谢晓亮( 二 )


谢晓亮课题组的研究方向包含基础科学研究领域、技术研究领域和医学研究领域三个领域 。基础研究:单分子酶学、单分子生物物理化学、基因表达和调控、表观遗传学、细胞分化和重编程机理、基因组不稳定性 。技术发展:单分子成像、单细胞基因组学、相干拉曼散射显微成像、DNA 测序 。医学研究:体外受精胚胎植入前遗传学筛查与诊断、早期癌症诊断 。学术贡献
谢晓亮是单分子酶学的创始人、单分子生物物理化学的奠基人之一、相干拉曼散射显微成像技术和单细胞基因组学的开拓者 。谢晓亮教授作为单分子生物物理化学家,他勇于突破学科界限,从物理化学、生物物理到生物化学,再到分子生物学、基因组学及临床医学,无畏探索,不断创新,在相关新兴交叉学科做出了创造性贡献 。

谢晓亮

文章插图
世界上第一例MALBAC婴儿诞生 (2014年9月19日)谢晓亮不仅是生物物理化学基础科学研究的国际领军人物,近年来大力推动了无标记光学成像技术和新型单细胞基因组测序技术在医学中的套用 。2012年谢晓亮在单细胞全基因组学研究有了突破性进展,开发了单细胞全基因组均匀扩增的新方法—多重退火循环扩增法(MALBAC) 。2014年9月19日,世界上第一例“MALBAC婴儿”在北医三院诞生,标誌着中国胚胎植入前遗传诊断技术处于世界领先水平 。迄今为止,谢晓亮团队利用MALBAC技术为中国三百多个患有单基因遗传病的家庭成功避免了疾病的子代传递,为数千位孕妇避免了染色体异常胚胎的移植,减少了流产和唐氏综合徵等染色体异常疾病的发生 。谢晓亮曾获得美国物理化学领域最高的奖项“Peter Debye”奖、美国生物物理学会的最高得奖项“Founders”奖和美国医学领域最高的奖项之一Albany医学奖;2017年9月,谢晓亮教授获得“求是杰出科学家奖”,以表彰他在国内单分子生物学和精準医疗领域的卓越成就 。2017年11月,谢晓亮教授当选为中国科学院外籍院士,这是继当选美国国家科学院院士、美国国家医学院院士和美国艺术与科学学院院士后,斩获的第四顶院士桂冠 。代表论文
截至2017年4月,谢晓亮教授共发表SCI收录科学论文210余篇 。Single Molecule Spectroscopy and ImagingXie, X. Sunney; Dunn, Robert C. "Probing Single Molecule Dynamics" Science 265: 361-364 (1994).Sánchez, Erik J; Novotny, Lukas; Xie, X. Sunney. "Near-field Fluorescence Microscopy Based on Two-photon Excitation with Metal Tips" Phys Rev Lett 82: 4014-4017 (1999). Min, Wei; Lu, Sijia; Chong, Shasha; Roy, Rahul; Holtom, Gary R.; Xie, X. Sunney. "Imaging Chromophores with Undetectable Fluorescence by Stimulated Emission Microscopy" Nature 461: 1105-1109 (2009).Chong, Shasha; Min, Wei; Xie, X. Sunney. "Ground-State Depletion Microscopy: Detection Sensitivity of Single-Molecule Optical Absorption at Room Temperature" J Phys Chem Lett 1:3316-3322 (2010).Zhou, Yuexin; Wang, Ping; Tang, Feng; Gao, Ge; Huang, Lei; Wei, Wensheng; Xie, X. Sunney “Painting a specific chromosome with CRISPR/Cas9 for live-cell imaging”, Cell Research, doi:10.1038/cr.2017.9 (2017).Single Molecule EnzymologyLu, H. Peter; Xun, Luying; Xie, X. Sunney. "Single-Molecule Enzymatic Dynamics" Science 282: 1877-1882 (1998).Yang, Haw; Luo, Guobin; Karnchanaphanurach, Pallop; Louie, Tai-Man; Rech, Ivan; Cova, Sergio; Xun, Luying; Xie, X. Sunney. "Protein Conformational Dynamics Probed by Single-Molecule Electron Transfer" Science 302: 262-266 (2003).Min, Wei; Luo, Guobin; Cherayil, Binny J.; Kou, S. C.; Xie, X. Sunney. "Observation of a Power-Law Memory Kernel for Fluctuations within a Single Protein Molecule" Phys Rev Lett 94: 198302(1-4) (2005).English, Brian P.; Min, Wei; van Oijen, Antoine M.; Lee, Kang Taek; Luo, Guobin; Sun, Hongye; Cherayil, Binny J.; Kou, S.C.; Xie, X. Sunney. "Ever-Fluctuating Single Enzyme Molecules: Michaelis-Menten Equation Revisited" Nat Chem Bio 2: 87-94 (2006). Blainey, Paul