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成果及论文

学术成绩 (Academic Impact):

针对“人类疾病关联蛋白变体的规模化发现及其构效精准解析”这一关键科学问题,李功玉课题组依托非变性离子淌度质谱平台,开发系列跨尺度手性差异放大新策略,打破传统质谱无法鉴定分子量不变型翻译后修饰的技术壁垒,成功搭建《高性能构象分辨质谱》多场景分析系统,规模化发现神经疾病和肺腺癌肿瘤的新型潜在蛋白标志物,初步绘制多种人类疾病与蛋白立体异构变体的分子关联图谱,有望应用于病理机制解析、早期分子分型、个性化预后诊疗及精准靶标发现等方向。

李功玉课题组《高性能构象分辨质谱》相关成果被 Nat. Commun. 与 F1000Prime 等网站选为亮点文章,主页置顶报道;主持承担国家重点研发计划、国家高层次青年人才计划与天津市重点项目等多项国家省部级科研项目;以通讯和第一作者发表论文20余篇(含Angew. Chem. Int. Ed.Nat. Commun.Anal. Chem.Chem. Sci.Nano Today 等);2022年与2023年连续获评南开大学化学学院《科研新锐奖》;2023年,获天津市科学技术协会“先进学会工作者”称号;2019年获美国质谱协会博士后职业发展奖;2019年入围美国分析化学及光谱协会年度创新奖决赛;担任天津市色谱研究会理事、天津市药理学会临床多组学专业委员会委员;担任 《Chinese Chemical Letters》《Frontiers in Chemistry》《Journal of Analysis and Testing》《分析测试学报》等杂志青年编委。


2021年至今代表作 (Top Papers Since 2021):

TP1. Angew. Chem. 2023, 14578[D蛋白与肿瘤]

TP2. Nano Today 2024, 102122[多肽自组装]

TP3. Chem. Sci. 2023, 5936[D蛋白与AD]

TP4. Anal. Chem. 2024, 2292[构象分辨质谱]

TP5. Anal. Chem. 2023, 10895[D蛋白与免疫]

TP6. Anal. Chem. 2023, 2221[构象分辨质谱]

TP7. Anal. Chem. 2022, 2142[构象分辨质谱]

TP8. Anal. Chem. 2022, 3774[构象分辨质谱]


Full Publication List:

AT NANKAI UNIVERSITY: (Since 2021)

2024

43Xia Xu, Guiqian Yang, Zhen Zheng, Cody J. Wenthur, Jinyu Li* and Gongyu Li*. The sheet-to-helix transition is a potential gas-phase unfolding pathway for a multidomain protein CRM197. Chin. Chem. Lett. 2024, acccepted. [First CIU Pathway.]


42. Jun Liu, Zhen Zheng, Ning-Wang and Gongyu Li*. Plasma-Droplet Fusion-Mass Spectrometry Reveals Sub-Millisecond Protein Unfolding Dynamics Induced by Reactive Oxygen SpeciesAnal. Chem. 2024, 96, 6, 2292-2296. [ROS-induced Protein Unfolding.]



41Hongxia Zhang, Liyuan Peng, Weida Qin, Deying Jia, Rui Zhao, Mengmeng Jiang, Ming Ji, Lulu Wang, and Gongyu Li*, and Zhen Zheng*. Enhanced Chemotherapy and Anti-Metastasis with In Situ Nanosphere-to-Nanofiber TransitionNano Today 2024, 54, 102122. [CRMS: Peptide Self-assembly.]


2023

40贾-翼菲,王雅梅,李功玉*.蛋白质糖基化修饰的非变性构象分辨质谱研究进展[J]. 中国药科大学学报 2023, 54(6):674-681. [专辑约稿.]

39Ruochen Guo, Ning Wang, Weishu Wang, Zeyu Zhang, Wendi Luo, Yushi Wang, Haiqin Du, Yifei Xu, Gongyu Li* and Zhilin Yu*. Artificial Peptide-Protein Necrosomes Promote Cell DeathAngew. Chem. Int. Ed. 2023, e202314578. [STEP: Cancer Biomarker.]

38Ming Chen, Zhaoyin Zhang, Jun Liu, Gongyu Li, Lili Zhao and Zhenbo Mo*. Isolation and Reactivity of Homoleptic Diphosphene Lead Complexes. Angew. Chem. Int. Ed. 2023, doi: 10.1002/anie.202312837.

37Jun Liu, Yamei Wang, Xiaoli Wang, Weida Qin and Gongyu Li*. Measuring Protein Unfolding Thermodynamic Stability in One Minute with Digital Temperature Control-equipped nanoESI-Mass SpectrometryInt. J. Mass Spectrom. 2023, 494, 117151. [DTC: rapid structural probing.] [Invited for Special Issue]

36Rui Zhao, Ning Liu, Zhen Zheng, and Gongyu Li*. Enhanced Stability Differentiation of Therapeutic Polyclonal Antibodies with All Ion Unfolding-Ion Mobility-Mass SpectrometryJ. Am. Soc. Mass Spectrom. 2023, 34, 10, 2289-2295.  [AIU: polyclonal antibody.] 

35Zhen Zheng, Min Ma, Yifei Jia, Yusi Cui, Rui Zhao, Shuangshuang Li, Cody Wenthur*, Lingjun Li* and Gongyu Li*. Expedited Evaluation of Conformational Stability-Heterogeneity Associations for Crude Polyclonal Antibodies in Response to Conjugate VaccinesAnal. Chem. 2023, 95, 29, 10895-10902. (*, co-corresponding[AIU: conjugate vaccine.] 

34Gongyu Li*Chae Kyung Jeon, Min Ma, Yifei Jia, Zhen Zheng, Daniel G. Delafield, Gaoyuan Lu, Elena V. Romanova, Jonathan V. Sweedler, Brandon Ruotolo* and Lingjun Li*. Site-specific Chirality-conferred Structural Compaction Differentially Mediates the Cytotoxicity of Aβ42. Chem. Sci. 2023, 14, 5936-5944. (*, co-corresponding[STEP: AD Biomarker.]

33. Xia Xu, Li Han, Zhen Zheng*, Rui Zhao, Lingjun Li, Xueguang Shao and Gongyu Li*Composite Multidimensional Ion Mobility-Mass Spectrometry for Improved Differentiation of Stereochemical Modifications. Anal. Chem. 2023, 95, 4, 2221–2228. (*, co-corresponding[CRMS: Differential Amplification.] 


2022

32. 许霞,张晨傲,孙梓懿,郑珍,李功玉*非变性结构质谱在蛋白提取、离子源开发与构象解析方面的研究进展质谱学报 2022, 43, 6, 740-753
质谱学报非变性质谱研究与应用专辑约稿 ][2021-2023年度优秀论文]

31. 许霞,朱致君,李灵军*,李功玉*蛋白立体化学修饰的离子淌度质谱研究进展质谱学报 2022, 43, 5, 580-595。
质谱学报离子淌度质谱技术研究及应用》专辑约稿。蛋白手性修饰STEP》的第一篇系统性中文综述. ]

30Ashley Phetsanthad, Gongyu Li*, Chae Kyung Jeon, Brandon T. Ruotolo and Lingjun Li*Comparing Selected-Ion Collision Induced Unfolding (CIU) with All Ion Unfolding (AIU) Methods for Comprehensive Protein Conformational Characterization. J. Am. Soc. Mass Spectrom. 2022, 33, 6, 944–951. (*, co-corresponding[CRMS: AIU.]

29. Yuan Liu, Gongyu Li*, Tingjia Gu, and Lingjun Li*Nanosecond Photochemical Reaction (nsPCR) for Enhanced Identification, Quantification and Visualization of Primary Amine-containing Metabolites by MALDI-Mass Spectrometry. AnalChem. 2022, 94, 9, 3774-3781. (*, co-corresponding)

28Gongyu Li*, Ashley Phetsanthad, Min Ma, Qinying Yu, Ashita Nair, Zhen Zheng, Kellen DeLaney, Fengfei Ma, Seungpyo Hong, Lingjun Li*Native ion mobility-mass spectrometry-enabled fast structural interrogation of labile protein surface modifications at the intact protein level. Anal. Chem. 2022, 94, 4, 2142-2153. (*, co-corresponding[CRMS: AIU.]

