. 10.1126/science.1197236
4. Freudiger, C.; Min, W.; Saar, B.; Lu, S.; Holtom, G.; He, C.; Tsai, J.; Kang, J.; Xie, X. Label-Free Biomedical Imaging with High Sensitivity by Stimulated Raman Scattering Microscopy. Science. 2008, 322(5909), 1857-1861. 10.1126/science.1165758
5. Evans, C.; Potma, E.; Puoris'haag, M.; Cote, D.; Lin, C.; Xie, X. Chemical imaging of tissue in vivo with video-rate coherent anti-Stokes Raman scattering microscopy. Proceedings of the National Academy of Sciences. 2005, 102(46), 16807-16812. 10.1073/pnas.0508282102
6. Zumbusch, A.; Holtom, C.; Xie, X. Three-Dimensional Vibrational Imaging by Coherent Anti-Stokes Raman Scattering. Physical Review Letters. 1999, 82, 4142-4145.
Gene Expression and Regulation - Live Cell Single Molecule Studies
1. Taniguchi, Y.; Choi, P.; Li, G.; Chen, H.; Babu, M.; Hearn, J.; Emili, A.; Xie, X. Quantifying E. coli Proteome and Transcriptome with Single-Molecule Sensitivity in Single Cells. Science. 2010, 329(5991), 533-538. 10.1126/science.1188308
2. Choi, P.; Cai, L.; Frieda, K.; Xie, X. A Stochastic Single-Molecule Event Triggers Phenotype Switching of a Bacterial Cell. Science. 2008, 322(5900), 442-446. 10.1126/science.1161427
3. Elf, J.; Li, G.; Xie, X. Probing Transcription Factor Dynamics at the Single-Molecule Level in a Living Cell. Science. 2007, 316(5828), 1191-1194. 10.1126/science.1141967
4. Yu, J.; Xiao, J.; Lao, K.; Xie, X. Probing Gene Expression in Live Cells, One Protein Molecule at a Time. Science. 2006, 311(5767), 1600-1603. 10.1126/science.1119623
5. Cai, L.; Friedman, N.; Xie, X. Stochastic protein expression in individual cells at the single molecule level. Nature. 2006, 440(7082), 358-362. 10.1038/nature04599
Single Molecule Enzymology
1. Chong, S.; Chen, C.; Ge, H.; Xie, X. Mechanism of Transcriptional Bursting in Bacteria. Cell. 2014, 158(2), 314-326. 10.1016/j.cell.2014.05.038
2. Kim, S.; Brostromer, E.; Xing, D.; Jin, J.; Chong, S.; Ge, H.; Wang, S.; Gu, C.; Yang, L.; Gao, Y.; Su, X.; Sun, Y.; Xie, X. Probing Allostery Through DNA. Science. 2013, 339(6121), 816-819. 10.1126/science.1229223
3. English, B.; Min, W.; van Oijen, A.; Lee, K.; Luo, G.; Sun, H.; Cherayil, B.; Kou, S.; Xie, X. Ever-fluctuating single enzyme molecules: Michaelis-Menten equation revisited. Nat Chem Biol. 2006, 2(2), 87-94. 10.1038/nchembio759
4. Yang, H.; Luo, G.; Karnchanaphanurach, P.; Louie, T.; Rech, I.; Cova, S.; Xun, L.; Xie, X. Protein Conformational Dynamics Probed by Single-Molecule Electron Transfer. Science. 2003, 302(5643), 262-266. 10.1126/science.1086911
5. Lu, H.; Xun, L.; Xie, X. Single Molecule Enzymatic Dynamics. Science. 1998, 282, 1877.
Single Molecule Spectroscopy and Imaging
1. Chong, S.; Min, W.; Xie, X. Ground-State Depletion Microscopy: Detection Sensitivity of Single-Molecule Optical Absorption at Room Temperature. The Journal of Physical Chemistry Letters. 2010, 1(23), 3316-3322. 10.1021/jz1014289
2. Min, W.; Lu, S.; Chong, S.; Roy, R.; Holtom, G.; Xie, X. Imaging chromophores with undetectable fluorescence by stimulated emission microscopy. Nature. 2009, 461(7267), 1105-1109. 10.1038/nature08438
3. Sánchez, E.; Novotny, L.; Xie, X. Near-field Fluorescence Microscopy Based on Two-Photon Excitation With Metal Tips. Phys. Rev. Lett. 1999, 82, 4014.
4. Lu, H.; Xie, X. Single-Molecule Spectral Fluctuations at Room Temperature. Nature. 1997, 385, 143.
5. Sánchez, E.; Novotny, L.; Holtom, G.; Xie, X. Room-Temperature Fluorescence Imaging and Spectroscopy of Single Molecules by Two-Photon Excitation. J. Phys. Chem. A. 1997, 101, 7019.
