
李惠琳
教授
研究领域:(1)开发及利用整合结构质谱技术(包括native top-down MS, HDX-MS, cross-linking MS等)研究蛋白质机器(蛋白-药物、蛋白-蛋白、蛋白-DNA等)的结构和功能;
(2)开发middle-down/top-down蛋白质组学技术探索蛋白翻译后修饰(PTMs)在生命过程中的调控机制。
办公电话: 广州市广州大学城外环东路132号中山大学
联系邮箱: lihlin6@mail.sysu.edu.cn
Contact Information:
group website: https://m.x-mol.com/groups/li_huilin?lang=en
Email:lihlin6@mail.sysu.edu.cn
Address:广州市广州大学城外环东路132号bm11222宝马娱乐网站421室
Brief Introduction
李惠琳,博士,中山大学教授,博导。2017年12月通过“中山大学百人计划”进入bm11222宝马娱乐网站工作。长期从事生物质谱研究,围绕完整蛋白的直接测序及修饰位点定位、蛋白-药物作用机制及蛋白非共价复合物的结构解析等科学难题开发质Top-Down MS谱新方法,以实现对蛋白复合物结构及药物作用机制的深度探索。其研究成果发表在Nature Chemistry, Analytical Chemistry, J. Am. Soc. Mass Spectrom.等国际主流化学、分析及质谱类杂志。
Research Direction
(1)整合结构质谱技术(Integrative Structural Mass Spectrometry)的开发及其在药物作用分子机制、靶向药物筛选及蛋白复合物结构分析中的应用:
- Native top-down MS:直接建立蛋白/蛋白复合物的序列、结构和功能之间的关联关系
- 氢氘交换质谱(HDX-MS):获取配体结合位点及蛋白结构动态变化等信息
- 交联质谱(cross-linking MS):开发新型交联剂的开发,用以研究蛋白结构及蛋白-蛋白相互作用研究
- 表面标记质谱(surface labeling MS):获取蛋白结构及蛋白-蛋白相互作用信息
(2)Middle-down/top-down蛋白质组学技术探索蛋白翻译后修饰(PTMs)在生命过程中的调控机制:
- Middle-down蛋白组学新技术的开发:酶切方法及组学流程的优化
- 应用Middle-down蛋白组学技术探索PTMs在生命体中的调控机制
- Intact蛋白分析及Top-down MS测序
Education
2009年10月至2012年12月:博士,英国华威大学化学系,导师:Peter B. O’Connor 教授;
2005年9月至2008年12月:硕士,中国科学院长春应用化学研究所,导师:刘志强 研究员;
1998年9月至2002年7月:学士,山东大学bm11222宝马娱乐网站
Work Experience
2017年12月-至今 教授,博士生导师,中山大学,bm11222宝马娱乐网站
2016年9月至2017年9月:博士后,法国遗传与分子细胞生物学研究所结构生物学系,合作导师:Bruno Kieffer & Marc-Andre Delsuc教授;
2013年1月至2016年1月:博士后,美国加州大学洛杉矶分校David Geffen医学院生物化学系,合作导师:Joseph Loo教授;
2002年7月至2009年9月:研习员,助理研究员,中国科学院长春应用化学研究所
Grants
国家自然科学基金面上项目,基于质谱新技术的I型组蛋白去乙酰酶抑制剂的作用机制研究 ,2019.1-2022.12,项目负责人
国家自然科学基金重大研究计划培养项目,多位点蛋白修饰检测的middle-down组学质谱分析新方法,2020.1-202.12, 项目负责人
中山大学“百人计划二期”启动项目,项目负责人
广东省自然科学基金面上项目,2019.10-2022.09,项目负责人
中山大学重大项目培育和新兴、交叉学科资助项目,2019.1-2020.12,项目负责人
Awards
- “珠江人才计划”青年拔尖人才(2019)
- AOMSC Young Scientist Travel Award (亚洲与太平洋会议青年科学家旅行奖,2017)
- ASMS Postdoctoral Career Development Award ( 美国质谱学会博士后职业发展奖,2014)
- 2009-2012 Warwick Postgraduate Research Scholarship (WPRS) (2009-2012)
- University of Warwick Departmental Studentships (2009-2012)
- Travel Award for the 25th Lake Louise Tandem Mass Spectrometry Workshop (2012)
- IMSF Travel Grant for the 19th International Mass Spectrometry Conference (2012)
- BMSS Travel Award for the 59th ASMS Conference on Mass Spectrometry (2011)
- Travel Award for the 8th Uppsala Conference on Electron Capture and Transfer Dissociation (2011)
Publications
Y Luo, H Li*. Structure-Based Inhibitor Discovery of Class I Histone Deacetylases (HDACs). Int. J. Mol. Sci. 2020, Just accepted.
- Z Yin*, J Huang, H Miao, O Hu, H Li*. High-Pressure Electrospray Ionization Yields Supercharged Protein Complexes from Native Solutions While Preserving Noncovalent Interactions. Anal. Chem. 2020, 92, 18, 12312–12321.
- Y Ying, H Li*. Recent progress in the analysis of protein deamidation using mass spectrometry.Methods, 2020, in press, https://doi.org/10.1016/j.ymeth.2020.06.009
- 黄静,李惠琳*. 氢氘交换质谱技术在蛋白质和蛋白复合物结构研究中的应用进展。分析测试学报,2020,39(1). 10.3969/j.issn.1004-4957.2020.01.008
- I Campuzano*, M Nshanian, C Spahr, C Lantz, C Netirojjanakul, H Li, P Wongkongkathep, J Wolff, J Loo*. High Mass Analysis with a Fourier Transform Ion Cyclotron Resonance Mass Spectrometer: From Inorganic Salt Clusters to Antibody Conjugates and Beyond. J. Am. Soc. Mass Spectrom. 2020, 31, 5, 1155–1162
- S Cleary, H Li, D Bagal, J Loo, I Campuzano, J Prell. Extracting Charge and Mass Information from Highly Congested Mass Spectra Using Fourier-Domain Harmonics. J. Am. Soc. Mass Spectrom. 2018, 29, 10, 2067–2080
- H Li*. Native top-down proteomics comes into light. Sci. China Life Sci. 2018, 61(11), 1425–1427.
- H Li*, HH Nguyen, RRO Loo, I Campuzano, JA Loo*. An integrated native mass spectrometry and top-down proteomics method that connects sequence to structure and function of macromolecular complexes. Nat. Chem. 2018, 10(2):139-148
- H Li*, Y Sheng, W McGee, M Cammarata, D Holden, JA Loo*. Structural Characterization of Native Proteins and Protein Complexes by Electron Ionization Dissociation. Anal. Chem. 2017. 89, 2731-2738
- I Campuzano, H Li, G Svitel, D Bagal, L Jia, R Kurzeja, H Xu, JA Loo*. Bacteriorhodopsin and Nanodisc Analysis by Orthogonal Acceleration Time-of-flight, Ion Cyclotron Resonance and OrbiTrap Analyzers. Anal. Chem. 2016. 88, 12427-12436.
- P Wongkongkathep, H Li, X Zhang, RRO Loo, R Julian and JA Loo*. Enhancing Disulfide Bond Cleavage by UV Excitation and Electron Capture Dissociation for Top-Down Mass Spectrometry. Int. J. Mass Spectrom. 2015. 390, 137-145.
- X Zhang, H Li, JA Loo, RR Julian*, B Moore, P Wongkongkathep, RRO Loo. Radical directed dissociation of peptides and proteins by IRMPD and SORI-CID with FTICR mass spectrometry. Rapid Commun. Mass Spectrom. 2014. 28, 2729-2734.
- H Li, P Wongkongkathep, SL Van Orden, RRO Loo, JA Loo*. Revealing Ligand Binding Sites and Quantifying Subunit Variants of Non-Covalent Bound Protein Complexes in a Single Native Top-Down FTICR MS Experiment. J. Am. Soc. Mass Spectrom. 2014. 25, 2060-2068.
