基于核磁共振技术的蛋白质-蛋白质和蛋白质-小分子相互作用研究。

招收攻读博士和或硕士学位的研究生（含推免生），应试学生应具备生物或化学专业知识背景，有志于从事蛋白质-配体相互作用研究。欢迎有兴趣的同学与我直接联系。

张乃霞博士1998年毕业于北京医科大学（现为北京大学医学部），获理学学士学位。2003年毕业于中国科学院上海有机化学研究所，获有机化学博士学位。2004年以博士后身份赴美国明尼苏达大学留学，2008年获聘为明尼苏达大学研究助理教授，2010年10月加入中国科学院上海药物研究所工作至今，现任中国科学院上海药物研究所研究员、所级公共技术中心核磁技术服务部首席技术专家、课题组长、博士生导师。兼任中国生物物理学会生物磁共振分会委员、中国科学院磁共振技术联盟常务理事以及中国蛋白质结构数据库科学顾问委员会委员。张乃霞博士长期致力于基于NMR技术的蛋白质-蛋白质、蛋白质-小分子相互作用研究，主持建立了基于核磁共振技术的蛋白质-蛋白质相互作用研究平台、基于核磁共振技术的蛋白质-活性化合物相互作用研究平台、以及基于核磁共振代谢组学技术的药效学、药理学和毒理学研究平台。

2010-10~现在, 中国科学院上海药物研究所, 研究员
2008-06~2010-02,美国明尼苏达大学, 研究助理教授
2004-05~2008-05,美国明尼苏达大学, 博士后
2003-07~2004-05,中国科学院上海有机化学研究所, 临时聘用科研人员

2023-09-24-今,中国蛋白质结构数据库科学顾问委员会, 委员
2021-05-13-今,Magnetic Resonance Letters, 编委
2019-06-12-今,中国科学院磁共振技术联盟, 常务理事
2019-06-01-今,中国生物物理学会生物磁共振分会, 委员
2014-08-13-今,Scientific Reports, 编委

   

（1） Human Aha1's N-terminal extension confers it holdase activity in vitro, PROTEIN SCIENCE, 2023, 
（2） Sodium Oligomannate Electrostatically Binds to A�� and Blocks Its Aggregation, JOURNAL OF PHYSICAL CHEMISTRY B, 2023, 第 11 作者
（3） Dipyridamole interacts with the N-terminal domain of HSP90 and antagonizes the function of the chaperone in multiple cancer cell lines, BIOCHEMICAL PHARMACOLOGY, 2023, 第 11 作者
（4） Pharmacological characterization of the small molecule 03A10 as an inhibitor of ��-synuclein aggregation for Parkinson's disease treatment, Acta Pharmacologica Sinica, 2023, 第 11 作者
（5） Structure-based discovery of potent USP28 inhibitors derived from Vismodegib, EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, 2023, 第 11 作者
（6） Otilonium Bromide acts as a selective USP28 inhibitor and exhibits cytotoxic activity against multiple human cancer cell lines, BIOCHEMICAL PHARMACOLOGY, 2023, 
（7） Ribonucleotide reductase holoenzyme inhibitor COH29 interacts with deubiquitinase ubiquitin-specific protease 2 and downregulates its substrate protein cyclin D1, FASEB JOURNAL, 2022, 第 11 作者
（8） High-Throughput-Methyl-Reading (HTMR) assay: a solution based on nucleotide methyl-binding proteins enables large-scale screening for DNA/RNA methyltransferases and demethylases, NUCLEIC ACIDS RESEARCH, 2022, 第 12 作者
（9） Targeting the RT loop of Src SH3 in Platelets Prevents Thrombosis without Compromising Hemostasis, ADVANCED SCIENCE, 2022, 第 14 作者
（10） Pharmacokinetics-based identification of pseudoaldosterogenic compounds originating from Glycyrrhiza uralensis roots(Gancao)after dosing LianhuaQingwen capsule, Pharmacokinetics-based identification of pseudoaldosterogenic compounds originating from Glycyrrhiza uralensis roots (Gancao) after dosing LianhuaQingwen capsule, ACTA PHARMACOLOGICA SINICA, 2021, 第 17 作者
（11） 5-Aminonaphthalene derivatives as selective nonnucleoside nuclear receptor binding SET domain-protein 2 (NSD2) inhibitors for the treatment of multiple myeloma, EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, 2021, 第 15 作者
（12） Protective Effects of 28-O-Cafeoyl Betulin (B-CA) on the Cerebral Cortex of Ischemic Rats Revealed by a NMR-Based Metabolomics Analysis (vol 89, pg 631, 2020), NEUROCHEMICAL RESEARCH, 2021, 第 11 作者
（13） Expression, purification and characterization of the second DUSP domain of deubiquitinase USP20/VDU2, PROTEIN EXPRESSION AND PURIFICATION, 2021, 第 11 作者