6. Xie, X.; Dunn, R. Probing Single Molecule Dynamics. Science. 1994, 265, 361.
COVID-19
1. Cao, Y.; Jian, F.; Wang, J.; Yu, Y.; Song, W.; Yisimayi, A.; Wang, J.; An, R.; Chen, X.; Zhang, N.; Wang, Y.; Wang, P.; Zhao, L.; Sun, H.; Yu, L.; Yang, S.; Xiao, T.; Gu, Q.; Shao, F.; Hao, X.; Xu, Y.; Jin, R.; Shen, Z.; Wang, Y.; Xie, X. Imprinted SARS-CoV-2 humoral immunity induces convergent Omicron RBD evolution. Nature. 2023, 614, 521-529. 10.1038/s41586-022-05644-7
2. Cao, Y.; Jian, F.; Zhang, Z.; Yisimayi, A.; Hao, X.; Bao, L.; Yuan, F.; Yu, Y.; Du, S.; Wang, J.; Xiao, T.; Song, W.; Zhang, Y.; Liu, P.; An, R.; Wang, P.; Wang, Y.; Yang, S.; Niu, X.; Zhang, Y.; Gu, Q.; Shao, F.; Hu, Y.; Yin, W.; Zheng, A.; Wang, Y.; Qin, C.; Jin, R.; Xiao, J.; Xie, X. Rational identification of potent and broad sarbecovirus-neutralizing antibody cocktails from SARS convalescents. Cell Reports. 2022, 41(12), 111845. 10.1016/j.celrep.2022.111845
3. Cao, Y.; Song, W.; Wang, L.; Liu, P.; Yue, C.; Jian, F.; Yu, Y.; Wang, Y.; Yisimayi, A.; Wang, P.; Wang, Y.; Zhu, Q.; Deng, J.; Fu, W.; Yu, L.; Zhang, N.; Wang, J.; Xiao, T.; An, R.; Wang, J.; Liu, L.; Yang, S.; Niu, X.; Gu, Q.; Shao, F.; Hao, X.; Meng, B.; Gupta, R.; Jin, R.; Wang, Y.; Xie, X.; Wang, X. Characterization of the enhanced infectivity and antibody evasion of Omicron BA.2.75. Cell Host & Microbe. 2022, 30(11), 1527-1539. 10.1016/j.chom.2022.09.018
4. Cao, Y.; Yisimayi, A.; Jian, F.; Song, W.; Xiao, T.; Wang, L.; Du, S.; Wang, J.; Wang, J.; Li, Q.; Chen, X.; Yu, Y.; Wang, P.; Zhang, Z.; Liu, P.; An, R.; Hao, X.; Wang, Y.; Wang, J.; Feng, R.; Sun, H.; Zhao, L.; Zhang, W.; Zhao, D.; Zheng, J.; Yu, L.; Li, C.; Zhang, N.; Wang, R.; Niu, X.; Yang, S.; Song, X.; Chai, Y.; He, Y.; Shi, Y.; Zheng, L.; Li, Z.; Gu, Q.; Shao, F.; Huang, W.; Jin, R.; Shen, Z.; Wang, Y.; Wang, X.; Xiao, J.; Xie, X. BA.2.12.1, BA.4 and BA.5 escape antibodies elicited by Omicron infection. Nature. 2022, 608, 593-602. 10.1038/s41586-022-04980-y
5. Cao, Y.; Wang, J.; Jian, F.; Xiao, T.; Song, W.; Yasimayi, A.; Huang, W.; Li, Q.; Wang, P.; An, R.; Wang, J.; Wang, Y.; Niu, X.; Yang, S.; Liang, H.; Sun, H.; Li, T.; Yu, Y.; Cui, Q.; Liu, S.; Yang, X.; Du, S.; Zhang, Z.; Hao, X.; Shao, F.; Jin, R.; Wang, X.; Xiao, J.; Wang, Y.; Xie, X. Omicron escapes the majority of existing SARS-CoV-2 neutralizing antibodies. Nature. 2021, 602, 657-663. 10.1038/s41586-021-04385-3
6. Cao, Y.; Yisimayi, A.; Bai, Y.; Huang, W.; Li, X.; Zhang, Z.; Yuan, T.; An, R.; Wang, J.; Xiao, T.; Du, S.; Ma, W.; Song, L.; Li, Y.; Li, X.; Song, W.; Wu, J.; Liu, S.; Li, X.; Zhang, Y.; Su, B.; Guo, X.; Wei, Y.; Gao, C.; Zhang, N.; Zhang, Y.; Dou, Y.; Xu, X.; Shi, R.; Lu, B.; Jin, R.; Ma, Y.; Qin, C.; Wang, Y.; Feng, Y.; Xiao, J.; Xie, X. Humoral immune response to circulating SARS-CoV-2 variants elicited by inactivated and RBD-subunit vaccines. Cell Research. 2021, 31(7), 732-741. 10.1038/s41422-021-00514-9
7. Du, S.; Cao, Y.; Zhu, Q.; Yu, P.; Qi, F.; Wang, G.; Du, X.; Bao, L.; Deng, W.; Zhu, H.; Liu, J.; Nie, J.; Zheng, Y.; Liang, H.; Liu, R.; Gong, S.; Liu, J.; Xu, H.; Yisimayi, A.; Lv, Q.; Wang, B.; He, R.; Han, Y.; Zhao, W.; Bai, Y.; Qu, Y.; Gao, X.; Ji, C.; Wang, Q.; Gao, N.; Huang, W.; Wang, Y.; Xie, X.; Su, X.; Xiao, J.; Qin, C. Structurally resolved SARS-CoV-2 antibody shows high efficacy in severely infected hamsters and provides a potent cocktail pairing strategy. Cell. 2020, 183(4), 1013-1023.e13. 10.1016/j.cell.2020.09.035
8. Cao, Y.; Su, B.; Guo, X.; Sun, W.; Deng, Y.; Bao, L.; Zhu, Q.; Zhang, X.; Zheng, Y.; Geng, C.; Chai, X.; He, R.; Li, X.; Lv, Q.; Zhu, H.; Deng, W.; Xu, Y.; Wang, Y.; Qiao, L.; Tan, Y.; Song, L.; Wang, G.; Du, X.; Gao, N.; Liu, J.; Xiao, J.; Su, X.; Du, Z.; Feng, Y.; Qin, C.; Qin, C.; Jin, R.; Xie, X. Potent Neutralizing Antibodies against SARS-CoV-2 Identified by High-Throughput Single-Cell Sequencing of Convalescent Patients' B Cells. Cell. 2020, 182(1), 73-84.e16. 10.1016/j.cell.2020.05.025