C.; Luo, Guobin; Ko9u, S.C.; Mangel, Walter F.; Verdine, Gregory L.; Bagchi, Biman; Xie, X. Sunney. "Nonspecifically Bound Proteins Spin While Diffusing Along DNA" Nat Struct Mol Biol 16: 1224-1229 (2009).Kim, Sangjin; Brostr?mer, Erik, Xing, Dong; Jin, Jianshi; Chong, Shasha; Ge, Hao, Wang, Siyuan; Gu, Chan; Yang, Lijiang; Gao, Yiqin; Su, Xiao-dong; Sun, Yujie; Xie, X. Sunney. “Probing Allostery Through DNA” Science 339: 816-819 (2013).Chong, Shasha; Chen, Chongyi; Ge, Hao; Xie, X. Sunney. "Mechanism of Transcriptional Bursting in Bacteria" Cell 158: 314-326 (2014).Gene Expression and RegulationYu, Ji; Xiao, Jie; Ren, Xiaojia; Lao, Kaiqin; Xie, X. Sunney. "Probing Gene Expression in Live Cells, One Protein Molecule at a Time" Science 311: 1600-1603 (2006).Cai, Long; Friedman, Nir; Xie, X. Sunney. "Stochastic Protein Expression in Individual Cells at the Single Molecule Level" Nature 440: 358-362 (2006).Elf, Johan; Li, Gene-Wei; Xie, X. Sunney. "Probing Transcription Factor Dynamics at the Single-Molecule Level in a Living Cell" Science 316: 1191-1194 (2007).Choi, Paul J.; Cai, Long; Frieda, Kirsten; Xie, X. Sunney. "A Stochastic Single-Molecule Event Triggers Phenotype Switching of a Bacterial Cell" Science 322: 442-446 (2008).Taniguchi, Yuichi; Choi, Paul J.; Li, Gene-Wei; Chen, Huiyi; Babu, Mohan; Hearn, Jeremy; Emili, Andrew; Xie, X. Sunney. "Quantifying E. coli Proteome and Transcriptome with Single-Molecule Sensitivity in Single Cells" Science 329: 533-538 (2010). Chong, Shasha; Chen, Chongyi; Ge, Hao; Xie, X. Sunney. "Mechanism of Transcriptional Bursting in Bacteria" Cell 158: 314-326 (2014).Ge, Hao; Qian, Hong; and Xie, X. Sunney. "Stochastic Phenotype Transition of a Single Cell in an Intermediate Region of Gene State Switching" Phys Rev Lett 114(7) (2015).Coherent Raman MicroscopyZumbusch, Andreas; Holtom, Gary R.; Xie, X. Sunney. “Vibrational Microscopy Using Coherent Anti-Stokes Raman Scattering" Phys Rev Lett 82: 4142-4145 (1999).Evans, Conor L.; Potma, Eric O.; Puoris'haag, Mehron; C?té, Daniel; Lin, Charles P.; Xie, X. Sunney. "Chemical imaging of tissue in vivo with video-rate coherent anti-Stokes Raman scattering microscopy" Proc Nat. Aca Sci 102: 16807-16812 (2005).Freudiger, Christian W.; Min, Wei; Saar, Brian G.; Lu, Sijia; Holtom, Gary R.; He, Chengwei; Tsai, Jason C.; Kang, Jing X.; Xie, X. Sunney. "Label-Free Biomedical Imaging with High sensitivity by Stimulated Raman Scattering Microscopy" Science 322:1857-1860 (2008).Saar, Brian G.; Freudiger, Christian W.; Reichman, Jay; Stanley, C. Michael; Holtom, Gary R.; Xie, X. Sunney. "Video-Rate Molecular Imaging in Vivo with Stimulated