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受体与心血管疾病研究室
发布日期:2015-08-31浏览次数: 字号:[ ]

 

 

  

  研究室PI:张幼怡 博士 教授 博士生导师

  prof. YouYi Zhang

  Phone:010-82802306

  E-mail:zhangyy@bjmu.edu.cn

  

  

  教育及培训经历

  1999-2000  美国埃默里大学药理系, 博士后(科研培训)

  1992-1993  北京医科大学第三医院血管医学研究所, 博士后, 研究工作为受体

  药理与病理生理

  1989-1992  新疆医学院医疗系心血管内科与日本大学医学部第二内科联合培养

  博士生, 获医学博士学位

  1985-1988  新疆医学院医疗系心血管内科硕士研究生, 获医学硕士学位

  1977-1982  新疆医学院医疗系, 获医学学士学位

  工作经历

  2014.5 — 现在  北京大学医学部心血管研究所 所长

  2014.4 — 现在  北京大学前沿交叉学科研究院 副院长

  2012.5 — 现在  心血管受体研究北京市重点实验室 主任

  2011.2 — 现在 卫生部心血管分子生物学与调节肽重点实验室 副主任

  2006.4 — 2014.4北京大学前沿交叉科学研究院生物医学跨学科中心副主任

  2004.6 — 2014.4  北京大学医学部心血管研究所 所长(共同)

  2002.5 — 现在 分子心血管学教育部重点实验室(北京大学) 副主任

  2001.8 — 现在  北京大学第三医院血管医学研究所, 研究员,副所长

  1993.12 — 2001.7  北京医科大学第三医院血管医学研究所, 副研究员

  1988.8 —1988.12  新疆医学院第一附属医院心内科,主治医师

  1982.12 —1985.8  新疆医学院第一附属医院心内科,住院医师

  

  社会兼职

  中国病理生理学会秘书长、中国病理生理学会受体专业委员会主任委员、中国病理生理学会心血管专业委员会副主任委员、中国药理学会心血管药理专业委员会副主任委员。《中国科学:生命科学》常务编委,《生理学报》、《中国病理生理学杂志》、《中国药学杂志》,《中华医学杂志(英文版)》等编委。

  

  研究经历

  长期从事肾上腺素受体与心血管疾病发病机制的研究,主要研究肾上腺素受体在心血管系统的分布、信号转导、生理功能及在病理状态下的改变以及受体之间的交互作用。提出肾上腺素受体非经典信号通路在介导心脏炎症、心脏肥厚和心肌纤维化中发挥重要作用,对多种亚型肾上腺素受体及其信号转导机制在心血管共存的生理与病理意义进行了系统的研究。研究心衰早期钙离子调控与转运机制,揭示了心肌肥厚演变到心衰的分子耦联特征,为心衰的早期诊治提供了理论依据。利用单分子检测技术,发现肾上腺素受体在细胞内的"step by step"转运模式,提出alpha1肾上腺素受体激动后在细胞内转运过程中也特异性传递信号。发现心肌细胞与邻近细胞新"通道"-- 膜纳米管,为心脏细胞间信号通讯和物质交换提出了全新路径。

  作为负责人先后承担国家科技部重点基础研究发展规划项目“973”课题、国家自然科学基金重大国际合作项目、重点项目和面上项目、北京市自然科学基金,等13项基金。共发表学术论文200余篇,其中SCI112篇。2001 年获国家教委中国高校自然科学一等奖(第2 完成人)。参与编写《动态心电图》、《分子核医学》、《受体信号转导系统与疾病》和《生命科学中的单分子行为及细胞内实时检测》等著作。

  

  研究室成员:

  李子健   研究员

  吕志珍   主任技师

  宋峣  助理研究员

  肖晗   助理研究员

  

  研究室研究方向:

  1. 多种亚型肾上腺素受体在心血管共存的生理与病理意义;

  2. 心血管重塑的网络调控及早期防治的基础研究;

  3. 肾上腺素受体单个分子在活细胞中的动态行为;

  4. 心力衰竭的分子机制与转化医学。

  

  近年发表文章代表作:

  1. Wei Feng, Yao Song, Chao Chen, Zhi Zhen Lu, Youyi Zhang.  Stimulation of Adenosine A2B Receptors Induces Interleukin-6 Secretion in Cardiac Fibroblasts via PKC-δ-P38 signaling pathway. British Journal of Pharmacology, 2010, 159:1598-1607 ( with COMMENTARY  159, 1595–1597)

  2.  高炜,秦雷,熊春阳,方竞,张幼怡. 基底刚度对新生大鼠心脏成纤维细胞增殖和粘附的影响. 中国分子心脏病学杂志, 2010, 10 (2): 97-102.

  3.  Qi JY, Xu M, Lu ZZ, Zhang YY. 14-3-3 inhibits insulin-like growth factor-I-induced proliferation of cardiac fibroblasts via a phosphatidylinositol 3-kinase-dependent pathway. Clin Exp Pharmacol Physiol, 2010, 37: 296-302.

  4.  He K, Luo W, Zhang Y, Liu F, Liu D, Xu L, Qin L, Xiong C, Lu Z, Fang X, Zhang Y. Intercellular Transportation of Quantum Dots Mediated by Membrane Nanotubes. ACS Nano, 2010, 4 (6), 3015–3022.

  5.  Xiao H, Ma X, Feng W, Fu Y, Lu Z, Xu M, Shen Q, Zhu Y, Zhang Y. Metformin attenuates cardiac fibrosis by inhibiting the TGFb1-smad3 signalling pathway. Cardiovasc Res , 2010: 87, 504–513

  6.  Jiang SY, Xu M, Ma XW, Xiao H, Zhang YY.  Distinct AMPK phosphorylation site characterizes cardiac hypertrophy induced by L-thyroxine and angiotensinII. Clin Exp Pharmacol Physiol, 2010:37;919–925.

  7.  Xiao H, Zhang YY, Du XJ, Lu ZZ. Developmental changes in the geometry, function and responsiveness of the mouse heart to b-adrenergic stimulation as determined by high-resolution echocardiography. Clin Exp Pharmacol Physiol. 2010;37:826-832.

  8.   Liu X, Gai Y, Liu F, Gao W, Zhang Y, Xu M, Li Z. Trimetazidine inhibits pressure overload-induced cardiac fibrosis through NADPH oxidase-ROS-CTGF pathway. Cardiovasc Res. 2010;88:150-158  

  9.        Zhao X, Nan Y, Xiao C, Zheng J, Zheng X*, Wei Y, Zhang Y*. Screening the bioactive compounds in aqueous extract of Coptidis rhizoma which specifically bind to rabbit lung tissues  b2-adrenoceptor using an affinity chromatographic selection method . J Chromatogr B Analyt Technol Biomed Life Sci. 2010 Jul 15;878(22):2029-34

  10.    冯伟, 张幼怡。 MicroRNA基因及其靶位点的单核苷酸多态性与疾病易感性。生理科学进展,2010,41(6):443-445.

  11.    He K*, Fu Y*, Zhang W, Yuan J, Li Z, Lv Z, Zhang Y*, Fang X*. Single-molecule imaging revealed enhanced dimerization of transforming growth factor β type Ⅱ receptors in hypertrophic cardiomyocytes. Biochem Biophys Res Commun. 2011;407(2):313-7.

  12.    Ma X, Song Y, Chen C, Fu Y, Shen Q, Li Z, Zhang Y.* Distinct actions of intermittent and sustained b-adrenoceptor stimulation on cardiac remodeling.  Sci China Life Sci. 2011;54(6):493-501

  13.    Shi X*, Qin L*, Zhang X, He K, Xiong C, Fang J, Fang X*, Zhang Y*. Elasticity of cardiac cells on the polymer substrates with different stiffness: an atomic force microscopy study. Phys Chem Chem Phys. 2011;13(16):7540-5

  14.    Fu YN*, Xiao H*, Ma XW, Jiang SY, Xu M, Zhang YY*.  Metformin attenuates pressure overload-induced cardiac hypertrophy via AMPK activation.  Acta Pharmacol Sin. 2011;32(7):879-87.

  15.    Liu F, He K, Yang X, Xu N, Liang Z, Xu M, Zhao XS, Han QD, zhang YY*.  a1A-Adrenergic receptor induces activation of extracellular signal-regulated kinase 1/2 through endocytic pathway. PLoS ONE 2011;6(6): e21520.

  16.     He K, Shi X, Zhang X, Ma X, Liu F, Xu M, Lv Z, Fang X*, Zhang Y*. Long-distance intercellular connectivity between cardiomyocytes and cardiofibroblasts mediated by membrane nanotubes. Cardiovasc Res.  2011; 92, 39–47. doi: 10.1093/cvr/cvr189 ( with editorial  92, 5–6)

  17.    Li ZJ, Liu N, Han QD, Zhang YY*. A proteome reference map and regulation network of the neonatal rat cardiomyocyte. Acta Pharmacologica Sinica, 2011; 32(9):1116-27;

  18.    Lin S*, Li S* , Chen Z , He X, Zhang Y, Xu X, Xu M2*, Yuan G *  Formation, recognition and bioactivities of a novel G-quadruplex in the STAT3 gene. Bioorganic & Medicinal Chemistry Letters 2011:21; 5987–5991.

  19.    Li Y, Zhang H, Liao W, Song Y, Ma X, Chen C, Lü Z, Li Z, Zhang Y*. Transactivated EGFR mediates α1-AR-induced STAT3 activation and cardiac hypertrophy. Am J Physiol Heart Circ Physiol. 2011;301(5):H1941-51

  20.    Chen Z, Huang C, Yang YL, Ou-Yang HQ, Zhang YY, Xu M*. Inhibition of the STAT3 signaling pathway is involved in the antitumor activity of cepharanthine in SaOS2 cells. Acta Pharmacol Sin, 2012, 33: 101-108.(IF1.953)

  21.    Chen C, Du JH, Feng W, Song Y, Lu ZZ, Xu M, Li ZJ, Zhang YY*. b-Adrenergic receptors stimulate interleukin-6 production through Epac-dependent activation of PKCd/p38 MAPK signalling in neonatal mouse cardiac fibroblasts. Br J Pharmacol, 2012, 166: 676-688.((IF4.409)

  22.    Zhao XF, Lu HY, Huang J, Zheng JB, Zheng XH*, Zhang YY*. Binding Interaction Between Prazosin and Immobilized Receptor by Frontal Analysis. Chromatographia, 2012, 75:411-415. (IF1.19)

  23.    Fu YN, Xiao H, Zhang YY *. β-adrenoceptor signaling pathways mediate cardiac pathological remodeling. Front Biosci (Elite Ed),2012 Jan 1, 4:1625-37. Review (IF3.52)

  24.    Lin S, Gu H,Xu M*, Cui X, Zhang Y, Gao W, Yuan G* .The formation and stabilization of a novel G-quadruplex in the 5'-flanking region of the relaxin gene. PLoS One. 2012;7(2):e31201. Epub 2012 Feb 21. (IF4.092)

  25.    Hao-Di Wu*, Ming Xu*?1, Rong-Chang Li*1, Liang Guo*1, Ying-Si Lai1, Shi-Ming Xu1,Su-Fang Li1, Quan-Long Lü1, Lin-Lin Li1, Hai-Bo Zhang2, You-Yi Zhang1, Chuan-Mao Zhang1, Shi-Qiang Wang?1 Ultrastructural Remodeling of Ca2+ Signaling Apparatus in Failing Heart Cells.Cardiovasc Res. 2012, 95(4):430-8. Epub 2012 Jun 15. (IF6.064)

  26.    Xu M, Wu HD, Li RC, Zhang HB, Wang M, Tao J, Feng XH, Guo YB, Li SF, Lai ST, Zhou P, Li LL, Yang HQ, Luo GZ, Bai Y, Xi JJ, Gao W, Han QD, Zhang YY, Wang XJ, Meng X, Wang SQ.Mir-24 regulates junctophilin-2 expression in cardiomyocytes. Circ Res. 2012 Sep 14;111(7):837-41. Epub 2012 Aug 13.(IF9.489)

  27.    Gu HP, Lin S, Xu M*, Yu HY, Du XJ, Zhang YY, Yuan G, Gao W* Up-Regulating Relaxin Expression by G-Quadruplex Interactive Ligand to Achieve Antifibrotic Action.  Endocrinology. 2012 Aug;153(8):3692-700. Epub 2012 Jun 6(IF4.459)

  28.    Zhao X, Li Q, Bian L, Zheng X*, Zheng J, Zhang Y*, Li Z. Using immobilized G-protein coupled receptors to screen bioactive traditional Chinese medicine compounds with multiple targets. J Pharm Biomed Anal. 2012 Nov;70:549-52. doi: 10.1016/j.jpba.2012.05.004. Epub 2012 May 15

  29.    Li SF, Liu F, Liu W, Zhao Y, Lu ZZ, Xu M*, Zhang YY. Bioactivity of indolylpiperiding-piperazine derivatives on a1-adrenoceptor-mediated inotropic responsse. Chin J Pharmacol Taxicol, 中国药理学与毒理学杂志Jun2012, 26(3): 276-281

  30.    Wang J, Song Y, Zhang Y, Xiao H, Sun Q, Hou N, Guo S, Wang Y, Fan K, Zhan D, Zha L, Cao Y, Li Z, Cheng X, Zhang Y, Yang X*. Cardiomyocyte overexpression of miR-27b induces cardiac hypertrophy and dysfunction in mice. Cell Res. 2012 Mar;22(3):516-27. doi: 10.1038/cr.2011.132. Epub 2011 Aug 16 (第二作者单位)(IF 8.19)

  31.    Niu LM, Liang Y,Xu M, Zhang YY, Zhang Y, He B*.Effect of polymorphisms in the β2-adrenergic receptor on the susceptibility and pulmonary function of patients with chronic obstructive pulmonary disease: a meta analysis. Chin Med J (Engl). 2012 Jun;125(12):2213-8.

  32.    Xiao H, Zhang Y Y. Cutting edge advances in nanomedicine. Sci China Life Sci, 2012, 55: 1–2, doi: 10.1007/s11427-012-4391-y (IF2.03)

  33.    沈 蔷,陈 莉1,3 李 昊2,3 马晓伟2,4 张幼怡2,3,4* 苦味酸- 天狼猩红染色和MASSON 染色评价心脏纤维化的比较.中国分子心脏病学杂志 2012; 12(2) :118-120

  34.    MA Ding, ZHANG You-yi, GUO Yan-li, LI Zi-jian* and GENG Li*. Profiling of microRNA-mRNA reveals roles for miRNAs in cervical cancer. Chinese Medical Journal. 2012;

  35.    Yao Song#, Jialin Xu#, Yanfeng Li, Chunshi Jia, Xiaowei Ma, Lei Zhang, Xiaojie Xie, Yong Zhang, Xiang Gao, Youyi Zhang*, Dahai Zhu*. Cardiac ankyrin repeat protein attenuates cardiac hypertrophy by inhibition of ERK1/2 and TGF-b signaling pathways. PLoS ONE, PLoS One. 2012;7(12):e50436. doi: 10.1371/journal.pone.0050436. Epub 2012 Dec 5

  36.    Xueyan Wang,ab Xue Meng,ab Weijing Pei,ad Zijian Li,c Youyi Zhang,*c Jianbin Zhengb and Xiaohui Zheng*ab. Construction of adrenergic receptor subtype affinity chromatographic models for detection of ligand–receptor interactions. Anal. Methods, 2012, 4, 3420–3424

  37.    肖晗, 张幼怡*. G蛋白偶联受体的探索之路——记2012 年诺贝尔化学奖得主Robert J. Lefkowitz 和Brian K.Kobilka. 中国科学: 生命科学. 2012: 42(12); 1018-1024

  38.    Pan B, Ren H, Lv X, Zhao Y, Yu B, He Y, Ma Y, Niu C, Kong J, Yu F, Sun WB, Zhang Y, Willard B, Zheng L. Hypochlorite-induced oxidative stress elevates the capability of HDL in promoting breast cancer metastasis.J Transl Med. 2012 Mar 30;10:65

  39.    Liu D, Ji L, Zhang D, Tong X, Pan B, Liu P, Zhang Y, Huang Y, Su J, Willard B, Zheng L. Nonenzymatic glycation of high-density lipoprotein impairs its anti-inflammatory effects in innate immunity.Diabetes Metab Res Rev. 2012 Feb;28(2):186-95. doi: 10.1002/dmrr.1297.

