基本信息
杨德华  男  博导  中国科学院上海药物研究所
电子邮件: dhyang@simm.ac.cn
通信地址: 上海市浦东新区金科路3728号5号楼
邮政编码: 201204

招生信息

   
招生专业
100706-药理学
招生方向
G蛋白偶联受体的结构和功能
G蛋白偶联受体的小分子药物筛选

教育背景

2005-09--2009-12   中国科学院上海生命科学研究院   博士研究生/博士
2002-09--2005-07   华南师范大学   硕士研究生/硕士
1997-09--2002-07   烟台师范学院   本科/学士

工作经历

   
工作简历
2017-10~现在, 中国科学院上海药物研究所, 研究员
2012-10~2017-09,中国科学院上海药物研究所, 副研究员
2012-03~2012-09,中国科学院上海药物研究所, 助理研究员
2010-01~2012-02,上海交通大学医学院, 博士后
2005-09~2009-12,中国科学院上海生命科学研究院, 博士研究生/博士
2002-09~2005-07,华南师范大学, 硕士研究生/硕士
1997-09~2002-07,烟台师范学院, 本科/学士

教授课程

药物筛选

专利与奖励

   
奖励信息
(1) 上海市优秀学术带头人, 省级, 2023
(2) 赛诺菲—中国科学院上海生命科学研究院优秀青年人才奖, 研究所(学校), 2017
(3) 上海市人才发展基金, 省级, 2016
(4) 科技部及盖茨基金会“大挑战·青年科学家”奖, 部委级, 2015
(5) 中华医学科技奖, 二等奖, 部委级, 2008
(6) 上海市科学技术奖, 三等奖, 省级, 2008
(7) 上海市医学科技奖, 二等奖, 其他, 2008
专利成果
( 1 ) 新型四氢异喹啉类化合物、其制备方法、包含此类化合物的药物组合物及其用途, 2022, 第 2 作者, 专利号: 2022105572849

