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个人信息

博士生导师
研究员

Email: yandong@sibs.ac.cn
个人网页:

研究方向

RNA修饰介导的发育与代谢研究

严冬

个人简介

1996-2000 南京大学,基础学科教学强化部,理学学士

2002-2009 美国辛辛那提大学医学院,分子与发育生物学博士

2010-2016 哈佛大学医学院遗传学系,博士后

2016.08-至今  中国科学院上海生命科学研究院植物生理生态研究所,研究员

2017年获上海市浦江人才计划资助。

在国外期间获得Damon Runyon Cancer ResearchCharles A. King和美国心脏协会等基金资助。目前承担国家自然科学基金面上项目 (2)、重大研究计划培育项目,科技部重点研发计划,及中国科学院等项目

研究工作

RNA 中有超过 100 种化学修饰被发现,它们的生物学功能和调控机制才刚刚开始被揭示,因此这些科学问题成为目前国际研究的焦点并形成了一个新的领域,表观转录组学 (epitranscriptomics)。围绕RNA表观修饰在动物发育与代谢中的调控作用,我们实验室将聚焦于以下几个研究方向:(1) 筛选 m6A 通路中新的因子及果蝇性别决定途径新的成员;(2) 解析m6A修饰在发育和代谢过程中的作用机理;(3) 构建在动物体内修改RNA修饰的体系;(4) 利用在 m6A 研究过程 中积累的技术和手段展开对其它 RNA 修饰的功能性探索。

主要成果

1. N6-甲基腺嘌呤 (m6A) 是真核生物mRNA中最常见的内部修饰,在干细胞分化、动植物发育、和人类疾病中起着关键的作用。我们实验室前期首次鉴定了m6A甲基转移酶复合物 (又称为writer complex) 两个新的、在进化中保守的组分 Nito/Rbm15 Xio/ZC3H13,并发现它们通过调控果蝇性别决定关键基因 Sxl 的可变剪接 (alternative splicing) 来控制果蝇的性别决定 (PNAS, 2018)

 

2. 筛选并鉴定果蝇性别决定通路两个新的基因NitoXio。从摩尔根时代开始,对果蝇性别决定的研究已有超过 90 年的历史。在这一过程中,只有10个基因被发现具有转变性别的能力,因此找到这一通路新的基因具有非常重要的生物学意义。通过全基因组RNAi筛选发现新的性别决定基因Nito (Developmental Cell, 2014PNAS, 2015),并进一步使用蛋白互作网络发现并命名了新的性别决定基因Xio

 

3. 揭示形态素浓度梯度形成的分子机制。形态素 (morphogen) 是发育生物学中的一个重要概念,它是指一类信号分子被分泌出去以后形成浓度梯度,而浓度的高低决定了周围细胞的分化。揭示硫酸肝素蛋白多糖家族成员在信号分子 WntHedgehogFGF的传输过程中发挥关键作用 (Developmental Cell, 2009; Development, 2010, 2005; Developmental Biology, 2007; Nature Cell Biology, 2008综述; Cold Spring Harbor Perspectives in Biology, 2009综述)

     

    1.    Silver, J., Wirtz-Peitz, F., Simoes, S., Pellikka, M., Yan, D., Binari, R., Nishimura, T., Li, Y., Harris T., Perrimon, N. and Tepass U. (2019) Apical polarity proteins recruit the RhoGEF Cysts to promote junctional myosin assembly. The Journal of Cell Biology, doi: 10.1083/jcb.201807106.

    2.    Guo, J., Tang, H., Li, J., Perrimon, N.* and Yan, D.* (2018) Xio is a novel component of the Drosophila sex determination pathway and RNA N6-methyladenosine methyltransferase complex. PNAS, 115(14):3674-3679.

    3.    Li, Z., You, L., Yan, D., James, A. Huang, Y. and Tan A. (2018) Bombyx mori histone methyltransferase BmAsh2 is essential for silkworm piRNA-mediated sex determination. PLoS Genetics, 14(2), e1007245.

    4.    Kan, L., Grozhik, A., Vedanayagam, J., Patil, D., Pang, N., Lim, K., Huang, Y., Joseph, B., Lin, C., Despic, V., Guo, J., Yan, D., Kondo, S., Deng, W., Dedon, P., Jaffrey, S. and Lai, E. (2017) The m6A pathway facilitates sex determination in Drosophila. Nature Communications, 8:15737.

    5.    Yan, D. and Perrimon, N. (2015) Spenito is required for sex determination in Drosophila melangaster. PNAS, 112(37):11606-11611.

    6.    Sun, J., Wei, H., Xu, J., Chang, J., Yang, Z., Ren, X., Lv, W., Liu, L., Pan, L., Wang, X., Qiao, H., Zhu, B., Ji, J., Yan, D., Xie, T., Sun, F. and Ni, J. (2015) Histone H1-Mediated Epigenetic Regulation Controls Germline Stem Cell Self-Renewal by Modulating the Acetylation of H4 Lysine 16. Nature Communications, 6:8856.

    7.    Perkins, L., Holderbaum, L., Tao, R., Hu, Y., Sopko, R., McCall, K., Yang-Zhou, D., Flockhart, I., Binari, R., Shim, H., Miller, A., Housden, A., Foos, M., Randklev, S., Kelley, C., Namgyal, P., Villalta, C., Liu, L., Jiang, X., Huan-Huan, Q., Xia, W., Fujiyama, A., Toyoda, A, Ayers, K., Blum, A., Czech, B., Neumuller, R., Yan, D., Cavallaro, A., Hibbard, K., Hall, D., Cooley, L., Hannon, G., Lehmann, R., Parks, A., Mohr, S., Ueda, R., Kondo, S., Ni, J. and Perrimon, N. (2015) The Transgenic RNAi Project at Harvard Medical School: Resources and Validation. Genetics, 201(3):843-52.

    8.    Zeng, X., Han, L., Singh S., Liu, H., Neumüller, R., Yan, D., Hu, Y., Liu, Y., Liu W., Lin, X. and Hou, S. (2015) Genome-Wide RNAi Screen Identifies Networks Involved in Intestinal Stem Cell Regulation in Drosophila. Cell Reports, 10(7): 1226-1238.

    9.    Droujinine I., Yan, D. and Perrimon, N. (2014) A sharp end to sugary Wingless travels. The Journal of Cell Biology. 206(7):819-821(Comment).

    10. Yan, D., Neumuller, R., Buckner, M., Ayers, K., Li, H., Hu, Y., Yang-Zhou, D., Pan, L., Wang, X., Kelley, C., Vinayagam, A., Binari, R., Randklev, S., Perkins, L., Xie, T., Cooley, L. and Perrimon, N. (2014) A regulatory network of Drosophila germline stem cell self-renewal. Developmental Cell, 28(4): 459-473.

    11. Staller, M., Yan, D., Randklev, S., Bragdon, M., Wunderlich, Z., Tao, R., Perkins, L., DePace, A. and Perrimon, N. (2013) Depleting Gene Activities in Early Drosophila Embryos with the “Maternal-Gal4–shRNA” System. Genetics, 193(1): 51-61.

    12. Friedman, A., Tucker, G., Singh, R., Yan, D., Arunachalam, V., Hu, Y., Binari, R., Hong, P., Sun, X., Porto, M., Pacifico, S., Murali, T., Finley, R., Asara, J., Berger, B. and Perrimon, N. (2011) Proteomic and functional genomic landscape of receptor tyrosine kinase and Ras/ERK signaling. Science Signaling, 4, rs10.

    13. Yan, D., Wu, Y., Yang, Y., Belenkaya, T., Tang, X. and Lin, X. (2010) The cell-surface proteins Dally-like and Ihog differentially regulate Hh signaling strength and range during development. Development, 137, 2033-2044.

    14. Yan, D., Wu, Y., Feng, Y., Lin, S. and Lin, X. (2009) The core protein of glypican Dally-like determines its biphasic activity in Wingless morphogen signaling. Developmental Cell, 17(4): 470-481.

    15. Yan, D and Lin, X. (2009) Shaping morphogen gradient by proteoglycans. In “Generation and Interpretation of Morphogen Gradients”, Cold Spring Harbor Laboratory Press (book chapter).

    16. Yan, D and Lin, X. (2008) Opposing roles for glypicans in Hedgehog signalling. Nature Cell Biology, 10(7):761-3 (news and views).

    17. Belenkaya, T., Wu, Y., Tang, X., Zhou, B., Cheng, L., Sharma, Y., Yan, D., Selva, E. and Lin, X. (2008) The Retromer Complex Influences Wnt Secretion by Recycling Wntless from Endosomes to the Trans-Golgi Network. Developmental Cell, 14(1): 120-131.

    18. Yan, D. and Lin, X. (2007) Drosophila glypican Dally-like acts in FGF-receiving cells to modulate FGF signaling during tracheal morphogenesis. Developmental Biology, 312(1):203-16.

    19. Han, C. #, Yan, D. #, Belenkaya, T. and Lin, X. (2005) Drosophila Glypicans Dally and Dally-like shape the extracellular Wingless morphogen gradient in the wing disc. Development, 132, 667-679.

    20. Tao, Q., Yokota, C., Puck, H., Kofron, M., Birsoy, B., Yan, D., Asashima, M., Wylie.C.C, Lin, X. and Heasman, J. (2005) Maternal Wnt11 activates the canonical Wnt signaling pathway required for axis formation in Xenopus embryos. Cell, 120(6): 857-871.

    21. Belenkaya, T., Han, C., Yan, D., Opoka, R.J., Khodoun, M., Liu, H. and Lin, X. (2004) Drosophila Dpp morphogen movement is independent of dynamin-mediated endocytosis and is controlled by glypican members of heparan sulfate proteoglycans. Cell, 119(2): 231-44.

    22. Yang, L., Yan, D., Bruggeman, M., Du, H. and Yan, C. (2004) Mutation of a lysine residue in a homeodomain generates dominant negative thyroid transcription factor 1. Biochemistry, 43(39),12489-97.

    23. Yang, L., Yan, D., Yan, C. and Du, H. (2003) Peroxisome proliferator-activated receptor gamma and ligands inhibit surfactant protein B gene expression in the lung. The Journal of Biological Chemistry, 278, 36841-36847.

    24. Yang, L., Naltner, A., Kreiner, A., Yan, D., Cowen, A., Du, H. and Yan, C. (2003) An enhancer region determines hSP-B gene expression in bronchiolar and ATII epithelial cells in transgenic mice. American Journal of Physiology Lung Cellular and Molecular Physiology, 284(3): L481-8.

     

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