  40.    Pan B, Ren H, Ma Y, Liu D, Yu B, Ji L, Pan L, Li J, Yang L, Lv X, Shen X, Chen B, Zhang Y, Willard B, He Y, Zheng L. High-density lipoprotein of patients with type 2 diabetes mellitus elevates the capability of promoting migration and invasion of breast cancer cells. Int J Cancer. 2012 Jul 1;131(1):70-82. doi: 10.1002/ijc.26341. Epub 2011 Aug 30.

  41.    Pan B, Ren H, He Y, Lv X, Ma Y, Li J, Huang L, Yu B, Kong J, Niu C, Zhang Y, Sun WB, Zheng L.HDL of patients with type 2 diabetes mellitus elevates the capability of promoting breast cancer metastasis. Clin Cancer Res. 2012 Mar 1;18(5):1246-56. Epub 2012 Jan 18.

  42.    Wang Y, Zhao B, Zhang Y, Tang Z, Shen Q, Zhang Y, Zhang W, Du J, Chien S, Wang N. Krüppel-like factor 4 is induced by rapamycin and mediates the anti-proliferative effect of rapamycin in rat carotid arteries after balloon injury. Br J Pharmacol. 2012 Apr;165(7):2378-88. doi: 10.1111/j.1476-5381.2011.01734.x.(合作)

  43.    Zhao X, Li Q, Bian L, Zheng X*, Zheng J, Zhang Y*, Li Z. Using immobilized G-protein coupled receptors to screen bioactive traditional Chinese medicine compounds with multiple targets. J Pharm Biomed Anal. 2012 Nov;70:549-52. doi: 10.1016/j.jpba.2012.05.004. Epub 2012 May 15

  44.    Zhang HB, Li RC, Xu M, Xu SM, Lai YS, Wu HD, Xie XJ, Gao W, Ye H, Zhang YY, Meng X, Wang SQ. Ultrastructural Uncoupling between T-tubules and Sarcoplasmic Reticulum in Human Heart Failure. Cardiovasc Res. 2013 May 1;98(2):269-76.

  45.    Li RC, Tao J, Guo YB, Wu HD, Liu RF, Bai Y, Lv ZZ, Luo GZ, Li LL, Wang M, Yang HQ, Gao W, Han QD, Zhang YY, Wang XJ, Xu M*, Wang SQ. In Vivo Suppression of MiR-24 Prevents the Transition toward Decompensated Hypertrophy in Aortic-constricted Mice. Circ Res. 2013; 112: 601-605. Epub 2013 Jan 13.

  46.    Zhao N, Yu H, Yu H, Sun M, Zhang YY, Xu M*, Gao W. MiRNA-711-SP1-collagen-I pathway is involved in the anti-fibrotic effect of pioglitazone in myocardial infarction. Sci China Life Sci. 2013 May;56(5):431-9.

  47.    Zongshi Li#, Yao Song#, Rui Xing, Haiyi Yu, Youyi Zhang,Zijian Li*, Wei Gao*.Heat Shock Protein 70 Acts as a Potential Biomarker for Early Diagnosis of Heart Failure. PLoS ONE, 2013,8(7):e67964.

  48.    邢瑞,杨承志,吴济民,鲁海燕,吕志珍,张幼怡,李子健*. HIP-55抑制异丙基肾上腺素诱导的心脏成纤维细胞ROS产生. 中国分子心脏病学杂志,2013,2,424-428.

  49.    Zhao Xin-feng, Huang Jing-jing, Li Qian, Wei Lu-sha, Zheng Jian-bin, Zheng Xiao-hui*, Li Zi-jianc and Zhang You-yi*. Revealing binding interaction between seven drugs and immobilized b2-adrenoceptor by high-performance affinity chromatography using frontal analysis. J. Mol. Recognit. 2013; 26: 252–257.

  

  




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