- H Li, JJ Wolff, SL Van Orden, JA Loo*. Native Top-Down ESI-MS of 158 kDa Protein Complex by High Resolution Fourier Transform Ion Cyclotron Resonance Mass Spectrometry. Anal. Chem. 2014, 86, 317-320 (Paper On the Cover)
- H Li, JR Snelling, MP Barrow, JH Scrivens, PJ Sadler, PB O’Connor*. Mass Spectrometric Strategies to Improve the Identification of Pt(II)-modification Sites on Peptides and proteins. J. Am. Soc. Mass Spectrom. 2014. 25, 1217-1227.
- Y Zhao, NJ Farrer, H Li, JS Butler, RJ McQuitty, A Habtemariam, F Wang, PJ Sadler*. De novo generation of singlet oxygen and ammine ligands by photoactivation of a platinum anticancer complex. Angew. Chem. 2013. 52, 1-6.
- Y Qi, H Li, RH Wills, P Perez-Hurtado, X Yu, DPA Kilgour, MP Barrow, C Lin, PB O’Connor*. Absorption-mode Fourier transform mass spectrometry: The effects of apodization and phasing on modified protein spectra. J. Am. Soc. Mass Spectrom. 2013, 24, 828-834.
- J Wei, H Li, MP Barrow, PB O’Connor*. Structural Characterization of Chlorophyll a by High Resolution Tandem Mass Spectrometry. J. Am. Soc. Mass Spectrom. 2013. 24, 753-760.
- Y Qi, Z Liu, H Li, PJ Sadler, PB O'Connor*. Mapping the Protein-Binding Sites for Novel Iridium(III) Anticancer Complexes Using Electron Capture Dissociation. Rapid Commun. Mass Spectrom. 2013, 27, 2028-2032.
- Y Zhao, JA Woods, NJ Farrer, KS Robinson, J Pracharova, J Kasparkova, O Novakova, H Li, L Salassa, AM Pizarro, GJ Clarkson, L Song, V Brabec, PJ Sadler*. Diazido mixed-amine platinum(IV) anticancer complexes activatable by visible-light form novel DNA adducts. Chem. Eur. J. 2013, 19, 9578-9591.
- H Li, PB O’Connor*. Electron Capture Dissociation of Disulfide, Sulfur-Selenium, and Diselenide Bound Peptides. J. Am. Soc. Mass Spectrom. 2012, 23, 2001-2010.
- H Li#, SA Wells#, JE Jimenez-Roldan, RA Römer, Y Zhao, PJ Sadler, PB O’Connor*. Protein Flexibility is Key to Cisplatin Cross-linking in Calmodulin. Prot. Sci. 2012. 21, 1269-1279.
- Y Qi, MP Barrow, H Li, JE Meier, SL Van Orden, CJ Thompson, PB O'Connor*. Absorption-mode: The Next Generation of Fourier Transform Mass Spectra. Anal. Chem. 2012. 84, 2923–2929.
- H Zhou, H Li, Z Zheng, F Song, J Xing, Z Liu*, S Liu*. Screening for α-Glucosidase Inhibitors from Coptidis-rehmanniae Herb Couple by Using Ultrafiltration Liquid Chromatography/Mass Spectrometry. J. Liq. Chrom. Rel. Technol. 2012, 35, 1-14.
- H Li, TY Lin, SL Van Orden, Y Zhao, MP Barrow, AM Pizarro, Y Qi, PJ Sadler, PB O'Connor*. Use of Top-down and Bottom-up Fourier Transform Ion Cyclotron Resonance Mass Spectrometry for Mapping Calmodulin Sites Modified by Platinum Anticancer Drugs. Anal. Chem. 2011, 83, 9507-9515.
- H Li, Y Zhao, HIA Phillips, Y Qi, TY Lin, PJ Sadler, PB O’Connor*. Mass Spectrometry Evidence for Cisplatin as a Protein Cross-linking Reagent. Anal. Chem. 2011, 83, 5369-5376.