（14） Applications of Solution NMR in Drug Discovery, MOLECULES, 2021, 第 11 作者
（15） USP28 and USP25 are downregulated by Vismodegib in vitro and in colorectal cancer cell lines, FEBS JOURNAL, 2021, 第 11 作者
（16） Aha1 Exhibits Distinctive Dynamics Behavior and Chaperone-Like Activity, MOLECULES, 2021, 第 11 作者
（17） Natural product 1,2,3,4,6-penta-O-galloyl-beta-D-glucopyranose is a reversible inhibitor of glyceraldehyde 3-phosphate dehydrogenase, ACTA PHARMACOLOGICA SINICA, 2021, 第 12 作者
（18） Protective Effects of 28-O-Caffeoyl Betulin (B-CA) on the Cerebral Cortex of Ischemic Rats Revealed by a NMR-Based Metabolomics Analysis, NEUROCHEMICAL RESEARCH, 2021, 第 11 作者
（19） Suppression of asparagine synthetase enhances the antitumor potency of ART and artemalogue SOMCL-14-221 in non-small cell lung cancer, CANCER LETTERS, 2020, 第 11 作者
（20） Covalent Inhibitors Allosterically Block the Activation of Rho Family Proteins and Suppress Cancer Cell Invasion, ADVANCED SCIENCE, 2020, 第 19 作者
（21） Allosteric Regulation of Hsp90 alpha's Activity by Small Molecules Targeting the Middle Domain of the Chaperone, ISCIENCE, 2020, 第 11 作者
（22） Allosteric Regulation of Hsp90�����s Activity by Small Molecules Targeting the Middle Domain of the Chaperone, ISCIENCE, 2020, 第 14 作者
（23） A Small-Molecule Inhibitor Targeting TRIP13 Suppresses Multiple Myeloma Progression, CANCERRESEARCH, 2020, 第 20 作者
（24） Exploration of Fragment Binding Poses Leading to Efficient Discovery of Highly Potent and Orally Effective Inhibitors of FABP4 for Anti-inflammation, JOURNAL OF MEDICINAL CHEMISTRY, 2020, 第 8 作者
（25） Design, synthesis, and biological evaluation of tetrahydroquinolin derivatives as potent inhibitors of CBP bromodomain, BIOORGANIC CHEMISTRY, 2020, 第 10 作者
（26） USP28 and USP25 are downregulated by Vismodegib in vitro and in colorectal cancer cell lines, FEBS JOURNAL, 2020, 第 12 作者
（27） Structural and functional studies of USP20 ZnF-UBP domain by NMR, PROTEIN SCIENCE, 2019, 第 11 作者
（28） Small-molecule targeting of oncogenic FTO demethylase in acute myeloid leukemia, CANCER CELL, 2019, 第 22 作者
（29） The identification of novel small-molecule inhibitors targeting WDR5-MLL1 interaction through fluorescence polarization based high-throughput screening, BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2019, 第 7 作者
（30） Fragment-based drug discovery of triazole inhibitors to block PDE��-RAS protein-protein interaction, EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, 2019, 第 14 作者
（31） Discovery of alkoxy benzamide derivatives as novel BPTF bromodomain inhibitors via structure-based virtual screening, BIOORGANIC CHEMISTRY, 2019, 第 12 作者
（32） Discovery and biological evaluation of vinylsulfonamide derivatives as highly potent, covalent TEAD autopalmitoylation inhibitors, EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, 2019, 第 16 作者
（33） Fragment-based drug discovery of triazole inhibitors to block PDE delta-RAS protein-protein interaction, EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, 2019, 第 11 作者
（34） Interplay between Alzheimer’s disease and global glucose metabolism revealed by the metabolic profile alterations of pancreatic tissue and serum in APP/PS1 transgenic mice, Interplay between Alzheimer's disease and global glucose metabolism revealed by the metabolic profile alterations of pancreatic tissue and serum in APP/PS1 transgenic mice, ACTA PHARMACOLOGICA SINICA, 2019, 第 11 作者
（35） Tetramerized Sesquiterpenoid Ainsliatetramers A and B from Ainsliaea fragrans and Their Cytotoxic Activities, ORGANIC LETTERS, 2019, 第 8 作者
（36） Extra Sugar on Vancomycin: New Analogues for Combating Multidrug-Resistant Staphylococcus aureus and Vancomycin-Resistant Enterococci., JOURNALOFMEDICINALCHEMISTRY, 2018, 第 7 作者
（37） Identification and Characterizations of Novel, Selective Histone Methyltransferase SET7 Inhibitors by Scaffold Hopping- and 2D-Molecular Fingerprint-Based Similarity Search, MOLECULES, 2018, 第 7 作者
（38） Pharmacokinetics-Based Identification of Potential Therapeutic Phthalides from XueBiJing, a Chinese Herbal Injection Used in Sepsis Management, DRUG METABOLISM AND DISPOSITION, 2018, 第 14 作者
（39） Quinone skeleton as a new class of irreversible inhibitors against Staphylococcus aureus sortase A, BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2018, 第 11 作者
（40） Discovery of 1,8-acridinedione derivatives as novel GCN5 inhibitors via high throughput screening, EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, 2018, 第 8 作者
（41） Pharmacological inhibition of dihydroorotate dehydrogenase induces apoptosis and differentiation in acute myeloid leukemia cells, HAEMATOLOGICA, 2018, 第 8 作者
（42） Discovery of potent DOT1L inhibitors by AlphaLISA based High Throughput Screening assay, BIOORGANIC & MEDICINAL CHEMISTRY, 2018, 第 7 作者
（43） H-1, C-13 and N-15 backbone and side-chain resonance assignments of the ZnF-UBP domain of USP20/VDU2, BIOMOLECULAR NMR ASSIGNMENTS, 2017, 第 11 作者
（44） An enhanced targeted identification strategy for the selective identification of flavonoid O-glycosides from Carthamus tinctorius by integrating offline two-dimensional liquid chromatography/linear ion-trap-Orbitrap mass spectrometry, high-resolution diagnostic product ions/neutral loss filtering and liquid chromatography-solid phase extraction-nuclear magnetic resonance, JOURNAL OF CHROMATOGRAPHY A, 2017, 第 5 作者
（45） Facile preparation of a symmetric hexavalent oleanolic acid/per-O-methylated alpha-cyclodextrin conjugate with two conformations in solution and unambiguous NMR analysis, TETRAHEDRON, 2017, 第 4 作者
（46） Development of Potent Type I Protein Arginine Methyltransferase (PRMT) Inhibitors of Leukemia Cell Proliferation., JOURNAL OF MEDICINAL CHEMISTRY, 2017, 第 12 作者
（47） Structural and Functional Investigations of the N-Terminal Ubiquitin Binding Region of Usp25, BIOPHYSICAL JOURNAL, 2017, 第 11 作者
（48） Metabolic profiling: shedding new light on the pathophysiological process and prognosis of HBV-related acute-on-chronic liver failure, INTERNATIONAL JOURNAL OF CLINICAL AND EXPERIMENTAL MEDICINE, 2017, 第 11 作者
（49） Metabolomic investigation of regional brain tissue dysfunctions induced by global cerebral ischemia, BMC NEUROSCIENCE, 2016, 第 11 作者
（50） Rpn1 provides adjacent receptor sites for substrate binding and deubiquitination by the proteasome, SCIENCE, 2016, 第 8 作者
（51） Identification of novel small-molecule inhibitors targeting menin-MLL interaction, repurposing the antidiarrheal loperamide, ORGANIC & BIOMOLECULAR CHEMISTRY, 2016, 第 13 作者
（52） Small-molecule targeting of a diapophytoene desaturase inhibits S. aureus virulence, NATURE CHEMICAL BIOLOGY, 2016, 第 13 作者
（53） 基于核磁共振技术研究脑缺血再灌注大鼠脑皮质代谢物组水平变化的分子机制, Molecular mechanism of metabolic changes in rat cerebral cortex after cerebral ischemia-reperfusion : an NMR- based study, 第二军医大学学报, 2016, 第 5 作者
（54） NMR-based platform for fragment-based lead discovery used in screening BRD4-targeted compounds, ACTA PHARMACOLOGICA SINICA, 2016, 第 11 作者
（55） MCAO大鼠脑缺血再灌注损伤机制的核磁共振代谢组学研究, NMR-based metabolomic investigation of regional brain tissue dysfunctions of MCAO rats induced by ischemia, 中国药科大学学报, 2016, 第 5 作者
（56） Two-Quartet G-Quadruplexes Formed by DNA Sequences Containing Four Contiguous GG Runs, JOURNAL OF PHYSICAL CHEMISTRY B, 2015, 第 5 作者
（57） The N-terminal ubiquitin-binding region of ubiquitin-specific protease 28 modulates its deubiquitination function: NMR structural and mechanistic insights, BIOCHEMICAL JOURNAL, 2015, 第 7 作者
（58） A Dynamic View of ATP-coupled Functioning Cycle of Hsp90 N-terminal Domain, SCIENTIFIC REPORTS, 2015, 第 7 作者
（59） The Intervention Effects of Acupuncture on Fatigue Induced by Exhaustive Physical Exercises: A Metabolomics Investigation, EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE, 2015, 第 4 作者
（60） Fragment-Based Drug Discovery of 2-Thiazolidinones as BRD4 Inhibitors: 2. Structure-Based Optimization, JOURNAL OF MEDICINAL CHEMISTRY, 2015, 第 8 作者
（61） H-1, C-13 and N-15 backbone and side-chain resonance assignments of the N-terminal ubiquitin-binding domains of USP25, BIOMOLECULAR NMR ASSIGNMENTS, 2014, 第 11 作者
（62） H-1, C-13 and N-15 backbone and side-chain resonance assignments of the N-terminal ubiquitin-binding domains of the human deubiquitinase Usp28, BIOMOLECULARNMRASSIGNMENTS, 2014, 第 11 作者
（63） Identification of a new series of potent diphenol HSP90 inhibitors by fragment merging and structure-based optimization, BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2014, 第 10 作者
（64） Cordyceps sinensis protects against liver and heart injuries in a rat model of chronic kidney disease: a metabolomic analysis, ACTA PHARMACOLOGICA SINICA, 2014, 第 13 作者
（65） Astemizole arrests the proliferation of cancer cells by disrupting the EZH2-EED interaction of polycomb repressive complex 2., JOURNAL OF MEDICINAL CHEMISTRY, 2014, 第 0 作者
（66） Virtual screening and biological evaluation of novel small molecular inhibitors against protein arginine methyltransferase 1 (PRMT1), ORGANIC & BIOMOLECULAR CHEMISTRY, 2014, 第 7 作者
（67） Metabolomic Analysis of Anti-Hypoxia and Anti-anxiety Effects of Fu Fang Jin Jing Oral Liquid, PLOS ONE, 2013, 第 9 作者
（68） 基于片段的药物发现方法进展, 药学学报, 2013, 第 7 作者
（69） Fragment-Based Drug Discovery of 2-Thiazolidinones as Inhibitors of the Histone Reader BRD4 Bromodomain, JOURNAL OF MEDICINAL CHEMISTRY, 2013, 第 14 作者
（70） NMR技术在蛋白质-蛋白质相互作用研究中的应用——泛素-蛋白水解酶体通路研究实例介绍, Protein-Protein Interactions Studied by NMR --A Review Using the Ubiquitin-Proteasome Pathway as Example, 波谱学杂志, 2012, 第 1 作者
（71） Dynamic behaviour of ubiquitin receptor S5a in free and complex with K48-linked diubiquitin, MOLECULAR SIMULATION, 2012, 第 11 作者
（72） Solution structure of BmK alpha Tx11, a toxin from the venom of the Chinese scorpion Buthus martensii Karsch, BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 2010, 第 5 作者
（73） Insights into how protein dynamics affects arylamine N -acetyltransferase catalysis, BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 2009, 第 1 作者
（74） Structure of the S5a:K48-Linked Diubiquitin Complex and Its Interactions with Rpn13, MOLECULAR CELL, 2009, 第 1 作者
（75） Probing the catalytic potential of the hamster arylamine N-acetyltransferase 2 catalytic triad by site-directed mutagenesis of the proximal conserved residue, Tyr190, FEBS JOURNAL, 2009, 第 2 作者
（76） Rpn10 Protects the Proteasome from Dsk2, MOLECULARCELL, 2008, 第 2 作者
（77） Proteasome subunit Rpn13 is a novel ubiquitin receptor, NATURE, 2008, 第 3 作者
（78） BmK-bIT， 一个在重要位置没有“热点”的激动型蝎毒素的NMR溶液结构, NMR solution structure of BmK-beta IT, an excitatory scorpion beta-toxin without a 'hot spot' at the relevant position structure, BIOCHEM. BIOPHYS. RES. COMMUN., 2006, 第 8 作者
（79） α-KTx 16亚家族钾通道堵塞肽BmTx3B的溶液结构, The solution structure of BmTx3B, a member of the scorpion toxin subfamily alpha-KTx, PROTEINS, 2005, 第 3 作者
（80） 马氏钳蝎蝎毒短肽BmK622的分离纯化和一级结构测定, Purification and Primary Structure of a Toxin-like Peptide BmK622 from the Venom of Chinese Scorpion Buthus martensii Karsch, 化学学报, 2003, 第 1 作者
（81） 马氏钳蝎毒液中的呔α 类神经毒素BmK16 的纯化， 表征和 1H NMR信号归属, Purification, characterization and ~1H NMR resonance assignment of an ��-like neurotoxin BmK16 from the vanom of Chinese scorpion buthus martensi karsch, CHIN. J. CHEM., 2003, 第 1 作者
（82） BmKK4， 从马氏钳蝎毒液中得到的新颖毒素体外抑制海马神经元的钾离子电流, BmKK4, a novel toxin from the venom of Asian scorpion Buthus martensi Karsch, inhibits potassium current in rat hippocampal neurons in vitro, TOXICON, 2003, 第 2 作者
（83） 马氏钳蝎蝎毒短肽BmK622的分离纯化和一级结构测定 BmK622 from the venom of chinese scorpion buthus martensii karsch, Purification and primary structure of a toxin-like peptide, 化学学报, 2003, 第 1 作者
（84） 东亚钳蝎中新分离的毒素BmTx3B抑制大鼠海马神经元延迟整流性钾电流, 中国药理学报：英文版, 2003, 第 4 作者
（85） 中药虎杖中的双二苯乙烯苷类化合物, Dimeric stilbene glycosides from polygonum suspidatum, EUR. J. ORG. CHEM., 2002, 第 8 作者
（86） 细胞色素b5突变体V45H的初步研究, NMR preliminary study on cytochrome b5 mutant V45H, 化学学报, 2001, 第 2 作者
（87） 马氏钳蝎毒素中多肽BmK4112的分离纯化和一级结构测定, Purification and primary structure of a novel peptide from the Chinese scorpion buthus martensi karsch, 生物化学与生物物理学报, 2000, 第 3 作者
（88） 香樟子糖蛋白B链糖肽的结构研究, Structural studies of the glycopetides of B-chain of chinnamomin-a type II ribosome-inactivating protein by nuclear magnetic resonance, GLYCOCONJUGATE J., 2000, 第 4 作者
（89） 马氏钳蝎毒素中多肽BmK4112的分离纯化和一级结构测定, Purification and primary structure of a novel peptide from the Chinese scorpion buthus martensi karsch, 生物化学与生物物理学报, 2000, 第 2 作者
（90） The Intervention Effects of Acupuncture on Fatigue Induced by Exhaustive Physical Exercises: A Metabolomics Investigation, EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE : ECAM, 第 4 作者