首页 全所PI名录
  • 张永莲
  • 研究员,中科院院士,博士生导师,上海市分子男科学重点实验室学术委员会主任
  • E-mail: ylzhang@@sibcb.ac.cn
  • 实验室主页: 
    个人简介:
  •   1935年2月20日生于上海市,九三学社社员。1957年9月毕业于上海复旦大学化学系。1957年至今在中国科学院上海生化细胞所进行科研(研究实习员,助理研究员,副研究员,研究员,科学院院士)。从事放射生物学、激素对基因转录调控,近十年来进行精子在附睾中成熟的分子机制研究。1983-1999年间在英国ICRF、美国Chicago大学、Wisconsin大学(Madison)、North Carolina大学、荷兰ERUSMUS大学、澳大利亚Sydney大学等进行合作科研。从1993年至今,先后获得国家自然科学三等奖和二等奖、中科院自然科学一等奖、第二届科技十大女杰、上海市自然科学一等奖和科技功臣和何梁何利生命科学奖等。

    社会任职:
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    研究方向:
  • 精子在附睾中成熟的分子基础
    研究工作:
  • 主要从事雄激素对真核基因转录调控机制研究和睾丸生精过程中及附睾对精子成熟过程中的基因表达程序的调控,现集中在附睾功能基因组研究。该实验室由张友端教授在1978年建立,她于1989年退居二线做顾问后,由其学生张永莲教授担任课题组长。由于这是我国第一个从事这一飞速发展的领域的研究室。因此他们首先建立了各种激素受体的测定方法,并以培训班的形式向全国推广,以填补我国这一领域在研究和临床应用方面的空白。然后进行了雌激素受体的纯化,制备单克隆抗体等基础工作。同时筛选了研究激素作用原理的靶基因系统,通过对大鼠前列腺中PSBP基因表达的时空秩序以及雄激素影响下的特征,证明了它是研究雄激素对真核基因转录的调控机制的一个理想系统。通过对PSBP的C3基因启动子上的顺式调控元件和细胞核中的反式作用因子相互作用的研究,发现了启动子上的一些重要元件如:TATA盒和CCAAT盒上除了有一些通用因子与之作用外,还有组织特异的和雄激素调控相关的因子与之直接或间接地结合然后起协同作用。这些成果获得了1993年的中国科学院的自然科学一等奖,1997年国家自然科学三等奖。为了深入了解多元件,多因子的相互作用中的调控激发程序,该课题组进而开始研究基因转录活性与染色体结构的关系。

    此外,为了将基础研究与生物学重大问题相结合,我们已开始研究睾丸生精过程及附睾对精子成熟过程中的基因表达程序的调控,以期能为男性健康生育调控的药物设计提供新的思路。附睾是一根连接睾丸和输精管的盘曲的细长管道。但不同部位的附睾细胞表达不同的基因,管腔中分泌的种类各异的蛋白质与从睾丸中分化完全的精子相互作用,使精子表面蛋白质的成分得以部分改变或修饰,从而使精子逐步获得运动、获能、精卵结合等能力而成熟,被储存在其尾部等待射精。本组目标是克隆附睾特异表达的基因,建立一个研究精子成熟功能的测试平台去研究这些基因在精子成熟中的作用及其表达调控。这不仅有助于揭示精子在附睾中成熟的分子机理,而且为解决精子成熟异常所引起的不孕症的诊断和治疗和开发一些阻断精子成熟的男性避孕药物研制提供新的药靶和设计思路。
            目前有三方面的工作进行重点开展:
            (1) 附睾特异表达的新蛋白在精子成熟中的功能(条件性knock out/in);
            (2) 附睾特异表达的miRNA在精子成熟中的作用;
            (3) 表观遗传修饰(DNA methylation & histon modification)在附睾和精子成熟中的作用。

    目前正联合所内外力量,优势互补,在此基础上趁胜追击,为我国附睾与精子相关的功能基因组学和男性节育和不育作出更大的供献。实验室已经和国际上的许多实验室有合作课题,遍及美国、英国、澳大利亚和香港地区。目前,课题经费来源国于国家自然科学基金委、中国科学院、上海市科委及美国NIH国际合作项目等。