Raman Scattering" Science 330: 1368-1370 (2010).Wang, Meng C.; Min, Wei; Freudiger, Christian W.; Ruvkun, Gary; Xie, X. Sunney. "RNAi Screening for Fat Regulatory Genes with SRS Microscopy" Nat Methods 8: 135-138 (2011). Fu, Dan; Zhou, Jing; Zhu, Wenjing Suzanne; Manley, Paul W.; Wang, Y. Karen; Hood, Tami; Wylie, Andrew; Xie, X. Sunney. "Imaging the Intracellular Distribution of Tyrosine Kinase Inhibitors in Living Cells with Quantitative Hyperspectral Stimulated Raman Scattering" Nat Chem 6: 614-622 (2014).Single Cell GenomicsZong, Chenghang; Lu, Sijia; Chapman, Alec R.; Xie, X. Sunney. "Genome-Wide Detection of Single-Nucleotide and Copy-Number Variations of a Single Human Cell" Science 338: 1622-1626 (2012).Lu, Sijia; Zong, Chenghang; Fan, Wei; Yang, Mingyu; Li, Jinsen; Chapman, Alec R.; Zhu, Ping; Hu, Xuesong; Xu, Liya; Bai, Fan; Qiao, Jie; Tang, Fuchou; Li, Ruiqiang; Xie, X. Sunney. "Probing Meiotic Recombination and Aneuploidy of Single Sperm Cells by Whole-Genome Sequencing" Science 338: 1627-1630 (2012).Hou, Yu; Fan, Wei; Yan, Liying; Li, Rong; Lian, Ying; Huang, Jin; Li, Jinsen; Xu, Liya; Tang, Fuchou; Xie, X. Sunney; Qiao, Jie. "Genome Analyses of Single Human Oocytes" Cell 155: 1492-1506 (2013).Yan, Liying; Huang, Lei; Xu, Liya; Huang, Jin; Ma, Fei; Zhu, Xiaohui; Tang, Yaqiong; Liu, Mingshan; Lian, Ying; Liu, Ping; Li, Rong; Lu, Sijia; Tang, Fuchou; Qiao, Jie; Xie, X Sunney "Live Births after Simultaneous Avoidance of Monogenic Diseases and Chromosome Abnormality by Next-generation Sequencing with Linkage Analyses," Proc Natl Acad Sci USA, 112(52), 15964-15969, (2015). Chen, Chongyi; Xing, Dong; Tan, Longzhi; Li, Heng; Zhou, Guangyu; Huang, Lei; Xie, X. Sunney "Single-cell whole-genome analyses by Linear Amplification via Transposon Insertion (LIANTI)," Science 356, 189-194 (2017).Key Review ArticlesMin, Wei; Freudiger, Christian W.; Lu, Sijia; Xie, X. Sunney. "Coherent Nonlinear Optical Imaging: beyond Fluorescence Microscopy" Annu. Rev. Phys. Chem. 62: 507-530 (2011).Li, Gene-Wei; Xie, X. Sunney. "Central Dogma at the Single-Molecule Level in Living Cells" Nature 475: 308-315 (2011).Xie, X. Sunney. "Enzyme Kinetics, Past and Present" Science 342: 1457-1459 (2013).Xie, X. Sunney. "Single Molecules Meet Genomics: Pinpointing Precision Medicine" JAMA 20: 2021-2 (2015).Huang Lei; Ma Fei; Chapman Alec; Lu Sijia; Xie X. Sunney. “Single-Cell Whole-Genome Amplification and Sequencing” Annu. Rev. Genomics Hum. Genet. 16: 79-102 (2015).Cheng, Ji-xin; Xie, X. Sunney. “Vibrational Spectroscopic Imaging of Living Systems: An Emerging Platform for Biology and Medicine” Science 350, aaa8870 (2015).人才培养