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生物化学与分子生物学系

余佳

课题组简介

本课题组由张俊武研究员建立于1993年,承担过国家七.五、863、基础研究重大前期专项、973、重大科学计划、美国中华医学基金(CMB)、国家自然科学基金重大项目和面上项目等,过去近二十年重点研究珠蛋白基因表达调控、造血相关基因功能及机制及老年性痴呆(AD)相关基因,已毕业博士33人,硕士6人。共发表论文130多篇(SCI 44篇)。2012年,余佳研究员接任课题组长,现有工作人员包括:余佳(研究员)、 张俊武(研究员)、马艳妮(副研究员)、王小爽(助理研究员)、赵华路(副主任技师)、高玉风(助理研究员)、司艳敏(技术员)及博士后2人(任悦、张娴勰),在读博士研究生10人,硕士研究生8人,联合培养博士后2人。课题组近十年以RNA和干细胞生物学为主要研究方向,试图以RNA和转录后调控为突破口,研究干细胞和造血细胞的谱系分化、扩增和再生,以期为细胞治疗和成分输血提供理论基础和新方向。通过多年努力,课题组建立了完善的胚胎干细胞和造血干细胞培养体系、RNA实验体系、组学平台及生物信息学团队,并与国内外多个领域内一流实验室建立了紧密合作关系、共享研究资源、共同培养研究生与博士后。课题组既有丰富的历史沉淀,又年轻而朝气蓬勃,学术气氛积极向上,致力于成为“严谨、求实、快乐、奋进”的研究团队。欢迎各位有志于科学研究、对干细胞及RNA生物学感兴趣的考生报考。


    博士,研究员,博士生导师,课题组长

    国家杰出青年科学基金获得者

    医学分子生物学国家重点实验室

    中国医学科学院基础医学研究所&北京协和医学院基础学院

    E-mail: j-yu@ibms.apfhnbc.com; yujia_new@msn.com

 个人简介

余佳,男,1978年生,研究员,博士生导师,RNA与干细胞生物学研究组组长,医学分子生物学国家重点实验室PI,国家杰出青年科学基金获得者(2017,生命科学部),长江学者奖励计划入选者(2017),北京协和医学院首批长聘教授(2018),中国医学科学院RNA与造血调控研究重点实验室主任。2006年7月毕业于中国医学科学院/北京协和医学院基础医学研究所生化与分子生物学系,理学博士。2006-2007年在美国伊利诺伊大学芝加哥分校工作(Post-doc)。2007-2009年在美国西北大学Feinberg医学院工作(Post-doc)。2009年10月回国加入中国医学科学院基础医学研究所生化系及医学分子生物学国家重点实验室。作为负责人承担国家自然科学基金委重大研究计划、重点项目及面上项目等;作为负责人承担科技部973子课题、国家重点研发计划及国家重大研究计划。余佳博士同时担任中国医学科学院-以色列Weizmann研究所联合实验室PI,中国医学科学院“医学与健康科技创新工程”创新团队项目首席科学家,人血细胞分子图谱(ABC)研究联盟首批倡议及参加成员。余佳实验室主要兴趣集中在造血调控、谱系分化及再生,综合运用干细胞培养及基因操纵等体外实验,造血干细胞移植、基因敲除小鼠及谱系示踪等体内技术,结合多种单细胞组学及计算生物学手段,研究RNA及其互作蛋白质在干细胞中的功能和调控机理。近五年作为通讯作者在Cell Stem CellEMBO JournalNature CommunicationsCell ResearchCancer ResearchNucleic Acids ResearchAutophagyOncogeneMCB等国际学术期刊上发表SCI论文20余篇,被引用1900余次,也作为主要作者在Nature MedicineBloodElife等学术期刊发表多篇论文。目前担任北京市生化协会理事、青委会主任;全国血液生理专业委员会理事;全国实验血液学会青委会副主任,担任Blood, Nucleic Acids Research, Oncogene, Cancer Research, MCB, JBC等杂志特邀审稿人。

研究方向 

RNA和干细胞生物学

研究工作简介

       RNA生物学是系统认识和研究各种RNA的生物发生、分子特征、生物学功能和分子机理的一门学科,也是生命科学的新兴学科。过去二十年里,这一学科得到长足发展,特别是新一代测序技术的出现不但帮助发现了更多编码RNA的特征,而且鉴定了多种非编码RNA分子,是目前国际上最前沿的领域之一。干细胞生物学毫无疑问也是目前国际上最前沿和挑战最大的领域之一。阐明干细胞自我更新和分化的分子调控机理可为再生医学和癌症治疗提供重要支撑。以RNA为切入点研究干细胞生物学具有独特优势:i. 以往被视为遗传信息传递中间站的messenger RNA (mRNA)其实具有远超我们所理解的转录后调控方式,如RNA编辑、RNA修饰、RNA稳定性调节、RNA选择性剪接及RNA选择性加帽或加尾等,这些方式均会引起相应的基因表达变化,从而最终改变遗传信息从DNA向蛋白质的共线性传递。特别是近期关于RNA修饰的研究已经渐渐衍生出RNA表观遗传学这一研究方向;ii. RNA组学,特别是单细胞RNA组学的发展,使我们可以精确描绘发育层级的分子动力学图谱,从而推动了目前中国、美国及欧洲的人类细胞图谱计划;iii. ENCODE计划最重要的贡献之一:非编码RNA的大量发现,更是大大扩充了我们人类对于自身,乃至各个物种的基本遗传和进化认知。但该计划也提出了未来多个重要的挑战,即各种各样的非编码RNA的分子特征是什么,是否具有重要的生物学功能,又有那些独特的分子调控机制?

       课题组主要以胚胎干细胞向中胚层分化、血管内皮-造血转换、胚胎/成体造血干细胞分化为模型,综合运用单细胞测序技术,干细胞培养及基因操纵等体外实验,造血干细胞移植、基因敲除小鼠及谱系示踪等体内技术,结合多种组学和计算生物学手段,研究RNA及其互作蛋白质分子在干细胞中的功能和调控机理。

 

课题组近期主攻下列科学问题:
1、通过单细胞泛转录组(mRNA、RNA选择性剪接、RNA编辑和长非编码RNA)描绘造血干细胞起源、谱系命运和分化成熟的分子动力学图谱;

2、非编码RNA加工与成熟的分子机制及其在干细胞分化与相关疾病中的功能机理;
3、胚胎干细胞退出全能性及定向中胚层分化的分子机理;
4、造血干细胞异质性的表观遗传调控机理。

 

研究成果简介

        我们实验室过去五年主要以成体造血干细胞谱系分化、胚胎干细胞向中胚层定向分化及消化道癌症为研究模型或对象,鉴定其中起重要作用的非编码RNA及其互作蛋白质并研究它们的作用机理,取得了一系列重要成果:

  1. 利用单细胞测序技术绘制出造血干细胞发育全程的LncRNA图谱,并揭示调控“内皮-造血”转换的关键lncRNA及其表观遗传调控机理Cell Stem Cell, 2019
  2. 利用转录组测序技术揭示造血干细胞向粒系/单核系分化命运选择中的自噬分子表型(Autophagy, 2018
  3. 揭示RNA结合蛋白QKI5调控造血干细胞向红细胞分化Cell Research, 2017),RNA结合蛋白KSRP调控造血干细胞向粒系/单核系分化命运选择 Nat. Commun., 2017);
  4. 利用单细胞测序技术绘制出造血干细胞发育过程mRNA分子表达谱并证明自噬相关分子在造血干细胞发育中存在阶段特异性表达及重要功能Autophagy, 2017);
  5. 解决了自微小RNA发现以来的一个重要科学问题即微小RNA初级转录本茎环结构远端序列是否具有调节功能?证明茎环远端序列存在功能性RNA模体,并且这些RNA模体可通过RNA结合蛋白和RNA高级结构介导参与微小RNA加工Cell Research, 2017);基于该理论进一步通过生物信息学手段建立了蛋白质-RNA互作事件数据库Raid 2.0 (Nucl. Acids Res, 2017)。
  6. 鉴定了胚胎干细胞定向中胚层分化的关键微小RNA基因簇并发现其“表型弹性”现象和产生机理 (The EMBO J. 2015);
  7. 鉴定了成体造血干细胞向髓系分化的关键微小RNA基因/基因簇 (Blood, 2012Cell Death&Differentiation, 2014);
  8. 揭示微小RNA与红系分化关键转录因子间的多重互作机制 (Nucl. Acids Res, 2013, 2014; Mol. Cel. Biol, 2013);发现RISC复合物成员Ago2介导的微小间"cross talk"是红系分化的重要分子事件(Cell Research, 2011);
  9. 鉴定了多个可用于急性髓系白血病诊治的微小RNA靶标(Oncogene, 2015, 2016; PLoS Genetics, 2016);
  10. 鉴定了多个消化道癌症发生相关的微小RNA并阐明其致癌机理 (Cancer Research, 2010; J Hepatol, 2010; Carcinogenesis, 2014; Cancer Research, 2015; Gastric Cancer, 2015; Sci Rep, 2016);
  11. 发现RNA结合蛋白及长非编码RNA可以调控髓系分化及胃癌发生(Mol. Cel. Biol, 2015; Sci Rep, 2015; JECCR, 2015)。

在研项目:

  1. 国家杰出青年科学基金,2017-2021、造血细胞发育调控、主持。
  2. 科技部国家重点研发计划干细胞及转化专项,2016-2020、造血干细胞的发育规律及调控机制、参与。
  3. 国家自然科学基金重点项目,2016-2020、长链非编码RNA在造血髓系链系呈递及分化发育中的功能及机制研究、主持。
  4. 科技部重大科学研究计划,2015-2019、长非编码RNA在精子发生中的功能及机制、课题负责人。
  5. 中国医学科学院“医学与健康科技创新工程”创新团队项目,2017-2020、造血干细胞异质性的表观遗传调控机理、首席科学家。
  6. 中国医学科学院“医学与健康科技创新工程”重大协同创新项目,2017-2020、人类血细胞图谱计划、参与(负责人类红细胞图谱)。

代表性论著 (? first author; * corresponding author):

  1. Dong L?, Zhang Z?, Xu J, Wang F, Ma Y, Li F, Shen C, Liu Z, Zhang J, Liu C*, Yi P*, Yu J*. Consistency analysis of microRNA-arm expression reveals microRNA-369-5p/3p as tumor suppressors in gastric cancer. Mol Oncol. 2019 Jul;13(7):1605-1620
  2. Zhengyi Zhang?, Jingnan Pi?, Dongling Zou?, Xiaoshuang Wang?, Jiayue Xu?, Shan Yu, Ting Zhang, Feng Li, Hualu Zhao, Fang Wang, Dong Wang*, Yanni Ma*, Jia Yu*. microRNA arm-imbalance partially from targets-mediated decay promotes gastric cancer progression. Nature Communications. In Press
  3. Jie Zhou?, Jiayue Xu?, Lingling Zhang?, Siqi Liu?, Yanni Ma?, Xin Wen, Junkai Hao, Zongcheng Li, Yanli Ni, Xianlong Li, Fan Zhou, Qingqing Li, Fang Wang, Xiaoshuang Wang, Yanmin Si, Pengcheng Zhang, Chen Liu, Marisa Bartolomei, Fuchou Tang, Bing Liu*, Jia Yu*, and Yu Lan*. Combined Single-Cell Profiling of lncRNAs and Functional Screening Reveals that H19 Is Pivotal for Embryonic Hematopoietic Stem Cell Development. Cell Stem Cell. 2019 Feb 7. 24; 285-298
  4. Lintao Zhao, Ran He, Haixia Long, Bo Guo, Qingzhu Jia, Diyuan Qin, Si-Qi Liu, Zhongyu Wang, Tong Xiang, Jue Zhang, Yulong Tan, Jiani Huang, Junying Chen, Fang Wang, Minglu Xiao, Jianbao Gao, Xinxin Yang, Hao Zeng, Xinxin Wang, Chunyan Hu, Peter B. Alexander, Alistair L. J. Symonds, Jia Yu, Yisong Wan, Qi-Jing Li, Lilin Ye, Bo Zhu. Late-stage tumors induce anemia and immunosuppressive extramedullary erythroid progenitor cells. Nature Medicine. 2018. 24, 15361544 
  5. Weiqian Li, Yue Ren, Yanmin Si, Fang Wang*, Jia Yu*. Long non-coding RNAs in hematopoietic regulation. Cell Regen (London). 2018 Oct 11;7(2):27-32. (Review)
  6. Hongmei Zhao?, Xiaoshuang Wang?, Ping Yi?, Yanmin Si, Puwen Tan, Jinrong He, Shan Yu, Yue Ren, Yanni Ma, Junwu Zhang, Dong Wang*, Fang Wang*, Jia Yu*. KSRP specifies monocytic and granulocytic differentiation through regulating miR-129 biogenesis and RUNX1 expression. Nature Communications. 2017. 8 1428
  7. Fang Wang?, Wei Song?, Hongmei Zhao?, Yanni Ma, Yuxia Li, Di Zhai, JingnanPi, Yanmin Si, Jiayue Xu, Lei Dong, Rui Su, Mengmeng Zhang, Yong Zhu, Xiaoxia Ren, Fei Miao, Wenjie Liu, Feng Li, Junwu Zhang, Aibin He, Ge Shan, Jingyi Hui,  Linfang Wang, Jia Yu*. The RNA-binding protein QKI5 regulates primary miR-124-1 processing via a distal RNA motif during erythropoiesis. Cell Research. 2017 Mar; 27(3):416-439
  8. Yongfei Hu, Yan Huang, Ying Yi, Hongwei Wang, Bing Liu*, Jia Yu*, Dong Wang*. Single-cell RNA sequencing highlights transcription activity of autophagy-related genes during hematopoietic stem cell formation in mouse embryos. Autophagy. 2017 Apr 3;13(4):770-771
  9. Ying Yi, Yue Zhao, Chunhua Li, Lin Zhang, Huiying Huang, Yana Li, LanlanLiu, Ping Hou, Tianyu Cui, Puwen Tan, Yongfei Hu, Ting Zhang, Yan Huang, Xiaobo Li*, Jia Yu*, Dong Wang*. RAID v2.0: an updated resource of RNA-associated interactions across organisms. Nucleic Acids Research. 2017 Jan 4;45(D1):D115-D118
  10. Shanshan Ai, Yong Peng, Chen Li, Fei Gu, Xianhong Yu, Yanzhu Yue, Qing Ma, Jinghai Chen, Zhiqiang Lin, Pingzhu Zhou, Huafeng Xie, Terence W Prendiville, Wen Zheng, Yuli Liu, Stuart H Orkin, Da-Zhi Wang, Jia Yu, William T Pu, Aibin He. EED orchestration of heart maturation through interaction with HDACs is H3K27me3-independent. Elife. 2017;6
  11. Rui Su?, Lei Dong?, Dongling Zou, Hongmei Zhao, Yue Ren, Feng Li, Ping Yi, Lanfang Li, Yong Zhu, Yanni Ma, Jing Wang, Fang Wang*, Jia Yu*. MicroRNA-23a, -27a and -24 synergistically regulate JAK1/Stat3 cascade and serve as novel therapeutic targets in human acute erythroid leukemia. Oncogene. 2016 Nov 17;35 (46):6001-6014
  12. Yanni Ma?, Nan Yao?, Guang Liu?, Lei Dong, Fang Wang, Bin Wang, He Dong, Xueju Wei, Meili Zhang, Shaowei Ji, Yufang Liu, Junwu Zhang, Yangming Wang, Yue Huang*, Jia Yu*. Functional screen reveals essential roles of miR-27a/24 in differentiation of embryonic stem cell. The EMBO Journal. 2015. 34(3):361378
  13. Yuxuan Wang?, Changzheng Liu?, Min Luo?, Zhengyi Zhang?, Jianan Gong, Jingjing Li, Lei Dong, Haishuang Lin, Yanni Ma, Fang Wang, Yi Wang, Jie Chen, Junwu Zhang, Hongyan Jia, Yan Kong, Jia Yu*. Chemotherapeutic drugs induced miR-29s-cateninδ signaling suppresses metastasis in gastric cancer. Cancer Research. 2015 April 1. 75(7):1332-44
  14. Wei Song, Wenjie Liu, Hong Zhao, Shangze Li, Xin Guan, Jianming Ying, Yefan Zhang, Fei Miao, Mengmeng Zhang, Xiaoxia Ren, Xiaolu Li, Fan Wu, Yuechao Zhao, Yuanyuan Tian, Wenming Wu, Jun Fu, Junbo Liang, Wei Wu, Changzheng Liu, Jia Yu, Shudong Zong, Shiying Miao, Xiaodong Zhang, Linfang Wang. Rhomboid domain containing 1 promotes colorectal cancer growth through activation of the EGFR signaling pathway. Nature Communications. 2015 Aug 24;6:8022
  15. Zheng Li, Huizi Lei, Min Luo, Yi Wang, Lei Dong, Yanni Ma, Changzheng Liu, Wei Song, Fang Wang, Junwu Zhang, Jianxiong Shen*, Jia Yu*. DNA methylation downregulated mir-10b acts as a tumor suppressor in gastric cancer. Gastric Cancer. 2015 Jan;18(1):43-54. (Cited by 119)
  16. Fang Wang?, Yong Zhu?, Lihua Guo?, Lei Dong, Huiwen Liu, Haixin Yin, Zhongzu Zhang, Y Li, Changzheng Liu, Yanni Ma, Wei Song, Aibin He, Qiang Wang, Linfang Wang, Junwu Zhang, Jianxiong Li, Jia Yu*. A regulatory circuit comprising GATA1/2 switch and microRNA-27a/24 promotes erythropoiesis. Nucleic Acids Research. 2014 Jan;42(1):442-457
  17. Jianan Gong?, Jianxiong Li?, Yi Wang?, Changzheng Liu?, Hongyan Jia, Chongliang Jiang, Yuxuan Wang, Min Luo, Hongmei Zhao, Lei Dong ,Wei Song, Fang Wang, Weibin Wang, Junwu Zhang*, Jia Yu*. Characterization of miR-29 family expression and investigation of their mechanistic roles in gastric cancer. Carcinogenesis. 2014. 35 (2):497-506. (Cited by 37)
  18. Jianan Gong?, Jia Yu?, Haishuang Lin?, Xinhua Zhang, Xiaolin Yin, Zhen Xiao, Fang Wang, Xiaoshuang Wang, Rui Su, Chao Shen, Hualu Zhao, Yanni Ma and Junwu Zhang. The role, mechanism and potentially therapeutic application of microRNA-29 family in acute myeloid leukemia. Cell Death & Differentiation. (2014) 21, 100-112
  19. Yong Zhu?, Dongsheng Wang?, Fang Wang?, Tingting Li, Lei Dong, Huiwen Liu, Yanni Ma, Fengbing Jiang, Haixin Yin, Wenting Yan, Ming Luo, Z Tang, Guoyuan Zhang, Qiang Wang, Junwu Zhang, Jingguo Zhou, Jia Yu*. A comprehensive analysis of GATA-1-regulated miRNAs reveals miR-23a to be a positive modulator of erythropoiesis. Nucleic Acids Research. 2013. Apr; 41(7):4129-43
  20. Yanni Ma?, Bin Wang?, Fengbing Jiang?, Dongsheng Wang?, Huiwen Liu, Yunmeng Yan, He Dong, Fang Wang, Bei Gong, Yong Zhu, Lei Dong, Haixin Yin, Zhongzu Zhang, Hualu Zhao, Zhikui Wu, Junwu Zhang, Jingguo Zhou, Jia Yu, Jia Yu*. A Feedback Loop Consisting of MicroRNA 23a/27a and the Beta-Like Globin Suppressors KLF3 and SP1 Regulates Globin Gene Expression. Molecular and Cellular Biology. 2013 Oct; 33(20):3994-4007
  21. Jia Yu*, Fang Wang. Recent progress in microRNA study: Benefits from technique advance. SCIENCE CHINA Life Sciences. July 2012. 55 (7): 649-650. (Invited comment)
  22. Xiaoshuang Wang?, Jianan Gong?, Jia Yu, Fang Wang, Xinhua Zhang, Xiaolin Yin, Zhenqing Tan, Zimian Luo, Guihua Yang, Chao Shen, Junwu Zhang. MicroRNA-29a and microRNA-142-3p are regulators of myeloid differentiation and acute myeloid leukemia. Blood. 2012 May 24;119(21):4992-5004. (Cited by 90)
  23. Fang Wang, Jia Yu, Guihua Yang, Xiaoshuang Wang , Junwu Zhang. Regulation of erythroid differentiation by miR-376a and its targets. Cell Research. 2011 Aug;21(8): 1196-209. (Cited by 23)
  24. Shuangni Yu, Zhaohui Lu, Changzheng Liu, Yunxiao Meng, Yihui Ma, Wugan Zhao, Jianping Liu, Jia Yu*, Jie Chen *. MiRNA-96 suppresses KRAS and functions as a tumor suppressor gene in pancreatic cancer. Cancer Research. 2010 Jul 15;70(14):6015-25. (Cited by 201)
  25. Changzheng Liu?, Jia Yu?, Shuangni Yu, Robert M.Lavker, Lei Cai, Wei Liu, Kegong Yang, Xiaodong He, Songsen Chen. MicroRNA-21 acts as an oncomir through multiple targets in human hepatocellular carcinoma. Journal of Hepatology. 2010 Jul;53(1):98-107. doi: 10.1016/j.jhep.2010.02.021. (Cover story, Cited by 111)
  26. Jia Yu?, Han Peng?, Qing Ruan, Anees Fatima, Spiro Getsios, and Robert M. Lavker. MicroRNA-205 promotes keratinocyte migration via the lipidphosphatase SHIP2.The FASEB Journal. 2010 Oct;24(10):3950-9. (Cited by 68)
  27. Robert M. Lavker, Jia Yu and David G Ryan. The Tiny World of MicroRNAsin the Cross Hairs of the Mammalian Eye. Human Genomics. 2009. 3(4): 332-348 (Review)
  28. Jia Yu?, David G. Ryan?, Spiro Getsios, Michelle Oliveira-Fernandes, Anees Fatima, and Robert M. Lavker. MicroRNA-184 antagonizes microRNA-205 to maintain SHIP2 levels in epithelia. Proceedings of the National Academy of Sciences of the USA. 2008 Dec 9;105(49):19300-5. (Cited by 177)

Books:
1. MicroRNA研究方法与应用.中国协和医科大学出版社. 2008. (副主编)
2. MicroRNA鉴定与功能分析技术.化学工业出版社.2012. (主编)

 


   张 俊 武

    博士,研究员

    电话:010-69156423;010-65105098

    E-mail: junwu_zhang@apfhnbc.com


个人简介

男,1946年9月出生。1970年北京大学生化专业本科毕业后留校作助教。1979年入中国医学科学院基础医学研究所做研究生,1982年获硕士学位后留所。1985-88及1991-92在美国Univ. of Washington医学遗传专业和Markey分子医学中心做senior fellow。1993年为医学分子生物学国家重点实验室研究员,1994年获博导资格。研究过地中海贫血等遗传病基因诊断、老年性痴呆相关基因、低氧应答机制和珠蛋白基因表达调控。近几年重点研究与髓系细胞分化和急性髓系白血病相关的蛋白质基因和非编码RNA的功能机制及表达调控。共发表论文160余篇(SCI 77篇,SCI引用千余次)。曾获3项国家科技进步奖(二等1项,三等2项,第2或3完成人)及8项部级成果奖(一等1项,二等7项,5项为第1或2完成人)。主编论著1部(血红蛋白与血红蛋白病),参编10部。多年作为研究生《基因分子生物学》和《医学分子生物学》课程主讲之一。1998年被评为国家突出贡献中青年专家,2001年获政府特殊津贴。

代表性论著 (? first author; * corresponding author):