- Y Qi, MP Barrow, SL Van Orden, CJ Thompson, H Li, P Perez-Hurtado, PB O'Connor*. Variation of the Fourier Transform Mass Spectra Phase Function with Experimental Parameters. Anal. Chem. 2011, 83, 8477-8483.
- W Liu, S Liu, H Li, F Song, Z Liu, S Liu*. Binding of Alpha 1-acid Glycoprotein with Aconitum Alkaloids: An Investigation by IF-MALDI-FT-MS. Rapid Commun. Mass Spectrom. 2011, 25, 973-978.
- S Liu, J Yan, H Li, F Song, Z Liu, Z Liu, S Liu. Studies on Chemical Constituents of Compound Indigowoad Root Granule by Mass Spectrometry. Chem. J. Chinese U. 2010, 31, 1137-1142.
- H Li, F Song, J Xing, Z Liu*, S Liu*. Screening and Structures Characterization of α-Glucosidase Inhibitors from Hawthorn Leaves Flavonoids Extract by Ultrafiltration LC-DAD-MSn and SORI-CID FT ICR MS. J. Am. Soc. Mass Spectrom. 2009, 20, 1496-1503.
- X Meng, H Li, F Song, C Liu, Z Liu, S Liu. Studies on Triterpenoids and Flavones in Glycyrrhiza uralensis Fisch. by HPLC-ESI-MSn and FT-ICR-MSn. Chinese J. Chem. 2009, 27, 299-305.
- H Li, F Song, Z Zheng, Z Liu*, S Liu*. Characterization of Oligsaccharides and Phenolid Acids in the Chinese Herb Tanshen by ESI-FT ICR MS. J. Mass Spectrom. 2008, 43, 1545-1552.
- H Yue, Z Pi, H Li, F Song, Z Liu, S Liu. Studies on the Stability of Diester-diterpenoid Alkaloids from the Genus Aconitum L. by High Performance Liquid Chromatography Combined with Electrospray Ionisation Tandem Mass Spectrometry (HPLC/ESI/MSn). Phytochem. Anal. 2008, 19, 141-147.
- Y Liu, Z Liu, H Li, F Song, S Liu. Studies on Diterpenoids Constituents from Euphorbia Kansui by Electrospray Ionization Multi-Stage Tandem Mass Spectrometry. Chem. J. Chinese U. 2008, 29, 1727-1735.
- X Qiu, M Cui, H Li, Z Liu, S Liu. Prompt Disulfide Fragmentations of Disulfide-containing Proteins in a Matrix-Assisted Laser Desorption/ Ionization Source. Rapid Commun. Mass Spectrom. 2007, 21, 3520-3525.
- Y Zhao, F Song, H Yue, X Guo, H Li, Z Liu, S Liu. Deoxyaconitine of Metabolite of Aconitine by Human Intestinal Bacteria and Electrospray Ionization Tandem Mass Spectrometry. Chem. J. Chinese U. 2007, 28, 2051-2055.
- H Dong, Z Liu, F Song, Z Yu, H Li, S Liu. Structural Analysis of Monoterpene Glycosides Extracted from Paeonia lactiflora Pall. Using Electrospray Ionization Fourier Transform Ion Cyclotron Resonance Mass Spectrometry and High-performance Liquid Chromatography/ Electrospray Ionization Tandem Mass Spectrometry. Rapid Commun. Mass Spectrom. 2007, 21, 3193-3199.
- S Wang, H Li, Z Liu, S Liu, B Cui. Studies on the Contents of Catechin and Epicatechin in Catechu by HPLC, Lishizhen Medicine and Materia Medica Research. 2006, 17, 490-491.
- H Dong, Z Liu, F Song, Z Yu, H Li, S Liu. Studies on Paeoniflorin by Electrospray Ionization Tandem Mass Spectrometry. Chem. J. Chinese U. 2006, 27, 2066-2069.
- H Li, J Xing, Z Liu, S Liu. Analysis of Cephalosporins by Electrospray Ionization Multi-Stage Tandem Mass Spectrometry. J. Chinese Mass Spec. Soc. 2005, 26, 198-202.
其他
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