细胞生物学及分子病毒学研究组

 组长:叶昕 博士、研究员

 

 

 

 研究组研究方向

   

  1、流感病毒复制的分子机制及抗病毒天然免疫的调控机理

  2、乙型肝炎病毒调控细胞周期/细胞凋亡及肝癌发生发展的机理

 

  研究组研究内容及意义

     

  1、流感病毒复制的分子机制及抗病毒天然免疫的调控机理

  流感病毒是危害人类健康的重要病原,新发突发流感病毒引起的流感,对人类健康构成极大威胁。流感病毒从侵染宿主细胞,继而在宿主细胞中复制、包装、出芽的整个生命周期,始终依赖于与宿主细胞因子的相互作用,这些宿主细胞因子包括宿主蛋白和非编码RNA。我们前期研究发现流感病毒聚合酶复合体借助宿主细胞转录延伸因子cyclinT1/CDK9, 完成Cap-snatching过程,从而有利于病毒的转录;近年来,随着lncRNA研究的深入,研究者发现lncRNA也参与流感病毒的复制,研究报道长链非编码RNA NRAV是一种抗病毒免疫反应负调控因子,在流感病毒感染过程中明显下调,敲低NRAV则显著抑制流感病毒复制;近期我们的研究揭示长链非编码RNA lnc-ISG20是一种干扰素诱导基因,具有抑制流感病毒复制的作用,并阐释了其作用机制。我们将进一步探究流感病毒与宿主相互作用关系,解析调控病毒感染和复制的重要宿主因子,阐明它们对流感病毒宿主适应性的影响。

  抗病毒天然免疫RLR信号通路的调控对于宿主抗病毒反应和自身稳定性的维持都有着重要的意义,我们前期研究揭示了包括蛋白激酶CK1?1和蛋白磷酸酶Cdc25A在内的多种宿主因子调控RIG-I信号通路的分子机制。我们拟进一步探究抗病毒天然免疫信号通路的调控规律。

 

  乙型肝炎病毒(HBV)是严重影响人类健康的慢性感染性病毒。世界范围内约有2.57亿HBV慢性感染患者,每年约100万患者死于HBV慢性感染导致的肝硬化和肝癌等相关疾病。为了探究HBV相关蛋白和lncRNA在肝癌发生发展中的作用,我们利用RNA深度测序技术比较了HBV阳性和阴性肝癌细胞的转录谱,发现一系列差异表达的蛋白和lncRNAs。我们前期对其中在HBV阳性细胞中上调最为显著的lnc-HUR1展开了深入研究,发现HBV编码的HBx能促进lnc-HUR1的转录;机制研究揭示lnc-HUR1通过结合肿瘤抑制因子p53,抑制p53的转录活性,进而促进细胞增殖和肿瘤的发生发展。我们将深入研究乙型肝炎病毒调控细胞周期/细胞凋亡的机制,揭示乙型肝炎病毒与肝癌发生发展的相关性,为肝癌的诊治提供新的分子靶标。 

 

  2、乙型肝炎病毒调控细胞周期/细胞凋亡及肝癌发生发展的机理

   

 研究组长

 

  研究组长:叶昕 研究员 博士生导师

  电子邮件:yex#im.ac.cn(请将#换为@

  通讯地址:北京市朝阳区北辰西路1号院3号

  邮政编码:100101

 

 

 主要学习及工作经历

   

  1980-1984  厦门大学学士

  1984-1987  中科院上海细胞生物学研究所硕士

  1987-1990  中国医学科学院肿瘤研究所博士

  1990-1992  中科院上海生物化学研究所

  1992-1993  中科院上海生物工程中心副教授

  1994-1995  美国洛克菲勒大学博士后

  1995-1998  美国哥伦比亚大学博士后

  1998-2000  美国伊利诺伊斯大学芝加哥分校资深研究员

  2000-2003  美国贝勒医学院讲师

  2003-2005  美国哈佛医学院讲师

  2005-至今  中科院微生物所研究员、博士生导师

 

 

 获奖情况

    

  2011年和2015年微生物所所长奖教金 

 

 

 研究团队

 

   

 工作人员 

   昕 研究员 

  童晓梅 助理研究员 

  祁丹丹 助理研究员 

 在读研究生 

    芳 (2015-2020 

  李信达 (2015-2020 

   敏 (2017-2020 

  甘利鹏 (2018-2021 

  陈永臣 (2018-2021 

  姚欣丽 (2019-2022 

   勇 (2019-2022 

 客座人员 

  李宇岑 (中国医科大学,2018-2021

  王鸣格 (中国科学技术大学,2019-2022

 已毕业学生 

  李军辉 博   (2006-2009) 

   刚 博    (2006-2009) 

  张军杰 博    (2005-2010) 

   婷 博   (2005-2010) 

   荣 硕   (2007-2010) 

   敏 博   (2006-2011) 

   茜 博   (2006-2011) 

  杜朝阳 博   (2007-2012) 

  孙莉萍 博    (2009-2012) 

  王烨涛 博   (2009-2012) 

  汪世雄 硕   (2009-2012) 

  姜良珍 博   (2008-2013) 

    艳 博  士 (2010-2013) 

  赖文彬 硕  士 (2010-2013) 

    童 硕  士 (2011-2014) 

  刘宁宁 博  士 (2011-2014) 

    磊 硕  士 (2012-2015) 

  张廷虹 博  士 (2012-2015) 

   榛 硕  士 (2013-2016) 

  杨小海 硕  士 (2014-2017) 

  柴文佳 博  士 (2014-2019) 

    琪 博  士 (2014-2019) 

  上官麒麟 硕士 (2016-2019) 

 已离开工作人员 

  张金方 助理研究员 

  王烨涛 助理研究员 

  刘宁宁 助理研究员 

  郭桂杰助理研究员

 

 

 代表性论文

 

  1.Qi Liu, Ningning Liu, Qilin Shangguan, Fang Zhang, Wenjia Chai, Xiaomei Tong, Xin Zhao, Zhiwei Li, Dandan Qi, and Xin Ye, LncRNA SAMD12-AS1 promotes cell proliferation and inhibits apoptosis by interacting with NPM1. Sci Rep. 2019; 9: 11593. 

  2.Xinda Li, Guijie Guo, Min Lu, Wenjia Chai, Yucen Li, Xiaomei Tong, Jing Li, Xiaojuan Jia, Wenjun Liu, Dandan Qi, Xin Ye. Lnc-MxA inhibits IFN-β transcription via forming RNA-DNA triplexes at its promoter. J Virol. 2019, DOI: 10.1128/JVI.00786-19. 

  3.Dandan Qi, Lei Hu, Tong Jiao, Tinghong Zhang, Xiaomei Tong, Xin Ye. Phosphatase Cdc25A negatively regulates antiviral immune response by inhibiting TBK1 activity. J Virol. 92(19):e01118-18, 2018. 

  4.Wenjia Chai, Jing Li, Qilin Shangguan, Qi Liu, Xinda Li, Dandan Qi, Xiaomei Tong, Wenjun Liu, Xin Ye. Lnc-ISG20 inhibits influenza A virus replication by enhancing ISG20 expression. J Virol. 92(16):e00539-18, 2018. 

  5.Ningning Liu, Qi Liu, Xiaohai Yang, Fang Zhang, Xinda Li, Yuanwu Ma, Feifei Guan, Xin Zhao, Zhiwei Li, Lianfeng Zhang, Xin Ye. Hepatitis B virus-upregulated lnc-HUR1 promotes cell proliferation and tumorigenesis by blocking p53 activity. Hepatology. 2018, 68(6):2130-2144., 2018. 

  6.Ningning Liu, Jinfang Zhang , Xiaohai Yang, Tong Jiao, Xin Zhao,Wenxia Li, Jianhua Zhu, Pu Yang, Jianping Jin, Jirun Peng, Zhiwei Li, Xin Ye. HDM2 promotes the NEDDylation of HBV HBx and enhances its stability and functions. J Virol.91, e00340-17, 2017. 

  7.Tinghong Zhang, Zhen Ye, Xiaohai Yang, Yujie Qin,Yi Hu, Xiaomei Tong, Wenbin Lai, Xin Ye. NEDDylation of PB2 Reduces Its Stability and Blocks the Replication of Influenza A Virus. Sci Rep. 7: 43691, 2017. 

  8.Yi Hu, Liangzhen Jiang, Wenbin Lai, Yujie Qing, Tinghong Zhang, Shixiong Wang, Xin Ye. MiR-33a disturbs influenza A virus replication via targeting ARCN1 and inhibiting viral vRNP activity. J Gen Virol. 97(1):27-38, 2016. 

  9.Yan Huang, Liping Sun, Ningning Liu, Qian Wei, Liangzhen JiangXiaomei Tong , Xin Ye. Plk1 up-regulates telomerase activity by affecting hTERT stability telomerase activity by affecting hTERT stability. J Biol Chem. 290:18865-73, 2015. 

  10.Liping Sun, Yan Huang, Qian Wei, Xiaomei Tong, Rong Cai, Grzegorz Nalepa, Xin Ye. Cyclin E-CDK2 Protein Phosphorylates Plant Homeodomain Finger Protein 8 (PHF8) and Regulates Its Function in the Cell Cycle. J Biol Chem. 290, 4075-4085, 2015. 

  11.Ningning Liu, Tong Jiao, Yan Huang, Wenjun Liu, Zhiwei Li, Xin Ye. Hepatitis B Virus Regulates Apoptosis and Tumorigenesis through the MicroRNA-15a-Smad7- Transforming Growth Factor Beta Pathway. J Virol 89, 2739-2749, 2015. 

  12.Yetao Wang, Lei Hu, Xiaomei Tong and  Xin Ye. Casein Kinase 1γ1 Inhibits the RIG-I/TLR Signaling Pathway through Phosphorylating p65 and Promoting Its Degradation.  J Immunol. 192:1855-61, 2014.  

  13.Ningning Liu, Jinfang Zhang, Tong Jiao, Zhiwei Li, Jirun Peng, Qingqing, Cuizhu, Xin Ye. Hepatitis B virus inhibits apoptosis of hepatoma cells by sponging miR-15a/16 cluster. J Virol. 87(24):13370-78, 2013. 

  14.   Zhaoyang Du, Xiaomei Tong, Xin Ye. Cyclin D1 Promotes Cell Cycle Progression through Enhancing NDR1/2 Kinase Activity Independent of Cyclin-dependent Kinase 4. J Biol. Chem. 288(37):26678-87. 

  15.   Qian Wei, Junhui Li, Ting Liu, Xiaomei Tong, Xin Ye. Phosphorylation of minichromosome maintenance protein 7 (MCM7) by cyclin/cyclin-dependent kinase affects its function in cell cycle regulation. J Biol Chem 288: 19715–19725, 2013. 

  16.   Liangzhen Jiang, Yan Huang, Min Deng, Ting Liu, Wenbin Lai, Xin Ye. Polo-Like Kinase 1 Inhibits the Activity of Positive Transcription Elongation Factor of RNA Pol II b (P-TEFb). PLoS ONE 8(8):e72289, 2013. 

  17.   Yetao Wang, Xiaomei Tong, Gang Li, Junhui Li, Min Deng, Xin Ye. Ankrd17 positively regulates RIG-I-like receptor (RLR)-mediated immune signaling. Euro. J Immunol. 42: 1304–1315, 2012. 

  18.   Yetao Wang, Xiaomei Tong, Junjie Zhang, Xin Ye. The complement C1qA enhances RIG-I mediated immune signaling. Immunol. 136:78-85, 2012.  

  19.   Yetao Wang, Xiaomei Tong and Xin Ye. Ndfip1 Negatively Regulates RIG-I- Dependent Immune Signaling by Enhancing E3 Ligase Smurf1-Mediated MAVS Degradation. J Immunol. 189:5304-5313, 2012. 

  20.   Yetao Wang, Xiaomei Tong, Ehimwenma Sheena Omoregie, Wenjun Liu, Songdong Meng, and Xin Ye. Tetraspanin 6 (TSPAN6) Negatively Regulates Retinoic Acid- inducible Gene I-like Receptor-mediated Immune Signaling in a Ubiquitination- dependent Manner. J Biol Chem. 287: 34626–34634, 2012. 

  21.   Junjie Zhang, Ting Liu, Xiaomei Tong, Gang Li, Jinghua Yan, Xin Ye. Identification of novel virus inhibitors by influenza A virus specific reporter cell based screening. Antiviral Res.93:48-54, 2011. 

  22.   Ting Liu, Min Deng, Junhui Li, Xiaomei Tong, Qian Wei and Xin Ye. Phosphorylation of Right Open Reading Frame 2 (Rio2) Protein Kinase by Polo-like Kinase 1 Regulates Mitotic Progression. J Biol. Chem. 286: 36352-36360, 2011. 

  23.   Junhui Li, Min Deng, Qian Wei, Ting Liu, Xiaomei Tong and Xin Ye. Phosphorylation of MCM3 Protein by Cyclin E/Cyclin- dependent Kinase 2 (Cdk2) Protein Regulates Its Function in Cell Cycle. J Biol. Chem. 286:39776-85, 2011. 

  24.   Junjie Zhang , Gang Li, Xin Ye. Cyclin T1/CDK9 Interacts with Influenza A Virus Polymerase and Facilitates Its Association with Cellular RNA Polymerase II. J Virol. 84(24):12619-12627, 2010. 

  25.   Gang Li, Junjie Zhang, Xiaomei Tong, Wenjun Liu, Xin Ye. Heat shock protein 70 inhibits the activity of influenza a virus ribonucleoprotein and blocks the replication of virus in vitro and in vivo. PLoS ONE 6 (2): e16546, 2010.                                   

  26.   Min Deng, Fahui Li, Bryan A Ballif, Shan Li, Xi Chen, Lin Guo, Xin Ye. Identification and functional analysis of a novel cyclin E/CDK2 substrate Ankrd17. J Biol. Chem. 284:7875-7888, 2009. 

  27.   Junjie Zhang, Gang Li, Xiaoling Liu, Zengfu Wang, Wenjun Liu, Xin Ye, Influenza A virus M1 blocks the classical complement pathway through interacting with C1qA. J Gen. Virol. 90:2751-2758, 2009. 

  28.   Yali ChenHuijuan GuoZhaoyang DuXingzhong  LiuYongsheng Che, Xin Ye. Ecology-based screen identifies new metabolites from a Cordyceps-colonizing fungus as cancer cell proliferation inhibitors and apoptosis inducers.  Cell Prolif.  42:838-847, 2009. 

    

  

 专利 

 

  1.  叶昕;张立新;秦玉洁;刘雪婷;叶榛;张敬宇,化合物AJ-4在制备治疗或预防抗流感病毒药物中的应用,专利授权号:ZL201510644254.1,授权日期: 2019.01.15 

  2.  叶昕;张立新;叶榛;代焕琴;秦玉洁,化合物ID45在制备治疗或预防流感病毒药物中的应用,专利授权号:ZL201510359166.7, 授权日期:2019.01.15 

  3.  叶昕;张立新;秦玉洁;刘雪婷;叶榛;张敬宇,化合物AJ-2在制备治疗或预防抗流感病毒药物中的应用,专利授权号:ZL201510644234.4,授权日期:2019.02.12 

  4. 叶昕;张军杰;刘婷;童晓梅;李刚,含有A型流感特异性启动子的重组细胞及其应用,专利授权号:ZL201010532889.X,授权日期: 2012.12.19