  1. Li Song, Haishuang Lin, Jianan Gong, Hua Han, Xiaoshuang Wang, Rui Su, Mingtai Chen, Chao Shen, Yanni Ma, Jia Yu, Junwu Zhang*. microRNA-451-modulated hnRNP A1 takes a part in granulocytic differentiation regulation and acute myeloid leukemia. Oncotarget. 8(33):55453-55466. 2017
  2. Rui Su, Jianan Gong, Mingtai Chen, Li Song, Chao Shen, Xinhua Zhang, Xiaolin Yin, Hongmei Ning, Bing Liu, Fang Wang, Yanni Ma, Hualu Zhao, Jia Yu, Junwu Zhang*. c-Myc suppresses miR-451?YWTAZ/AKT axis via recruiting HDAC3 in acute myeloid leukemia. Oncotarget. 7(47):77430-77443. 2016
  3. Chao Shen, Ming-Tai Chen, Xin-Hua Zhang, Xiao-Lin Yin, Hong-Mei Ning, Rui Su, Hai-Shuang Lin, Li Song, Fang Wang, Yan-Ni Ma, Hua-Lu Zhao, Jia Yu, Jun-Wu Zhang*. The PU.1-Modulated MicroRNA-22 Is a Regulator of Monocyte/Macrophage Differentiation and Acute Myeloid Leukemia. PLoS Genet. 2016 Sep 12;12(9):e1006259.
  4. Yin H, Song P, Su R, Yang G, Dong L, Luo M, Wang B, Gong B, Liu C, Song W, Wang F, Ma Y, Zhang J, Wang W, Yu J. DNA Methylation mediated down-regulating of MicroRNA-33b and its role in gastric cancer. Sci Rep. 2016 Jan 5;6:18824.
  5. Ming-Tai Chen, Lei Dong, Xin-Hua Zhang, Xiao-Lin Yin, Hong-Mei Ning, Chao Shen, Rui Su, Feng Li , Li Song, Yan-Ni Ma, Fang Wang Hua-Lu Zhao1, Jia Yu, Jun-Wu Zhang*, ZFP36L1 promotes monocyte/macrophage differentiation by repressing CDK6, Sci Rep, 5:16229/DOI:19.1038/srep16229, 2015 (November 6)
  6. Ming-Tai Chen, Hai-Shuang Lin, Chao Shen, Yan-Ni Ma, Fang Wang, Hua-Lu Zhao, Jia Yu, Jun-Wu Zhang*, The PU.1-regulated long noncoding RNA lnc-MC Controls human monocyte/macrophage differentiation through interaction with microRNA-199a-5p, Mol Cell Biol 3518:3212-3224, 2015
  7. Rui Su, Hai-Shuang Lin, Xin-Hua Zhang, Xiao-Lin Yin, Hong-Mei Ning, Bing Liu, Peng-Fei Zhai, Jia-Nan Gong, Chao Shen, Li Song, Jing Chen, Fang Wang, Hua-Lu Zhao, Yan-Ni Ma, Jia Yu, Jun-Wu Zhang*, MiR-181 family: Regulators of myeloid differentiation and acute myeloid leukemia as well as potential therapeutic targets, Oncogene 34(25):3226-3239, 2015
  8. Hai-Shuang Lin, Jia-Nan Gong, Rui Su, Ming-Tai Chen, Li Song, Chao-Shen, Fang, Yan-Ni Ma, Hua-Lu Zhao, Jia Yu, Wei-Wei Li, Li-Xia Huang, Xin-Hua Xu, Jun-Wu Zhang*, MiR-199a-5p inhibits monocyte/macrophage differentiation by targeting activin A type 1B receptor gene and finally reducing C/EBPα expression, J Leukocyte Biol, 96(6): 1023-1035, 2014
  9. Peng-Fei Zhai, Fang Wang, Rui Su, Hai-Shuang Lin, Chong-Liang Jiang, Gui-Hua Yang, Jia Yu, Jun-Wu Zhang*, The regulatory roles of miR-146b and its target platelet-derived growth factor receptor alpha (PDGFRA) in erythropoiesis and megakaryocytopoiesis, J Biol Chem, 289: 22600-22613, doi: 10.1074/jbc.M114.547380, 2014
  10. Jia-Nan Gong, Jia Yu, Hai-Shuang Lin, Xin-Hua Zhang, Xiao-Lin Yin, Zhen Xiao, Fang Wang, Xiao-Shuang Wang, Rui Su, Chao Shen, Hua-Lu Zhao, Yan-Ni Ma, Jun-Wu Zhang*, The role, mechanism and potentially therapeutic application of MicroRNA-29 family in acute myeloid leukemia, Cell Death Differ, 21(1): 100-112, 2014
  11. Jianan Gong, Jianxiong Li, Yi Wang, Changzheng Liu, Hongyan Jia, Chongliang Jiang, Yuxuan Wang, Min Luo, Hongmei Zhao, Lei Dong, Fang Wang, Weibin Wang, Junwu Zhang*, Jia Yu*. Characterization of microRNA-29 family expression and investigation of their mechanistic roles in gastric cancer. Carcinogenesis, 35(2): 497-506, 2014
  12. Xiao-Shuang Wang, Jia-Nan Gong, Jia Yu, Fang Wang, Xin-Hua Zhang, Xiao-Lin Yin, Zhen-Qing Tan, Zi-Mian Luo, Gui-Hua Yang, Chao Shen, Jun-Wu Zhang*, MicroRNA-29a and microRNA-142-3p are regulators in myeloid differentiation and actual myeloid leukemia, Blood 119(21):4992-5004,2012
  13. Guo-Min Shen, Ying-Ze Zhao, Ming-Tai Chen, Feng-Lin Zhang, Xiao-Ling Liu, Yi Wang, Chang-Zheng Liu, Jia Yu Jun-Wu Zhang*, Hypoxia inducible factor (HIF1) promotes LDL and VLDL uptake through inducing VLDLR under hypoxia, Biochemistry J 441(2):675-683, 2012
  14. Feng-Lin Zhang, Guo-Min Shen, Xiao-Ling Liu, Fang Wang, Ying-Ze Zhao, Jun-Wu Zhang*, Hypoxia-inducible factor 1-mediated human GATA1 induction promotes erythroid differentiation under hypoxic conditions, J Cell Mol Med 16(8):1889-1899, 2012
  15. Xiaobo Li, Junwu Zhang, Lin Gao, Caitlin Gordon, Thomas Butler, Laurie B. Owen, Yaguang Xi, MIR-181 mediates cell differentiation by interrupting the lin28 and let-7 feedback circuit, Cell Death Differ, 19(3):378-386, 2012
  16. Feng-Lin Zhang, Guo-Min Shen, Xiao-Ling Liu, Fang Wang, Ying-Ze Zhao, Jun-Wu Zhang*, Hypoxia-inducible factor 1-mediated human GATA1 induction promotes erythroid differentiation under hypoxic conditions, accepted, J Cell Mol Med, 2011 (DOI: 10.1111/j.1582-4934.2011.041484.x)
  17. Xiu-Hua Bi, Cui-Min Lu, Qian Liu, Zhen-Xin Zhang, Hua-Lu Zhao, Jia Yu, Jun-Wu Zhang*, A 14 bp indel variation in the NCX1 gene modulates the age at onset in late-onset Alzheimers disease, J Neurol Transm, 119:383-386,2012
  18. Fang Wang, Jia Yu, Gui-Hua Yang, Xiao-Shuang Wang, Jun-Wu Zhang*, MicroRNA-376a regulates erythropoiesis by targeting CDK2 and AGO2, Cell Res 21(8):1196-209, 2011
  19. Xiao-Bo Li, Jing Chen, Min-Jie Deng, Fang Wang , Zhan-Wen Du, Jun-Wu Zhang*, Zinc finger protein HZF1 (ZNF16) promotes K562 cell proliferation by interacting with and inhibiting INCA1, Mol Med Rep 4(6):1131-7, 2011
  20. Hai-Chuan Yu, Hua-Lu Zhao, Zhi-Kui Wu, Jun-Wu Zhang*, Eos Negatively Regulates Human γ-globin Gene Transcription During Erythroid Differentiation, Plos One, 6(7):e22904:1-12, 2011
  21. Zhang JW?, Song W-F, Zhao YJ, Wu GY, Qiu ZM,Wang FN, Chen SS, Stamatoyannopoulos G, Molecular characterization of a novel form of (Agdb)°-thalassemia deletion in a Chinese family. Blood 81:1624-9, 1993
  22. Zhang JW?, Stamatoyannopoulos G, Anagnoun NP, Laotian (δβ)0-thalassemia:molecular characterization of novel deletion associated with increased production of fetal hemoglobin. Blood 72:983-8, 1988



   马 艳 妮

    博士,副研究员,硕士生导师

    2015年度院校“协和新星”,2017年度北京市“科技新星”

    电话:010-65105098

    E-mail: yanni_ma@126.commayanni@ibms.cams.cn

 个人简介

马艳妮,女,1981年11月出生,副研究员,硕士生导师。2008年7月毕业于中国医学科学院基础医学研究所生化与分子生物学系,理学博士。2008-2011年于中国科学院生物物理研究所任助理研究员。2011年7月加入中国医学科学院基础医学研究所生化与分子生物学系,医学分子生物学国家重点实验室工作。作为负责人承担国家自然科学基金委青年基金项目、面上项目,作为科研骨干参与科技部973项目,国家重点研发计划。获北京市“科技新星”(2017)、“协和新星” ”(2015)等人才计划支持。作为第一作者或通讯作者(含共同)Cell Stem CellEMBO J、Nature CommunicationMol Cell Bio等国际学术期刊上发表SCI论文10篇。以共作者在Cell Res、Oncogene、NAR、Cancer Res、Cell Death&Differ等国际学术期刊上发表SCI论文17篇。

目前研究方向为非编码RNA及RNA结合蛋白在多能干细胞分化、红细胞发育成熟、珠蛋白基因表达调控中的功能机制研究。

代表性论著 (? first author; * corresponding author):

  1. Jie Zhou?, Jiayue Xu?, Lingling Zhang?, Siqi Liu?, Yanni Ma?, Xin Wen, Junkai Hao, Zongcheng Li, Yanli Ni, Xianlong Li, Fan Zhou, Qingqing Li, Fang Wang, Xiaoshuang Wang, Yanmin Si, Pengcheng Zhang, Chen Liu, Marisa Bartolomei, Fuchou Tang, Bing Liu*, Jia Yu*, and Yu Lan*. Combined Single-Cell Profiling of lncRNAs and Functional Screening Reveals that H19 Is Pivotal for Embryonic Hematopoietic Stem Cell Development. Cell Stem Cell. 2019 Feb 7. 24; 285-298
  2. Ma Y?, Yao N?, Liu G?, Dong L, Liu Y, Zhang M, Wang F, Wang B, Wei X, Dong H, Wang L, Ji S, Zhang J, Wang Y, Huang Y*, Yu J*. Functional screen reveals essential roles of miR-27a/24 in differentiation of embryonic stem cells. EMBO J. 2015 Feb 3;34(3):361-78
  3. Zhengyi Zhang?, Jingnan Pi?, Dongling Zou?, Xiaoshuang Wang?, Jiayue Xu?, Shan Yu, Ting Zhang, Feng Li, Hualu Zhao, Fang Wang, Dong Wang*, Yanni Ma*, Jia Yu*. microRNA arm-imbalance partially from targets-mediated decay promotes gastric cancer progression. Nature Communications. In Press
  4. Ma Y?, Wang B?, Jiang F?, Wang D?, Liu H, Yan Y, Dong H, Wang F, Gong B, Zhu Y, Dong L, Yin H, Zhang Z, Zhao H, Wu Z, Zhang J, Zhou J*, Yu J*. A feedback loop consisting of microRNA-23a/27a and the β-like globin suppressors KLF3 and SP1 regulates globin gene expression. Mol Cell Biol. 2013, 33(20):3994-4007
  5. Fang Wang?, Wei Song?, Hongmei Zhao?, Yanni Ma, Yuxia Li, Di Zhai, JingnanPi, Yanmin Si, Jiayue Xu, Lei Dong, Rui Su, Mengmeng Zhang, Yong Zhu, Xiaoxia Ren, Fei Miao, Wenjie Liu, Feng Li, Junwu Zhang, Aibin He, Ge Shan, Jingyi Hui, Linfang Wang, Jia Yu. The RNA-binding protein QKI5 regulates primary miR-124-1 processing via a distal RNA motif during erythropoiesis. Cell Research. 2017 Mar; 27(3):416-439
  6. Weibin Wang?, Lijun Zhao?, Xueju Wei, Lanlan Wang, Siqi Liu, Yu Yang, Fang Wang, Guotao Sun, Junwu Zhang, Yanni Ma*, Yupei Zhao*, Jia Yu*. MicroRNA-320a promotes 5-FU resistance in human pancreatic cancer cells. Scientific Reports. 2016 Jun 9;6:27641
  7. Wei X, Wang W, Wang L, Zhang Y, Zhang X, Chen M, Wang F, Yu J, Ma Y*, Sun G*. MicroRNA-21 induces 5-fluorouracil resistance in human pancreatic cancer cells by regulating PTEN and PDCD4. Cancer Med. 2016 Feb 10. doi: 10.1002/cam4.626
  8. Ma YN?, Chen MT?, Wu ZK, Zhao HL, Yu HC, Yu J, Zhang JW. Emodin can induce K562 cells to erythroid differentiation and improve the expression of globin genes. Mol Cell Biochem. 2013, 382(1-2):127-36
  9. Y.N. Ma, X. Zhang, H.C. Yu, J.W. Zhang. CTD small phosphatase like 2 (CTDSPL2) can increase ε- and γ-globin gene expression in K562 cells and CD34+ cells derived from umbilical cord blood. BMC Cell Biology. 2010. 11:75
  10. Y.N. Ma?, X. Zhang?, J.W. Zhang, Xin-Hua Zhang, Rong-Xin Wang. Screening for trans-acting factors involved in the activating or silencing of g-globin gene during human ontogeny. Biochem. Cell Biol. 2007. 85: 347-357
  11. X. Zhang?, Y.N. Ma?, J.W. Zhang. Human erythroid progenitors from adult bone marrow and cord blood in optimized liquid culture systems respectively maintained adult and neonatal characteristics of globin gene expression. 2007. Biol. Res. 40: 41-35




   王 小 爽

    博士,助理研究员

    电话:010-65105098

    
E-mail: cattle1131@163.com


个人简介

女,1985年10月出生,博士,助理研究员。2011年7月毕业于中国医学科学院基础医学研究所生化与分子生物学系,理学博士。2011-2016年于中国科学院微生物研究所任助理研究员。2016年9月加入中国医学科学院基础医学研究所生化与分子生物学系,医学分子生物学国家重点实验室工作。作为负责人承担国家自然科学基金委青年基金项目。作为第一作者或共作者在Blood、Nature Communications、Proc Natl Acad Sci U S A、J Infect Dis等国际学术期刊上发表SCI论文10篇。目前研究方向为非编码RNA及RNA结合蛋白在髓系分化及白血病调控中的功能机制,以及非编码RNA加工与成熟的分子机制及其在干细胞分化与相关疾病中的功能机理

代表性论文 (? first author; * corresponding author):

  1. Hongmei Zhao?, Xiaoshuang Wang?, Ping Yi?, Yanmin Si, Puwen Tan, Jinrong He , Shan Yu, Yue Ren, Yanni Ma, Junwu Zhang, Dong Wang*, Fang Wang*, Jia Yu*. KSRP specifies monocytic and granulocytic differentiation through regulating miR-129 biogenesis and RUNX1 expression. Nature Communications. 2017. 8 1428
  2. Xiaoshuang Wang?, Xin Fan, Shuai Bi, Ning Li, Beinan Wang*. Toll-like Receptors 2 and 4-Mediated Reciprocal Th17 and Antibody Responses to Group A Streptococcus Infection. J Infect Dis. 15;215(4):644-652. 2017
  3. Zhengyi Zhang?, Jingnan Pi?, Dongling Zou?, Xiaoshuang Wang?, Jiayue Xu?, Shan Yu, Ting Zhang, Feng Li, Hualu Zhao, Fang Wang, Dong Wang*, Yanni Ma*, Jia Yu*. microRNA arm-imbalance partially from targets-mediated decay promotes gastric cancer progression. Nature Communications. In Press.
  4. Ning Li?, Aihui Ren, Xiaoshuang Wang, Xin Fan, Yong Zhao, George. F. Gao, P. Patrick Cleary*, Beinan Wang*. Influenza viral neuraminidase primes bacterial coinfection through TGF-β-mediated expression of host cell receptors. Proc Natl Acad Sci U S A. 112(1):238-43. 2015
  5. Xin Fan?, Xiaoshuang Wang?, Ning Li, Honglian Cui, Baidong Hou, Bin Gao, P. Patrick Cleary*, Beinan Wang*. Sortase A Induces Th17-mediated and Antibody-independent Immunity to Heterologous Serotypes of Group A Streptococci. Plos One.9(9):e107638. 2014
  6. Xiaoshuang Wang?, Jianan Gong?, Jia Yu, Fang Wang, Xinhua Zhang, Xiaolin Yin, Zhenqing Tan, Zimian Luo, Guihua Yang, Chao Shen, Junwu Zhang*. MicroRNA-29a and microRNA-142-3p are regulators of myeloid differentiation and acute myeloid leukemia. Blood. 119(21):4992-5004.2012
  7. Fang Wang?, Xiaoshuang Wang?, Guihua Yang?, Pengfei Zhai, Zhen Xiao, Liangyu Xia, Lirong Chen, Yu Wang, Da Gao, Bintao Huang, Jing Wang, Xiaozhong Wang, Laixi Bi, Nian Liu, Yang Yu, Da Gao, Bintao Huang, Jing Wang, Daobin Zhou, Jianan Gong, Hualu Zhao, Xiuhua Bi, Jia Yu, Junwu Zhang. Down-regulation of miR-29a and miR-142-3p and their diagnostic implication in human acute myeloid leukemia. Mol Bio Rep.39(3):2713-2722.2012
  8. Xiaoshuang Wang?, Junwu Zhang. The microRNAs involved in human myeloid differentiation and myelogenous/myeloblastic leukemia.(Review). J Cell Mol Med.12(5A):1445-55. 2008




  高 玉 风

博士,助理研究员

E-mail: gaoyufeng@ibms.apfhnbc.com

 

个人简介

高玉风,女,1989年11月生,助理研究员。2018年6月毕业于中国科学院北京基因组研究所,基因组学专业,理学博士。2018年7月加入中国医学科学院基础医学研究所生化与分子生物学系,医学分子生物学国家重点实验室工作。作为第一作者在国际学术期刊Blood上发表SCI论文1篇。

目前研究方向为利用组学数据和生物信息学手段描述和刻画造血干细胞发育过程中的动态变化特征。

代表性论文 (? first author; * corresponding author):

Yingchi Zhang?, Yufeng Gao?, Hui Zhang?, Jingliao Zhang, Fuhong He,  Aleˇs Hn??zda, Maoxiang Qian, Xiaoming Liu, Yoshihiro Gocho, Ching-Hon     Pui,  Tao Cheng, Qianfei Wang, Jun J. Yang*, Xiaofan Zhu*, Xin   Liu*.     PDGFRB mutation and tyrosine kinase inhibitor resistance in Ph-like acute lymphoblastic leukemia. Blood. 2018.5.17, 131(20): 2256-2261

 




   王 芳

    博士,教授士生导师

    电话:010-65105098

    E-mail: wo_wfang@hotmail.com

 

个人简介

王芳,女,19832月出生,教授士生导师。2009年7月毕业于中国医学科学院基础医学研究所生化与分子生物学系,理学博士。2009年7月加入中国医学科学院基础医学研究所生化与分子生物学系,医学分子生物学国家重点实验室工作。作为负责人承担国家自然科学基金委青年基金项目、面上项目,作为科研骨干参与科技部973项目,国家重点研发计划。获 “协和新星 ”(2016)、“青年医学人才奖励项目”(2018)等人才计划支持。作为第一作者或通讯作者(含共同)在Cell ResNature CommunicationNucleic Acids Res、Oncogene、J Biol Chem等国际学术期刊上发表SCI论文16篇。目前研究方向为转录后调控与造血谱系分化

代表性论著 (? first author; * corresponding author):

  1. Huang Y?, Tan P?, Wang X, Yi Y, Hu Y, Wang D*, Wang F*. Transcriptomic insights into temporal expression pattern of autophage genes during monocytic and granulocytic differentiation. Autophagy. 2018. 14(3):558-559
  2. Wang F?, Song W?, Zhao H?, Ma Y, Li Y, Zhai D, Pi J, Si Y, Xu J, Dong L, Su R, Zhang M, Zhu Y, Ren X, Miao F, Liu W, Li F, Zhang J, He A, Shan G, Hui J, Wang L, Yu J. Cell Res. 2017.27(3):416-439.
  3. Zhao H, Wang X, Yi P, Si Y, Tan P, He J, Yu S, Ren Y, Ma Y, Zhang J, Wang D, Wang F*, Yu J*. KSRP specifies monocytic and granulocytic differentiation through regulating miR-129 biogenesis and RUNX1 expression. Nat Commun. 2017. 8(1):1428.
  4. Rui Su?, Lei Dong?, Donglin Zou, Hongmei Zhao, Yue Ren, Feng Li, Ping Yi, Lanfang Li, Yong Zhu, Yanni Ma, Jing Wang, Fang Wang*, Jia Yu*. microRNA-23a, -27a and -24 synergistically regulate JAK1/Stat3 cascade and serve as novel therapeutic targets in human acute erythroid leukemia. Oncogene. 2016. 35 (46): 6001- 6014.
  5. Peng W, , Zhang Q, Li C, Zhao F, Wang F*, Yu J*, Ma R*. Long non-coding RNA MEG3 functions as a competing endogenous RNA to regulate gastric cancer progression. J Exp Clin Cancer Res. 2015. 34:79.
  6. Wang F?, Zhu Y?, Guo L, Dong L, Liu H, Yin H, Zhang Z, Li Y, Liu C, Ma Y, Song W, He A, Wang Q, Wang L, Zhang J, Li J, Yu J. A regulatory circuit comprising GATA1/2 switch and microRNA-27a/24 promotes erythropoiesis. 42(1):442-457. 2014.
  7. Zhai PF?, Wang F?, Su R, Lin HS, Jiang CL, Yang GH, Yu J, Zhang JW. The regulatory roles of microRNA-146b-5p and its target platelet-derived growth factor receptor α (PDGFRA) in erythropoiesis and megakaryocytopoiesis. J Biol Chem. 2014 Aug 15;289(33):22600-13.
  8. Yuxia Li, Hua Bai, Zhongzu Zhang, Weihua Li, Lei Dong, Xueju Wei, Yanni Ma, Junwu Zhang, Jia Yu, Guotao Sun*, Fang Wang*. The up-regulation of miR-199b-5p in erythroid differentiation is associated with GATA-1 and NF-E2. Mol. Cells. 37(3): 1-7. 2014.
  9. Y zhu?, D Wang?, F Wang?, T Li1, L Dong, H Liu, Y Ma, F Jiang, H Yin, W Yan, H Dong, M Luo, Z Tang, G Zhang, Q Wang, J Zhang, J Zhou, J Yu. A comprehensive analysis of GATA-1-regulated miRNAs reveals miR-23a to be a positive modulator of erythropiesis. Nucleic Acids Res. 41(7):4129- 43. 2013.
  10. F Wang?, X Wang?, G Yang?, P Zhai, Z Xiao, L Xia, L Chen, Y Wang, X Wang, L Bi, N Liu, Y Yu, D Gao, B Huang, J Wang, D Zhou, J Gong, H Zhao, X Bi, J Yu, J Zhang. miR-29a and miR-142-3p downregulation and diagnostic implication in human acute myeloid leukemia. Mol Biol Rep. 39 (3):2713-22. 2012.
  11. F Wang, J Yu, G Yang, X Wang, J Zhang. Regulation of erythroid differention by miR-376a and its targets. Cell Res. 21 (8): 1196-1209. 2011.