    承担科研项目情况:
    代表论著:
    1. P. Li, H. C. Chan, B. He, S. C. So, Y. W. Chung, Q. Shang, Y. D. Zhang, and Y. L. Zhang. 2001. An antimicrobial peptide gene found in the male reproductive system of rats. Science. 291(5509): 1783-1785.
    2. Q. Liu, K. G. Hamil, P. Sivashanmugam, G. Grossman, R. Soundararajan, A. J. Rao, R. T. Richardson, Y. L. Zhang, M. G. O’Rand, P. Petrusz, F. S. French, and S. H. Hall. 2001. Primate epididymis-specific proteins: characterization of ESC42, a novel protein containing a trefoil-like motif in monkey and human. Endocrinology. 142(10): 4529-4539.
    3. Y. X. Hu, J. Y. Guo, L. Shen, Y. Chen, Z. C. Zhang, and Y. L. Zhang. 2002. Get effective polyclonal antisera in one month. Cell Res. 12(2): 157-160.
    4. K. G. Hamil, Q. Liu, P. Sivashanmugam, S. Yenugu, R. Soundararajan, G. Grossman, R. T. Richardson, Y. L. Zhang, M. G. O’Rand, P. Petrusz, F. S. French, and S. H. Hall. 2002. Cystatin 11: a new member of the cystatin type 2 family. Endocrinology. 143(7): 2787-2796.
    5. Y. Hu, Z. Zhou, C. Xu, Q. Shang, Y. D. Zhang, and Y. L. Zhang. 2003. Androgen down-regulated and region-specific expression of germ cell nuclear factor in mouse epididymis. Endocrinology. 144(4): 1612-1619.
    6. C. X. Zhou, Y. L. Zhang, L. Xiao, M. Zheng, K. M. Leung, M. Y. Chan, P. S. Lo, L. L. Tsang, H. Y. Wong, L. S. Ho, Y. W. Chung, and H. C. Chan. 2004. An epididymis-specific beta-defensin is important for the initiation of sperm maturation. Nat Cell Biol. 6(5): 458-464.
    7. J. S. Zhang, Q. Liu, Y. M. Li, S. H. Hall, F. S. French, and Y. L. Zhang. 2006. Genome-wide profiling of segmental-regulated transcriptomes in human epididymis using oligo microarray. Mol Cell Endocrinol. 250(1-2): 169-177.
    8. H. X. Yuan, A. H. Liu, L. Zhang, H. Zhou, Y. Wang, H. Zhang, G. Wang, R. Zeng, Y. L. Zhang, and Z. J. Chen. 2006. Proteomic profiling of regionalized proteins in rat epididymis indicates consistency between specialized distribution and protein functions. J Proteome Res. 5(2): 299-307.
    9. H. Diao, C. Y. Guo, D. H. Lin, and Y. L. Zhang. 2007. Intein-mediated expression is an effective approach in the study of beta-defensins. Biochem Biophys Res Commun. 357(4): 840-846.
    10. C. F. Zhu, Q. Liu, L. Zhang, H. X. Yuan, W. Zhen, J. S. Zhang, Z. J. Chen, S. H. Hall, F. S. French, and Y. L. Zhang. 2007. RNase9, an androgen-dependent member of the RNase A family, is specifically expressed in the rat epididymis. Biol Reprod. 76(1): 63-73.
    11. J. Y. Li, H. Y. Wang, J. Liu, Q. Liu, J. S. Zhang, F. C. Wan, F. J. Liu, S. H. Jin, and Y. L. Zhang. 2008. Transcriptome analysis of a cDNA library from adult human epididymis. DNA Res. 15(3): 115-122.
    12. Y. C. Zhou, M. Zheng, Q. X. Shi, L. Zhang, W. Zhen, W. Y. Chen, and Y. L. Zhang. 2008. An epididymis-specific secretory protein HongrES1 critically regulates sperm capacitation and male fertility. PLoS One. 3(12): e4106.
    13. W. Zhen, P. Li, B. He, J. Y. Guo, and Y. L. Zhang. 2009. The novel epididymis-specific beta-galactosidase-like gene Glb1l4 is essential in epididymal development and sperm maturation in rats. Biol Reprod. 80(4): 696-706.
    14. D. M. Cao, Y. Li, R. Yang, Y. Wang, Y. C. Zhou, H. Diao, Y. Zhao, Y. L. Zhang, and J. Lu. 2010. Lipopolysaccharide-induced epididymitis disrupts epididymal beta-defensin expression and inhibits sperm motility in rats. Biol Reprod. 83(6): 1064-1070.
    15. S. G. Hu, G. X. Yao, X. J. Guan, Z. M. Ni, W. B. Ma, E. M. Wilson, F. S. French, Q. Liu, and Y. L. Zhang. 2010. Research resource: Genome-wide mapping of in vivo androgen receptor binding sites in mouse epididymis. Mol Endocrinol. 24(12): 2392-2405.
    16. Y. Zhao, H. Diao, Z. M. Ni, S. G. Hu, H. G. Yu, and Y. L. Zhang. 2011. The epididymis-specific antimicrobial peptide beta-defensin 15 is required for sperm motility and male fertility in the rat (Rattus norvegicus). Cell Mol Life Sci. 68(4): 697-708.
    17. C. M. Wang, C. Y. Huang, Y. H. Gu, Y. C. Zhou, Z. M. Zhu, and Y. L. Zhang. 2011. Biosynthesis and distribution of Lewis X- and Lewis Y-containing glycoproteins in the murine male reproductive system. Glycobiology. 21(2): 225-234.
       