( 2 ) 苯甲酰胺类化合物及其制备方法、药物组合物和用途, 2021, 第 6 作者, 专利号: CN112812077A

( 3 ) 一类取代三环结构的化合物、其制备方法及用途, 2021, 第 1 作者, 专利号: CN112745319A

( 4 ) 3,4,5-三取代吡唑类化合物、制备方法、药物组合物及用途, 2017, 第 4 作者, 专利号: CN106279023A

出版信息

   
发表论文
(1) Effects of site-directed mutagenesis of GLP-1 and glucagon receptors on signal transduction activated by dual and triple agonists, Effects of site-directed mutagenesis of GLP-1 and glucagon receptors on signal transduction activated by dual and triple agonists, ACTA PHARMACOLOGICA SINICA, 2023, 通讯作者
(2) Preparing high-concentration individualized carbon nanotubes for industrial separation of multiple single-chirality species, NATURE COMMUNICATIONS, 2023, 第 1 作者
(3) Ligand recognition mechanism of the human relaxin family peptide receptor 4 (RXFP4), NATURE COMMUNICATIONS, 2023, 通讯作者
(4) Modulating effects of RAMPs on signaling profiles of the glucagon receptor family, Modulating effects of RAMPs on signaling profiles of the glucagon receptor family, ACTA PHARMACEUTICA SINICA B, 2022, 通讯作者
(5) Molecular recognition of two endogenous hormones by the human parathyroid hormone receptor-1, ACTA PHARMACOLOGICA SINICA, 2022, 通讯作者
(6) A distinctive ligand recognition mechanism by the human vasoactive intestinal polypeptide receptor 2, NATURE COMMUNICATIONS, 2022, 通讯作者
(7) Signaling profiles in HEK 293T cells co-expressing GLP-1 and GIP receptors, Signaling profiles in HEK 293T cells co-expressing GLP-1 and GIP receptors, ACTA PHARMACOLOGICA SINICA, 2022, 通讯作者
(8) GLP-1 mimetics as a potential therapy for nonalcoholic steatohepatitis, GLP-1 mimetics as a potential therapy for nonalcoholic steatohepatitis, ACTA PHARMACOLOGICA SINICA, 2022, 通讯作者
(9) Structural basis of peptidomimetic agonism revealed by small-molecule GLP-1R agonists Boc5 and WB4-24, PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2022, 通讯作者
(10) Cryo-EM structures of cancer-specific helical and kinase domain mutations of PI3Kα, PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2022, 通讯作者
(11) Structural insights into ligand recognition and selectivity of somatostatin receptors, CELLRESEARCH, 2022, 通讯作者
(12) Nanobodies and chemical cross-links advance the structural and functional analysis of PI3Kα, PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2022, 通讯作者
(13) Structural insights into multiplexed pharmacological actions of tirzepatide and peptide 20 at the GIP, GLP-1 or glucagon receptors, NATURE COMMUNICATIONS, 2022, 通讯作者
(14) A high-throughput screening campaign against PFKFB3 identified potential inhibitors with novel scaffolds, ACTA PHARMACOLOGICA SINICA, 2022, 通讯作者
(15) Design, synthesis and pharmacological evaluation of tricyclic derivatives as selective RXFP4 agonists, BIOORGANIC CHEMISTRY, 2021, 通讯作者
(16) Structures of the human cholecystokinin receptors bound to agonists and antagonists, NATURE CHEMICAL BIOLOGY, 2021, 第 5 作者
(17) Constitutive signal bias mediated by the human GHRHR splice variant 1, PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2021, 通讯作者
(18) W2476 represses TXNIP transcription via dephosphorylation of FOXO1 at Ser319, CHEMICAL BIOLOGY & DRUG DESIGN, 2021, 通讯作者
(19) Discovery of Novel Allosteric Modulators Targeting an Extra-Helical Binding Site of GLP-1R Using Structure- and Ligand-Based Virtual Screening, BIOMOLECULES, 2021, 通讯作者
(20) Ligand recognition and G-protein coupling selectivity of cholecystokinin A receptor, NATURE CHEMICAL BIOLOGY, 2021, 第 2 作者
(21) Molecular insights into ago-allosteric modulation of the human glucagon-like peptide-1 receptor, NATURE COMMUNICATIONS, 2021, 通讯作者
(22) Structures of Gi-bound metabotropic glutamate receptors mGlu2 and mGlu4, NATURE, 2021, 第 17 作者
(23) Structural insights into hormone recognition by the human glucose-dependent insulinotropic polypeptide receptor, ELIFE, 2021, 通讯作者
(24) G protein-coupled receptors: structure- and function-based drug discovery, G protein-coupled receptors: structure- and function-based drug discovery, SIGNAL TRANSDUCTION AND TARGETED THERAPY, 2021, 第 1 作者
(25) GPR160 is a potential biomarker associated with prostate cancer, GPR160 is a potential biomarker associated with prostate cancer, SIGNAL TRANSDUCTION AND TARGETED THERAPY, 2021, 通讯作者
(26) Deleterious mutation V369M in the mouse GCGR gene causes abnormal plasma amino acid levels indicative of a possible liver & ndash;alpha-cell axis, BIOSCIENCE REPORTS, 2021, 通讯作者
(27) Cryo-EM structures of PI3K alpha reveal conformational changes during inhibition and activation, PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2021, 通讯作者
(28) High-Throughput Screening Campaign Identified a Potential Small Molecule RXFP3/4 Agonist, MOLECULES, 2021, 通讯作者
(29) Molecular insights into differentiated ligand recognition of the human parathyroid hormone receptor 2, PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2021, 通讯作者
(30) Structural insights into ligand recognition and activation of the melanocortin-4 receptor, CELL RESEARCH, 2021, 第 3 作者
(31) High-throughput screening campaign identifies a small molecule agonist of the relaxin family peptide receptor 4, High-throughput screening campaign identifies a small molecule agonist of the relaxin family peptide receptor 4, ACTA PHARMACOLOGICA SINICA, 2020, 通讯作者
(32) Structural basis for activation of the growth hormone-releasing hormone receptor, NATURE COMMUNICATIONS, 2020, 通讯作者
(33) An in vitro Forster resonance energy transfer-based high-throughput screening assay identifies inhibitors of SUMOylation E2 Ubc9, An in vitro Fo''rster resonance energy transfer-based high-throughput screening assay identifies inhibitors of SUMOylation E2 Ubc9, ACTA PHARMACOLOGICA SINICA, 2020, 通讯作者
(34) Structural basis of G(s) and G(i) recognition by the human glucagon receptor, SCIENCE, 2020, 第 14 作者
(35) A unique hormonal recognition feature of the human glucagon-like peptide-2 receptor, A unique hormonal recognition feature of the human glucagon-like peptide-2 receptor, CELL RESEARCH, 2020, 第 5 作者
(36) Structures of Gi-bound metabotropic glutamate receptors mGlu2 and mGlu4, NATURE, 2020, 第 17 作者
(37) Identification of catalytic and non-catalytic activity inhibitors against PRC2-EZH2 complex through multiple high-throughput screening campaigns, CHEMICAL BIOLOGY & DRUG DESIGN, 2020, 通讯作者
(38) Accelerating the Throughput of Affinity Mass Spectrometry-Based Ligand Screening toward a G Protein-Coupled Receptor, ANALYTICAL CHEMISTRY, 2019, 第 8 作者
(39) Selective activation of TWIK-related acid-sensitive K+ 3 subunit-containing channels is analgesic in rodent models, SCIENCE TRANSLATIONAL MEDICINE, 2019, 第 20 作者
(40) Structure and dynamics of the active human parathyroid hormone receptor-1, SCIENCE, 2019, 其他(合作组作者)
(41) Integrating yeast chemical genomics and mammalian cell pathway analysis, Integrating yeast chemical genomics and mammalian cell pathway analysis, ACTA PHARMACOLOGICA SINICA, 2019, 第 8 作者
(42) DeepCPI:A Deep Learning-based Framework for Large-scale in silico Drug Screening, deepcpiadeeplearningbasedframeworkforlargescaleinsilicodrugscreening, GENOMICS PROTEOMICS & BIOINFORMATICS, 2019, 通讯作者
(43) Common activation mechanism of class A GPCRs, ELIFE, 2019, 第 2 作者
(44) Synthesis of Aryl Propionamide Scaffold Containing a Pentafluorosulfanyl Moiety as SARMs, MOLECULES, 2019, 第 3 作者
(45) Orthogonal assays for the identification of inhibitors of the single-stranded nucleic acid binding protein YB-1, ACTA PHARMACEUTICA SINICA B, 2019, 第 3 作者
(46) High-throughput identification of G protein-coupled receptor modulators through affinity mass spectrometry screening, CHEMICAL SCIENCE, 2018, 第 3 作者
(47) High-throughput screening for small molecule inhibitors of the type-I interferon signaling pathway, High-throughput screening for small molecule inhibitors of the type-I interferon signaling pathway, ACTA PHARMACEUTICA SINICA B, 2018, 第 3 作者
(48) A novel series of 4-methyl substituted pyrazole derivatives as potent glucagon receptor antagonists: Design, synthesis and evaluation of biological activities, BIOORGANIC & MEDICINAL CHEMISTRY, 2018, 第 8 作者
(49) Two distinct domains of the glucagon-like peptide-1 receptor control peptide-mediated biased agonism, JOURNAL OF BIOLOGICAL CHEMISTRY, 2018, 第 6 作者
(50) Identification, structure modification, and characterization of potential small-molecule SGK3 inhibitors with novel scaffolds, ACTA PHARMACOLOGICA SINICA, 2018, 第 7 作者
(51) Structure of the glucagon receptor in complex with a glucagon analogue, NATURE, 2018, 第 6 作者
(52) Extracellular loops 2 and 3 of the calcitonin receptor selectively modify agonist binding and efficacy, BIOCHEMICAL PHARMACOLOGY, 2018, 第 7 作者
(53) Chemical Diversity in the G Protein-Coupled Receptor Superfamily, TRENDS IN PHARMACOLOGICAL SCIENCES, 2018, 第 3 作者
(54) High-throughput screening campaigns against a PI3Kα isoform bearing the H1047R mutation identified potential inhibitors with novel scaffolds, highthroughputscreeningcampaignsagainstapi3kisoformbearingtheh1047rmutationidentifiedpotentialinhibitorswithnovelscaffolds, ACTAPHARMACOLOGICASINICA, 2018, 其他(合作组作者)
(55) Crystal structure of the human 5-HT1B serotonin receptor bound to an inverse agonist, CELL DISCOVERY, 2018, 第 3 作者
(56) High-throughput screening campaigns against a PI3K alpha isoform bearing the H1047R mutation identified potential inhibitors with novel scaffolds, ACTA PHARMACOLOGICA SINICA, 2018, 其他(合作组作者)
(57) Synthesis of androgen receptor antagonists containing a pentafluorosulfanyl (SF5) moiety, ARCHIV DER PHARMAZIE, 2018, 第 3 作者
(58) Discovery of thiophene-containing biaryl amide derivatives as novel glucagon receptor antagonists, CHEMICAL BIOLOGY & DRUG DESIGN, 2018, 第 8 作者
(59) Adenine derivatives invert high glucose-induced thioredoxin-interacting protein overexpression, CHEMICAL BIOLOGY & DRUG DESIGN, 2018, 第 6 作者
(60) Rearrangement of a polar core provides a conserved mechanism for constitutive activation of class B G protein-coupled receptors, JOURNAL OF BIOLOGICAL CHEMISTRY, 2017, 第 5 作者
(61) Cycloalkane analogues of sinefungin as EHMT1/2 inhibitors, BIOORGANIC & MEDICINAL CHEMISTRY, 2017, 第 3 作者
(62) W2476 ameliorates beta-cell dysfunction and exerts therapeutic effects in mouse models of diabetes via modulation of the thioredoxin-interacting protein signaling pathway, ACTA PHARMACOLOGICA SINICA, 2017, 第 13 作者
(63) Human GLP-1 receptor transmembrane domain structure in complex with allosteric modulators, NATURE, 2017, 第 2 作者
(64) Structure of the full-length glucagon class B G-protein-coupled receptor, NATURE, 2017, 第 3 作者
(65) Differential Requirement of the Extracellular Domain in Activation of Class B G Protein-coupled Receptors, JOURNAL OF BIOLOGICAL CHEMISTRY, 2016, 第 3 作者
(66) A historic study that opened a new chapter in nutritional science, ACTA PHARMACOLOGICA SINICA, 2016, 第 2 作者
(67) Design, synthesis, structure–activity relationships, and docking studies of pyrazole-containing derivatives as a novel series of potent glucagon receptor antagonists, BIOORGANIC & MEDICINAL CHEMISTRY, 2016, 第 7 作者
(68) Glucagon-Like Peptide-1 and Its Class B G Protein–Coupled Receptors: A Long March to Therapeutic Successes, PHARMACOLOGICAL REVIEWS, 2016, 第 10 作者
(69) Structural Determinants of Binding the Seven-transmembrane Domain of the Glucagon-like Peptide-1 Receptor (GLP-1R), JOURNAL OF BIOLOGICAL CHEMISTRY, 2016, 第 1 作者
(70) Landmark studies on the glucagon subfamily of GPCRs: from small molecule modulators to a crystal structure, ACTA PHARMACOLOGICA SINICA, 2015, 第 1 作者
(71) Critical Role of Tet3 in Neural Progenitor Cell Maintenance and Terminal Differentiation, MOLECULAR NEUROBIOLOGY, 2015, 第 2 作者
(72) Conformational states of the full-length glucagon receptor, NATURE COMMUNICATIONS, 2015, 
(73) The Radical Scavenger Edaravone Improves Neurologic Function and Perihematomal Glucose Metabolism after Acute Intracerebral Hemorrhage, JOURNAL OF STROKE & CEREBROVASCULAR DISEASES, 2015, 第 3 作者
(74) Graphene oxide promotes the differentiation of mouse embryonic stem cells to dopamine neurons, NANOMEDICINE, 2014, 第 1 作者
(75) Genome-wide mapping of miRNAs expressed in embryonic stem cells and pluripotent stem cells generated by different reprogramming strategies, BMC GENOMICS, 2014, 第 2 作者
(76) The putative signal peptide of glucagon-like peptide-1 receptor is not required for receptor synthesis but promotes receptor expression, BIOSCIENCE REPORTS, 2014, 第 2 作者
(77) 依达拉奉对脑出血大鼠脑代谢的改善作用及其机制研究, Edaravone improves neurological functions and perihematomal glucose metabolism in acute intracerebral hemorrhagic rats and its mechanism, 中华神经外科疾病研究杂志, 2014, 第 2 作者
(78) Time course of Keap1-Nrf2 pathway expression after experimental intracerebral haemorrhage: correlation with brain oedema and neurological deficit, FREE RADICAL RESEARCH, 2013, 
(79) g蛋白偶联受体别构调节剂, 生命的化学, 2013, 第 2 作者
(80) 依达拉奉激活Nrf2通路减轻脑出血后继发性损伤, Edaravone attenuate secondary brain injury after intracerebral hemorrhage through activating Nrf2 pathway, 中华神经外科疾病研究杂志, 2013, 第 3 作者
(81) High-Throughput Screening for GPR119 Modulators Identifies a Novel Compound with Anti-Diabetic Efficacy in db/db Mice, PLOS ONE, 2013, 第 7 作者
(82) Structure of the human glucagon class B G-protein-coupled receptor, NATURE, 2013, 第 5 作者
(83) Mifepristone-Inducible Caspase-1 Expression in Mouse Embryonic Stem Cells Eliminates Tumor Formation but Spares Differentiated Cells In Vitro and In Vivo, STEM CELLS, 2012, 第 2 作者
(84) miR-132 regulates the differentiation of dopamine neurons by directly targeting Nurr1 expression, JOURNAL OF CELL SCIENCE, 2012, 第 1 作者
(85) Long-Term Treatment with Lithium Alleviates Memory Deficits and Reduces Amyloid-beta Production in an Aged Alzheimer's Disease Transgenic Mouse Model, JOURNAL OF ALZHEIMERS DISEASE, 2011, 第 5 作者
(86) c-Jun N-terminal kinase mediates lactacystin-induced dopamine neuron degeneration, JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY, 2008, 第 4 作者
(87) Rearrangement of a polar core provides a conserved mechanism for constitutive activation of class B G protein-coupled receptors, THE JOURNAL OF BIOLOGICAL CHEMISTRY, 第 5 作者
(88) Differential Requirement of the Extracellular Domain in Activation of Class B G Protein-coupled Receptors *, THE JOURNAL OF BIOLOGICAL CHEMISTRY, 第 3 作者
(89) Structural Determinants of Binding the Seven-transmembrane Domain of the Glucagon-like Peptide-1 Receptor (GLP-1R) *, THE JOURNAL OF BIOLOGICAL CHEMISTRY, 第 1 作者

科研活动

   
科研项目
( 1 ) 基于非肽类小分子激动剂Boc5的GLP-1R别构调节剂的功能和应用研究, 负责人, 国家任务, 2014-01--2017-12
( 2 ) GLP-1受体别构调节剂筛选及其在糖尿病中的功能研究, 负责人, 地方任务, 2012-07--2015-06
( 3 ) 针对重要癌基因靶点的个性化抗癌新药开发, 参与, 国家任务, 2014-04--2017-03
( 4 ) 基于促肾上腺皮质激素释放因子1型受体蛋白晶体结构的创新药物发现和成药性研究, 参与, 地方任务, 2014-07--2017-09
( 5 ) 基于B族GPCR蛋白晶体结构阐明GLP-1R跨膜区关键位点的功能, 负责人, 国家任务, 2016-01--2019-12
( 6 ) Functional studies and signal bias exploration on GLP-lR transmembrane domains, 负责人, 中国科学院计划, 2016-01--2017-12
( 7 ) 针对糖尿病新靶标RXFP4的先导化合物发现, 负责人, 中国科学院计划, 2016-01--2017-12
( 8 ) 基于受体蛋白结构信息阐释GLP-1R和GCGR受体选择性的分子机制, 负责人, 国家任务, 2018-01--2021-12
( 9 ) 胰高血糖素家族GPCR的受体间相互作用及其多重药理学分子机制的研究, 负责人, 国家任务, 2020-01--2023-12
( 10 ) 基于结构信息的非肽类GLP-1R激动剂结合口袋解析和药理机制研究, 负责人, 国家任务, 2023-01--2026-12
( 11 ) 前列腺癌关键靶标GPR160的内源性配体鉴定和作用机理研究, 负责人, 地方任务, 2021-10--2024-09
( 12 ) G蛋白偶联受体结构药理学, 参与, 国家任务, 2022-01--2026-12
( 13 ) 深海深渊微生物活性物质资源研究, 负责人, 地方任务, 2021-12--2024-12