新陈代谢
简历：
1996 年毕业于北京大学化学系，获理学学士学位，同年赴美学习研究生课程，并于 2002 年获得美国新泽西医科和牙科大学神经科学专业的博士学位。
随后，转入新泽西医学院从事神经生物学 方面的 博士后研究工作。2004 年加入国家新药筛选中心担任模型建立 II 部主管，从事基于 G 蛋白偶联受体的信号转导通路研究及高通量 / 高内涵药物筛选模型建立及应用工作。 2005 年入选上海市 “ 浦江人才计划 ” ，中国科学院 “ 百人计划 ” （ 2006 年获择优资助），中国科学院上海药物研究所研究员。
电子邮件:
xxie@mail.shcnc.ac.cn
通讯地址:
上海市郭守敬路189号，国家新药筛选中心 201203
研究方向：
基于G蛋白偶联受体的创新药物发现及研究:
G蛋白偶联受体家族（G-Protein-Coupled Receptor, GPCR）是人体内最大的膜受体蛋白家族。目前已知有近一千个基因编码GPCR。GPCR都具有典型的七次跨膜结构，对多种细胞外刺激如光、气味、离子、神经递质、趋化因子、脂类、肽类和激素等产生反应，介导多种重要的生理功能。GPCR在信号转导通路的源头位置及其介导的生理功能的多样性使其成为最具开发潜力的药物作用靶点，目前市场上有约40％的药物是直接或间接作用与GPCR的。
我们选择这一重要的药物作用靶点家族，开展以下几方面的工作：
1． G蛋白偶联受体高通量/高内涵筛选模型的建立。我们将选择与重大疾病相关的GPCR（如与肥胖症密切相关的大麻受体CB1和黑色素皮质素受体MC4；与爱滋病相关的趋化因子受体CCR5和CXCR4以及与神经系统疾病相关的受体等），应用分子及细胞生物学知识及实验技巧构建稳定表达受体的细胞系，通过受配体竞争结合、GTPS结合、报告基因检测、胞内cAMP检测、钙流检测、受体位移、受体下游信号蛋白位移等方法建立高通量/高内涵筛选模型。
2． 基于重大疾病相关的G蛋白偶联受体靶点的新药筛选。我们将应用上述高通量/高内涵筛选模型对合成或天然来源的化合物进行筛选、验证，以期发现新型小分子药物先导化合物，为进一步结构改造和优化打下基础。
3． G蛋白偶联受体信号转导通路研究。传统GPCR 信号转导研究集中在G蛋白亚型与第二信使激活等方面。近期研究发现GPCR还可以和多种膜蛋白及下游信号蛋白直接作用。另我们也发现活性小分子化合物与天然配体的活化作用之间存在一定差异，这可能与受配体间结合部位差异而导致不同的下游信号转导有关。我们希望利用已有的活性小分子化合物为探针，利用化学生物学方法对G蛋白偶联受体信号转导通路进行进一步研究。
专家类别：
研究员；百人计划
职务：
中科院上海药物所研究员、博士生导师、研究组长
承担科研项目情况：
参加或主持了多项国家、科学院及地方的科研项目。科技部重大科学研究计划项目首席科学家。
获奖及荣誉：
代表论著：
近期发表论文选录
Xu Y, Xie X*. Glucagon receptor mediates calcium signaling by coupling to Gaq/11 and Gai/o in HEK293 cells. Journal of Receptors and Signal Transduction. 2009. Accepted.
Wang L-F, Zhang R, Xie X*. Development of a high throughput assay for screening of γ-secretase inhibitor with endogenous human, mouse or drosophila γ-secretase. Molecules. 2009. Accepted.
Li F, Yin C, Chen J, Liu J, Xie X, Zhang A. Synthesis and SAR Study of Opioid Receptor Ligands: Mono- and Bis-Indolomorphinans. Chem Biol Drug Des. 2009 Aug 19. [Epub ahead of print]
Wu G, Xie X, Lu ZH, Ledeen RW. Sodium-calcium exchanger complexed with GM1 ganglioside in nuclear membrane transfers calcium from nucleoplasm to endoplasmic reticulum. Proc Natl Acad Sci U S A. 2009;106(26):10829-34.
Li F, Gaob L, Yin C, Chen J, Liu J, Xie X*, Zhang A. Synthesis and opioid receptor activity of indolopropellanes. Bioorg Med Chem Lett. 2009;19(16):4603-6.
He X, Fang L, Wang J, Yi Y, Zhang S, Xie X*. Bryostatin-5 blocks SDF-1 induced chemotaxis via desensitization and down-regulation of cell surface CXCR4 receptors. Cancer Res 2008; 68(21):8678-86
Hong MH, Xu C, Wang YJ, Ji JL, Tao YM, Xu XJ, Chen J, Xie X, Chi ZQ, Liu JG. Role of Src in ligand-specific regulation of delta-opioid receptor desensitization and internalization. J Neurochem. 2008; 108(1):102-14.
Liu Y, Zhou E, Yu K, Zhu J, Zhang Y, Xie X*, Li J, Jiang H. Discovery of a novel CCR5 antagonist lead compound through fragment assembly. Molecules. 2008 Oct 1;13(10):2426-41.
Zhu T, Fang L, Xie X*. Development of a universal high-throughput calcium assay for G protein-coupled receptors with promiscuous G protein G15/16. Acta Pharmacol Sin. 2008;29(4):507-16.
Zhang L, Yu J, Pan H, Hu P, Hao Y, Cai W, Zhu H, Yu AD, Xie X, Ma D, Yuan J. Small molecule regulators of autophagy identified by an image-based high-throughput screen. Proc Natl Acad Sci U S A. 2007 Nov 27;104(48):19023-8.
Wang J, Xie X*. Development of a Quantitative Cell-Based High-Content Screening Assay for Epidermal Growth Factor Receptor Modulators. Acta Pharmacol Sin. 2007 Oct;28(10):1698-704.
Tian F, Zhu CH, Zhang XW, Xie X, Xin XL, Yi YH, Lin LP, Geng MY, Ding J. Philinopside E, a new sulfated saponin from sea cucumber, blocks the interaction between kinase insert domain-containing receptor (KDR) and alphavbeta3 integrin via binding to the extracellular domain of KDR. Mol Pharmacol. 2007 Sep;72(3):545-52.
Chen D, Liao J, Li N, Zhou C, Liu Q, Wang G, Zhang R, Zhang S, Lin L, Chen K, Xie X, Nan F, Young AA, Wang MW. A nonpeptidic agonist of glucagon-like peptide 1 receptors with efficacy in diabetic db/db mice. Proc Natl Acad Sci U S A. 2007 Jan 16;104(3):943-8.
Yan P, Nanamori M, Sun M, Zhou C, Cheng N, Li N, Zheng W, Xiao L, Xie X, Ye RD, Wang MW. The immunosuppressant cyclosporin A antagonizes human formyl peptide receptor through inhibition of cognate ligand binding. J Immunol. 2006 Nov 15;177(10):7050-8.
Wu G, Lu ZH, Wang J, Wang Y, Xie X, Meyenhofer MF, Ledeen RW. Enhanced susceptibility to kainate-induced seizures, neuronal apoptosis, and death in mice lacking gangliotetraose gangliosides: protection with LIGA 20, a membrane-permeant analog of GM1. Journal of Neuroscience. 2005, 25(47):11014-22.
Qinghai Tian, Jing Li, Xin Xie, Meiling Sun, Hairong Sang, Caihong Zhou, Lihong Hu, Richard D. Ye, and Ming-Wei Wang*. Stereo-specific induction of NF-kB activation by isochamaejasmin. Molecular Pharmacology. 2005, 68(6),1534-42.
Jie Gao, Xin Hui, Juan Ma, Xin Xie, Tsuyoshi Ogiku, Ming-Wei Wang*. (2005) A robust homogeneous binding assay for 42 nicotinic acetylcholine receptor. Acta Pharmacologica Sinica. 2005, 26(10),1175-80.
Xie X, Wu G, Lu ZH, Rohowsky-Kochan C, Ledeen RW.（2004）Presence of sodium-calcium exchanger/GM1 complex in the nuclear envelope of non-neural cells: nature of exchanger-GM1 interaction. Neurochem Res 29(11):2135-46.
Wu G, Lu ZH, Xie X, Ledeen RW. (2004) Susceptibility of cerebellar granule neurons from GM2/GD2 synthase-null mice to apoptosis induced by glutamate excitotoxicity and elevated KCl: rescue by GM1 and LIGA20. Glycoconj J 21(6):305-13.
Xie X, Wu G, Ledeen RW. (2004) C6 cells express a sodium-calcium exchanger/GM1 complex in the nuclear envelope but have no exchanger in the plasma membrane: Comparison to astrocytes. J Neurosci Res 76:363-75.
Xie X, Wu G, Lu ZH, Ledeen RW. (2002) Potentiation of a sodium-calcium exchanger in the nuclear envelope by nuclear GM1 ganglioside. J Neurochem 81(6):1185-95.
Fang Y, Xie X, Ledeen RW, Wu G. (2002) Characterization of cholera toxin B subunit-induced Ca2+ influx in neuroblastoma cells: Evidence for a voltage independent GM1-associated Ca2+ channel. J Neurosci Res 69:669-680.
Wu G, Xie X, Lu ZH, Ledeen RW. (2001) Cerebellar neurons lacking complex gangliosides degenerate in the presence of depolarizing levels of potassium. Proc Natl Acad Sci USA 98:307-312.
Wu G, Lu Z-H, Xie X, Li L, Ledeen RW. (2001) Mutant NG108-15 cells (NG-CR72) deficient in GM1synthase respond aberrantly to axonogenic stimuli and are vulnerable to calcium-induced apoptosis: they are rescued with Liga-20. J Neurochem 76:690-702.
Wu G, Lu Z-H, Xie X, Ledeen RW (2001) Comparison of ganglioside profiles in nuclear and whole cells of NG108-15 and NG-CR72 lines: changes in response to different neuritogenic stimuli. Devl Brain Res 126(2):183-190.
Fang Y, Wu G, Xie X, Lu Z-H, Ledeen RW. (2000) Endogenous GM1 ganglioside of the plasma membrane promotes neuritogenesis by two mechanisms. Neurochem Res 25:931-940.
1996 年毕业于北京大学化学系，获理学学士学位，同年赴美学习研究生课程，并于 2002 年获得美国新泽西医科和牙科大学神经科学专业的博士学位。
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| 谢欣 |
电子邮件:
xxie@mail.shcnc.ac.cn
通讯地址:
上海市郭守敬路189号，国家新药筛选中心 201203
研究方向：
基于G蛋白偶联受体的创新药物发现及研究:
G蛋白偶联受体家族（G-Protein-Coupled Receptor, GPCR）是人体内最大的膜受体蛋白家族。目前已知有近一千个基因编码GPCR。GPCR都具有典型的七次跨膜结构，对多种细胞外刺激如光、气味、离子、神经递质、趋化因子、脂类、肽类和激素等产生反应，介导多种重要的生理功能。GPCR在信号转导通路的源头位置及其介导的生理功能的多样性使其成为最具开发潜力的药物作用靶点，目前市场上有约40％的药物是直接或间接作用与GPCR的。
我们选择这一重要的药物作用靶点家族，开展以下几方面的工作：
1． G蛋白偶联受体高通量/高内涵筛选模型的建立。我们将选择与重大疾病相关的GPCR（如与肥胖症密切相关的大麻受体CB1和黑色素皮质素受体MC4；与爱滋病相关的趋化因子受体CCR5和CXCR4以及与神经系统疾病相关的受体等），应用分子及细胞生物学知识及实验技巧构建稳定表达受体的细胞系，通过受配体竞争结合、GTPS结合、报告基因检测、胞内cAMP检测、钙流检测、受体位移、受体下游信号蛋白位移等方法建立高通量/高内涵筛选模型。
2． 基于重大疾病相关的G蛋白偶联受体靶点的新药筛选。我们将应用上述高通量/高内涵筛选模型对合成或天然来源的化合物进行筛选、验证，以期发现新型小分子药物先导化合物，为进一步结构改造和优化打下基础。
3． G蛋白偶联受体信号转导通路研究。传统GPCR 信号转导研究集中在G蛋白亚型与第二信使激活等方面。近期研究发现GPCR还可以和多种膜蛋白及下游信号蛋白直接作用。另我们也发现活性小分子化合物与天然配体的活化作用之间存在一定差异，这可能与受配体间结合部位差异而导致不同的下游信号转导有关。我们希望利用已有的活性小分子化合物为探针，利用化学生物学方法对G蛋白偶联受体信号转导通路进行进一步研究。
专家类别：
研究员；百人计划
职务：
中科院上海药物所研究员、博士生导师、研究组长
承担科研项目情况：
参加或主持了多项国家、科学院及地方的科研项目。科技部重大科学研究计划项目首席科学家。
获奖及荣誉：
代表论著：
近期发表论文选录
Xu Y, Xie X*. Glucagon receptor mediates calcium signaling by coupling to Gaq/11 and Gai/o in HEK293 cells. Journal of Receptors and Signal Transduction. 2009. Accepted.
Wang L-F, Zhang R, Xie X*. Development of a high throughput assay for screening of γ-secretase inhibitor with endogenous human, mouse or drosophila γ-secretase. Molecules. 2009. Accepted.
Li F, Yin C, Chen J, Liu J, Xie X, Zhang A. Synthesis and SAR Study of Opioid Receptor Ligands: Mono- and Bis-Indolomorphinans. Chem Biol Drug Des. 2009 Aug 19. [Epub ahead of print]
Wu G, Xie X, Lu ZH, Ledeen RW. Sodium-calcium exchanger complexed with GM1 ganglioside in nuclear membrane transfers calcium from nucleoplasm to endoplasmic reticulum. Proc Natl Acad Sci U S A. 2009;106(26):10829-34.
Li F, Gaob L, Yin C, Chen J, Liu J, Xie X*, Zhang A. Synthesis and opioid receptor activity of indolopropellanes. Bioorg Med Chem Lett. 2009;19(16):4603-6.
He X, Fang L, Wang J, Yi Y, Zhang S, Xie X*. Bryostatin-5 blocks SDF-1 induced chemotaxis via desensitization and down-regulation of cell surface CXCR4 receptors. Cancer Res 2008; 68(21):8678-86
Hong MH, Xu C, Wang YJ, Ji JL, Tao YM, Xu XJ, Chen J, Xie X, Chi ZQ, Liu JG. Role of Src in ligand-specific regulation of delta-opioid receptor desensitization and internalization. J Neurochem. 2008; 108(1):102-14.
Liu Y, Zhou E, Yu K, Zhu J, Zhang Y, Xie X*, Li J, Jiang H. Discovery of a novel CCR5 antagonist lead compound through fragment assembly. Molecules. 2008 Oct 1;13(10):2426-41.
Zhu T, Fang L, Xie X*. Development of a universal high-throughput calcium assay for G protein-coupled receptors with promiscuous G protein G15/16. Acta Pharmacol Sin. 2008;29(4):507-16.
Zhang L, Yu J, Pan H, Hu P, Hao Y, Cai W, Zhu H, Yu AD, Xie X, Ma D, Yuan J. Small molecule regulators of autophagy identified by an image-based high-throughput screen. Proc Natl Acad Sci U S A. 2007 Nov 27;104(48):19023-8.
Wang J, Xie X*. Development of a Quantitative Cell-Based High-Content Screening Assay for Epidermal Growth Factor Receptor Modulators. Acta Pharmacol Sin. 2007 Oct;28(10):1698-704.
Tian F, Zhu CH, Zhang XW, Xie X, Xin XL, Yi YH, Lin LP, Geng MY, Ding J. Philinopside E, a new sulfated saponin from sea cucumber, blocks the interaction between kinase insert domain-containing receptor (KDR) and alphavbeta3 integrin via binding to the extracellular domain of KDR. Mol Pharmacol. 2007 Sep;72(3):545-52.
Chen D, Liao J, Li N, Zhou C, Liu Q, Wang G, Zhang R, Zhang S, Lin L, Chen K, Xie X, Nan F, Young AA, Wang MW. A nonpeptidic agonist of glucagon-like peptide 1 receptors with efficacy in diabetic db/db mice. Proc Natl Acad Sci U S A. 2007 Jan 16;104(3):943-8.
Yan P, Nanamori M, Sun M, Zhou C, Cheng N, Li N, Zheng W, Xiao L, Xie X, Ye RD, Wang MW. The immunosuppressant cyclosporin A antagonizes human formyl peptide receptor through inhibition of cognate ligand binding. J Immunol. 2006 Nov 15;177(10):7050-8.
Wu G, Lu ZH, Wang J, Wang Y, Xie X, Meyenhofer MF, Ledeen RW. Enhanced susceptibility to kainate-induced seizures, neuronal apoptosis, and death in mice lacking gangliotetraose gangliosides: protection with LIGA 20, a membrane-permeant analog of GM1. Journal of Neuroscience. 2005, 25(47):11014-22.
Qinghai Tian, Jing Li, Xin Xie, Meiling Sun, Hairong Sang, Caihong Zhou, Lihong Hu, Richard D. Ye, and Ming-Wei Wang*. Stereo-specific induction of NF-kB activation by isochamaejasmin. Molecular Pharmacology. 2005, 68(6),1534-42.
Jie Gao, Xin Hui, Juan Ma, Xin Xie, Tsuyoshi Ogiku, Ming-Wei Wang*. (2005) A robust homogeneous binding assay for 42 nicotinic acetylcholine receptor. Acta Pharmacologica Sinica. 2005, 26(10),1175-80.
Xie X, Wu G, Lu ZH, Rohowsky-Kochan C, Ledeen RW.（2004）Presence of sodium-calcium exchanger/GM1 complex in the nuclear envelope of non-neural cells: nature of exchanger-GM1 interaction. Neurochem Res 29(11):2135-46.
Wu G, Lu ZH, Xie X, Ledeen RW. (2004) Susceptibility of cerebellar granule neurons from GM2/GD2 synthase-null mice to apoptosis induced by glutamate excitotoxicity and elevated KCl: rescue by GM1 and LIGA20. Glycoconj J 21(6):305-13.
Xie X, Wu G, Ledeen RW. (2004) C6 cells express a sodium-calcium exchanger/GM1 complex in the nuclear envelope but have no exchanger in the plasma membrane: Comparison to astrocytes. J Neurosci Res 76:363-75.
Xie X, Wu G, Lu ZH, Ledeen RW. (2002) Potentiation of a sodium-calcium exchanger in the nuclear envelope by nuclear GM1 ganglioside. J Neurochem 81(6):1185-95.
Fang Y, Xie X, Ledeen RW, Wu G. (2002) Characterization of cholera toxin B subunit-induced Ca2+ influx in neuroblastoma cells: Evidence for a voltage independent GM1-associated Ca2+ channel. J Neurosci Res 69:669-680.
Wu G, Xie X, Lu ZH, Ledeen RW. (2001) Cerebellar neurons lacking complex gangliosides degenerate in the presence of depolarizing levels of potassium. Proc Natl Acad Sci USA 98:307-312.
Wu G, Lu Z-H, Xie X, Li L, Ledeen RW. (2001) Mutant NG108-15 cells (NG-CR72) deficient in GM1synthase respond aberrantly to axonogenic stimuli and are vulnerable to calcium-induced apoptosis: they are rescued with Liga-20. J Neurochem 76:690-702.
Wu G, Lu Z-H, Xie X, Ledeen RW (2001) Comparison of ganglioside profiles in nuclear and whole cells of NG108-15 and NG-CR72 lines: changes in response to different neuritogenic stimuli. Devl Brain Res 126(2):183-190.
Fang Y, Wu G, Xie X, Lu Z-H, Ledeen RW. (2000) Endogenous GM1 ganglioside of the plasma membrane promotes neuritogenesis by two mechanisms. Neurochem Res 25:931-940.