    18. Y. Chen, C. Chu, Y. C. Zhou, Y. F. Ru, H. R. Chen, F. Chen, Q. J. He, Y. L. Zhang, L. L. Zhang and J. L. Shi. 2011. Reversible pore-structure evolution in hollow silica nanocapsules: large pores for siRNA delivery and nanoparticle collecting. Small. 7(20): p. 2935-44.
    19. M. J. Ni, Z. H. Hu, Q. Liu, M. F. Liu, M. H. Lu, J. S. Zhang, L. Zhang and Y. L. Zhang. 2011. Identification and characterization of a novel non-coding RNA involved in sperm maturation. PLoS One. 6(10): e26053.
    20. Y. L. Zhang, J. S. Zhang, Y. C. Zhou, Y. Zhao and M. J. Ni. 2011. Identification of microRNAs and application of RNA interference for gene targeting in vivo in the rat epididymis. J Androl. 32(6): 587-91.
    21. W. B. Ma, S. S. Xie, M. J. Ni, X. X. Huang, S. G. Hu, Q. Liu, A. H. Liu, J. S. Zhang and Y. L. Zhang. 2012. MicroRNA-29a inhibited epididymal epithelial cell proliferation by targeting nuclear autoantigenic sperm protein(NASP). J Biol Chem. 287: 10189-10199.
    22. X. Q. Li, M. J. Ni and Y. L. Zhang. 2012. Detecting miRNAs by liquid hybridization and color development. Methods. 58(2): 151-5.
    23. S. S. Xie, J. Xu, W. B. Ma, Q. Liu, J. X. Han, G. X. Yao, X. X. Huang and Y. L. Zhang. 2013. Lcn5 promoter directs the region-specific expression of cre recombinase in caput epididymidis of transgenic mice. Biology of Reproduction. 88(3): 71.
    24. Y. C. Zhou, Y. F. Ru, C. M. Wang, S. L. Wang, Z. M. Zhou and Y. L. Zhang. 2013. Tripeptidyl peptidase II regulates sperm function by modulating intracellular Ca(2+) stores via the ryanodine receptor. PLoS One. 8(6): e66634.
    25. J. S. Zhang, S. S. Xie, W. B. Ma, Y. Teng, Y. Tian, X. X. Huang and Y. L. Zhang. 2013. A newly identified microRNA, mmu-miR-7578, functions as a negative regulator on inflammatory cytokines tumor necrosis factor-alpha and interleukin-6 via targeting Egr1 in vivo. J Biol Chem. 288(6): 4310-20.
    26. L. Ma, H. G. Yu, Z. M, Ni, S. G. Hu, W. B. Ma, C. Chu, Q. Liu and Y. L. Zhang. 2013. Spink13, an epididymis-specific gene of the Kazal-type serine protease inhibitor (SPINK) family, is essential for the acrosomal integrity and male fertility. J Biol Chem. 288(14): 10154-65.
    27. H. G. Yu, J. Dong, Y. H. Gu, H. Y. Liu, A. J. Xin, H. J. Shi, F. Sun, Y. L. Zhang, D. H. Lin and H. Diao. 2013. The novel human beta-defensin 114 regulates lipopolysaccharide (LPS)-mediated inflammation and protects sperm from motility loss. J Biol Chem. 288(17): 12270-82.
    28. W. B. Ma, S. G. Hu, G. X. Yao, S. S. Xie, M. J. Ni, Q. Liu, X. X. Gao, J. S. Zhang, X. X. Huang and Y. L. Zhang. 2013. An Androgen Receptor-MicroRNA-29a Regulatory Circuitry in Mouse Epididymis. J Biol Chem. 288(41): 29369-81.
    获奖及荣誉:
    研究组成员: