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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蛋白手性变体新型标志物,初步绘制多种人类疾病与蛋白质手性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。


Full Publication List:

AT NANKAI UNIVERSITY: (Since 2021)

2025

61Jun Liu, Xiaoli Wang, Xiangjun Si, Rui Zhao, Weida Qin, and Gongyu Li*. Time-resolved In-cell Protein Interactions and Structural Dynamics via Rapid Buffer Online Exchange-Ion Mobility-Mass Spectrometry. Angew. Chem. Int. Ed. 2025, DOI: 10.1002/anie.202518076. 

60Zihao Qiao, Fanshu Cao, Ming Chen, Qiyan Zhong, Jun Liu, Gongyu Li, and Zhenbo Mo*. Isolation and Reactivity of a silylene-stabilized Borasilylidene. J. Am. Chem. Soc. 2025, 147, 49, 44708-44713.   

59Xiaoli Wang, Ning Wang, Peng Zhou, Ruochen Guo, Na Song, Zeyu Zhang, Xuehai Yan,* Zhilin Yu,* and Gongyu Li*Oligomerization Propensity Governs Self-Assembly Morphology: In-sights from Steady-State Oligomer Analysis. Anal. Chem. 2025, 97, 40, 21863–21872 

58Weida Qin, Ruomeng Li, Juan Liu, Jun Liu, Xiaoli Wang, Binbin Hu, Zhen Zheng, Zhilin Yu and Gongyu Li*Spatially Constrained Disulfide Bond Shuffling Delays Insulin Aggregation and Enhances Neurotoxicity. Nat. Commun. 2025, 16, 6841. 

57Juan Liu, Gongyu Li*Advancing Peptide and Protein Stereoisomer Analysis with Conformation-based Chiral Separation via Liquid Chromatography and Ion Mobility-Mass Spectrometry. Anal. Sens. 2025, e202400115. [Invited Review

56Xiaoli Wang, Tingting Liang, Anran Jin, Chenao Zhang, Jiaxin Zhou, Mingrui Li, Ziyi Sun and Gongyu Li*C-terminal Radical Oxidation Inhibits α-Synuclein Aggregation and Cytotoxicity Via an Oxidative Oligomer-disrupting Pathway. J. Am. Chem. Soc. 2025, 147, 26, 23136-23144. 

55Juan Kong, An-An Liu, Xia Xu, Bo Tang, Yan-Yan Chen, Wei Zhao, Jianhong Jia, Ling-Ling Yang, Gongyu Li, and Dai-Wen Pang*. Making Cells as a "Nirvana Phoenix": Precise Coupling of Precursors Prior to ROS Bursts for Intracellular Synthesis of Quantum Dots. J. Am. Chem. Soc. 2025, 147, 18, 15645-15653. 

54Na Jiang, Hekun Yang, Yi Lei, Weida Qin, Huifang Xiong, Kuan Chen, Kunrong Mei, Gongyu Li, Xin Mu,* and Ruibing Chen*. Characterization of dsRNA binding proteins through solubility analysis identifies ZNF385A as a dsRNA homeostasis regulator. Nat. Commun. 2025, 16, 3433. 

53Xia Xu, Weida Qin, Haohao Fu, Ruomeng Li, Chunxiao Chen, Baofa Sun, Daiwen Pang, Xueguang Shao and Gongyu Li*High-Coverage Stereoproteome Mapping Uncovers Pervasive Protein Stereoisomerization Associated with NeurodegenerationAnal. Chem. 2025, 97, 14, 7814-7824. [全球第一篇手性蛋白组学研究论文][Supplementary Cover

52Yamei Wang,+ Dongbei Jin,+ Lifang Ren, Ning Wang, Yifei Jia, Zhen Zheng, Wensheng Cai, Haohao Fu* and Gongyu Li*Sialylation Shields Glycoproteins from Oxidative Stress: Mechanistic Insights into Sialic Acid Oxidation and Structural StabilityJ. Am. Chem. Soc.  2025, 147, 7, 5828-5838. [+, co-first authors]

51Hongxia Zhang,+ Ming Ji,Yamei Wang,Mengmeng Jiang, Zongyu Lv, Gongyu Li,* Lulu Wang*, and Zhen Zheng*. Intrinsic PD-L1 Degradation Induced by a Novel Self-Assembling Hexapeptide for Enhanced Cancer Immunotherapy. Adv. Sci.  2025, 12, 2410145. [+, co-first authors]

50. Di Zhang, Jinjun Gao, Zhijun Zhu, Qianying Mao, Zhiqiang Xu, Pankaj K. Singh, Cornelius C. Rimayi, Carlos Moreno-Yruela, Shuling Xu, Gongyu Li, Yi-Cheng Sin, Yue Chen, Christian A. Olsen, Nathaniel W. Snyder, Lunzhi Dai,* Lingjun Li* and Yingming Zhao*. Lysine l-lactylation is the dominant lactylation isomer induced by glycolysis. Nat. Chem. Biol. 2025, 21, 91-99.   

2024

49. Chao-Rui Ma, Guan-Wang Huang, Hui Xu, Zhan-Lin Wang, Zheng-Hao Li, Jun Liu, Yin Yang, Gongyu Li, Yanfeng Dang*, and Fei Wang*. Site-selective arene C–H amination with iron-aminyl radical. Nat. Cat. 2024, 7, 636-645.   

48Binbin Hu, Weida Qin, Yushi Wang, Zeyu Zhang, Ninglin Chen, Hongbo Wang, Gongyu Li, Yang Shi*, and Zhilin Yu*. Assembly-Glued Ligands and Warheads for Hypoxia-Activatable Supramolecular Covalent Inhibitors. Adv. Funct. Mater.  2024, 34, 52, 2411179.

47Feng Tian, Ruo-Chen Guo, Chunxia Wu, Xin Liu, Zeyu Zhang, Yamei Wang, Hao Wang, Gongyu Li, and Zhilin Yu*.  Assembly of Glycopeptides in Living Cells Resembling Viral Infection for Cargo DeliveryAngew. Chem. Int. Ed. 2024, e202404703.

46Xia Xu, Weida Qin, Ruomeng Li, Qianqian Wang, Ning Liu, and Gongyu Li*. Mass Spectrometry-based Deep Coverage Proteome: Evaluation of Cellular Protein Extraction MethodsChem. J. Chin. Univ. 2024, 45(11), 20240344.


45Yifei Jia,+ Yichang Liu,+ Yamei Wang,+ Jinyu Li* and Gongyu Li*. Sialylation-Induced Stabilization of Dynamic Glycoprotein Conformations Unveiled by Time-Aligned Parallel Unfolding and Glycan Releasing Mass Spectrometry. Chem. Sci. 2024, 15, 14431-14439. [AIU: Glycoprotein Sialylation.] [+, co-first authors]


44Hongxia Zhang, Mengmeng Jiang, Weiyu Xing, Rui Zhao, Gongyu Li, and Zhen Zheng*. Peptide-IR820 Conjugate: A Promising Strategy for Efficient Vascular Disruption and Hypoxia Induction in MelanomaACS Appl. Mater. Interfaces 2024, 16, 31, 40641-40652. 

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 CRM197Chin. Chem. Lett. 2025, 110401. [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, e202312837.

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.