27Gongyu Li, Yuan Liu and Lingjun Li*. Nanosecond Photochemical Reaction (nsPCR) for Enhanced Mass Spectrometric Identification, Quantification, and Visualization of Metabolites and NeuropeptidesMethods Mol. Biol. 2022, 2437, 143-157. (book chapter, doi: 10.1007/978-1-0716-2030-4_10)


2021

26Gongyu LiJunfeng Huang, Zhen Zheng, Qinjingwen Cao, Yuwei Tian, Guangming Huang, Lingjun Li and Brandon Ruotolo*. Bicarbonate Buffers Can Promote Crosslinking and Alternative Gas-phase Dissociation Pathways for Multiprotein Complexes. Int. J. Mass Spectrom.  2021, 469, 116687. [Invited for Special Issue]



PRIOR TO NANKAI UNIVERSITY: (Through 2020)

25. Yang Liu, Gongyu Li and Lingjun Li*. Targeted Top-Down Mass Spectrometry for the Characterization and Tissue-Specific Functional Discovery of Crustacean Hyperglycemic Hormones (CHH) and CHH Precursor-Related Peptides in Response to Low pH Stress. J. Am. Soc. Mass Spectrom. 2021, 32, 6, 1352-1360.

24. Hua Zhang, Xudong Shi, Nhu Q. Vu, Gongyu Li, Zihui Li, Yatao Shi, Miyang Li, Bin Wang, Nathan V. Welham, Manish S. Patankar, and Lingjun Li*. On-tissue derivatization for matrix-assisted laser desorption/ionization mass spectrometry imaging of N-glycans in cancer tissues. Anal. Chem. 2020, 92, 19, 13361–13368.

23. Gaoyuan Lu, Xiaowei Xu, Gongyu Li, Nian Wang, Yinxue Zhu, Ning Wan, Yatao Shi, Lingjun Li, Haiping Hao*, and Hui Ye*. Sub-residue Resolution Footprinting of Ligand-Protein Interactions by Carbene Chemistry and Ion Mobility-Mass Spectrometry. Anal. Chem. 2020, 92, 947-956.

22Gongyu Li, Daniel Delafield, and Lingjun Li*. Improved Structural Elucidation of Peptide Isomers and Their Receptors Using Advanced Ion Mobility-Mass Spectrometry. Trends Anal. Chem. 2020, 124, 115546.
[Invited Review.]

21Gongyu Li, Fengfei Ma, Qinjingwen Cao, Zhen Zheng, Kellen DeLaney, Rui Liu and Lingjun Li*. Nanosecond Photochemically Promoted Click Chemistry for Enhanced Neuropeptide Visualization and Rapid Protein Labeling. Nat. Commun. 2019, 10, 4697.
[F1000Prime Recommendation: being of SPECIAL SIGNIFICANCE in its field.]
[FEATURED in Nature Communications Editors’ HIGHLIGHTS.]
[Behind the Paper: Mass Spectrometry Fuels Nanosecond Photochemistry]
[Rapid SMS: nsPCR.]

20Gongyu Li, Kellen DeLaney, and Lingjun Li*. Molecular Basis for Chirality-regulated Aβ Self-Assembly and Receptor Recognition. Nat. Commun. 2019, 10, 5038.
[High-resolution SMS.]

19. Qinjingwen Cao, Yijia Wang, Bingming Chen, Fengfei Ma, Ling Hao, Gongyu Li, Chuanzi Ouyang, and Lingjun Li*. Visualization and Identification of Neurotransmitters in Crustacean Brain via Multifaceted Mass Spectrometric Approaches. ACS Chem. Neurosci. 2019, 10, 1222-1229.

18Gongyu Li, Qinjingwen Cao, Yang Liu, Kellen DeLaney, Zichuan Tian, Eugene Moskovets and Lingjun Li*. Characterizing and Alleviating Ion Suppression Effects in Atmospheric Pressure Matrix-Assisted Laser Desorption/Ionization (AP-MALDI). Rapid Commun. Mass Spectrom. 2019, 33, 327-335.

17. Yuting Chen‡, Gongyu Li‡, Siming Yuan, Yang Pan, Yangzhong Liu and Guangming Huang*. Ultrafast Micro-Electrophoresis: Behind Direct Mass Spectrometry Measurement for Proteins and Metabolites in Living Cell/Cells. Anal. Chem. 2019, 91, 10441-10447. (‡, co-first author)

16. Shihui Zheng, Siming Yuan, Zhuanghao Hou, Gongyu Li, Yuting Chen, Yang Pan, Yangzhong Liu and Guangming Huang*. Charge-dependent modulation of specific and nonspecific protein-metal ion interactions in nanoelectrospray ionization mass spectrometry. Rapid Commun. Mass Spectrom. 2019, 33, 1502.

15. Tiantian Fang, Wanbiao Chen, Yaping Sheng, Siming Yuan, Qiaowei Tang, Gongyu Li, Guangming Huang, Jihu Su, Xuan Zhang,* Jianye Zang,* and Yangzhong Liu*. Tetrathiomolybdate Induces Dimerization of the Metal-binding Domain of ATPase and Inhibits Platination of the Protein. Nat. Commun. 2019, 10, 186.

14Gongyu Li‡, Shihui Zheng‡, Yuting Chen, Zhuanghao Hou and Guangming Huang*. Reliable Tracking In-solution Protein Unfolding via Ultrafast Thermal Unfolding/Ion Mobility-Mass Spectrometry. Anal. Chem. 2018, 90, 7997-8001. (‡, co-first author)
[Rapid SMS: Online IM-MS of ms Solution Unfolding .]

13Gongyu Li‡, Siming Yuan‡, Shihui Zheng, Yangzhong Liu* and Guangming Huang*. In Situ Living Cell Protein Analysis by Single-step Mass Spectrometry. Anal. Chem. 2018, 90, 3409-3415. (‡, co-first author)
[Ultrafast MS: Workflow.]

12Gongyu Li‡, Siming Yuan‡, Shihui Zheng, Yuting Chen, Zhen Zheng, Yangzhong Liu* and Guangming Huang*. The effect of salts in promoting specific and competitive interactions between zinc finger proteins and metals. J. Am. Soc. Mass Spectrom. 2017, 28, 2658-2664. (‡, co-first author)

11. Zhen Zheng‡, Peiyao Chen‡, Gongyu Li‡, Yunxia Zhu‡, Zhonghua Shi, Yufeng Luo, Chun Zhao, Ziyi Fu, Xianwei Cui, Chenbo Ji, Fuqiang Wang,* Guangming Huang* and Gaolin Liang*. Mechanistic study of CBT-Cys click reaction and its application for identifying bioactive N-terminal cysteine peptides in amniotic fluid. Chem. Sci. 2017, 8, 214-222. (‡, co-first author)

10. Zhen Zheng, Gongyu Li, Chengfan Wu, Miaomiao Zhang, Yue Zhao, and Gaolin Liang*. Intracellular synthesis of D-aminoluciferin for bioluminescence generation. Chem. Commun. 2017, 53, 3567-3570.

9Gongyu Li, Siming Yuan, Yang Pan, Yangzhong Liu and Guangming Huang*. Binding states of protein-metal complexes in cells. Anal. Chem. 2016, 88, 10860-10866.
[Ultrafast MS: Mechanism + Application.]

8. Yue Yin, Gongyu Li, Yafeng Guan and Guangming Huang*. Sheathless interface to match flow rate of capillary electrophoresis with electrospray mass spectrometry using regular-sized capillary. Rapid Commun. Mass Spectrom. 2016, 30 Suppl 1, 68-72.

7. Zhen Zheng, Hongbin Sun, Chen Hu, Gongyu Li, Xiaomei Liu, Peiyao Chen, Yusi Cui, Jing Liu, Junfeng Wang, and Gaolin Liang*. Using "On/Off" FNMR/MRI signals to sense tyrosine kinase/phosphatase activity in vitro and in cell lysates. Anal. Chem. 2016, 88, 3363-3368.

6. Zhen Zheng, Lin Wang, Wei Tang, Peiyao Chen, Hui Zhu, Yue Yuan, Gongyu Li, Huafeng Zhang, Gaolin Liang*. Hydrazide D-luciferin for in vitro selective detection and intratumoral imaging of Cu2+. Biosens. Bioelectron. 2016, 83, 200-204.

5Gongyu Li, Jiying Pei, Yue Yin and Guangming Huang*. Direct sequencing of a disulfide-linked peptide with electrospray ionization tandem mass spectrometry. Analyst 2015, 140, 2623-2627.

4Gongyu Li and Guangming Huang*. Alleviation of ion suppression effect in sonic spray ionization with induced alternating current voltage. J. Mass Spectrom. 2014, 49, 639-645.

3Gongyu Li, Yue Yin, Guangming Huang*. Increased disulfide peptide sequence coverage via “cleavage ON/OFF” switch during nanoelectrospray. RSC Adv. 2014, 4, 59650-59654.

2. Hongying Zhu, Gongyu Li, Guangming Huang*. Screening of complicated matrixes with paper assisted ultrasonic spray ionization mass spectrometry. J. Am. Soc. Mass Spectrom. 2014, 25, 935-942.

1. Fugang Xu*, Miao Deng, Gongyu Li, Shouhui Chen, Li Wang*. Electrochemical behavior of cuprous oxide-reduced graphene oxide nanocomposites and their application in nonenzymatic hydrogen peroxide sensing. Electrochim. Acta 2013, 88, 59-65.