余佳:中国医学科学院基础医学研究所生化系研究员-中文百科频道

人物经历

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。

主要成就

科研成就

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CellStemCell、EMBOJournal、NatureCommunications、CellResearch、CancerResearch、NucleicAcidsResearch、Autophagy、Oncogene、MCB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NatureMedicine、Blood及Elife等学术期刊发表多篇论文。

研究成果简介：

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.通过系统性调查假基因的表达特征及与疾病的关联，发现假基因HBBP1演化出调控人红细胞发育及疾病的重要作用及全新机制（Developmental Cell,2021）;

2.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）；同时描绘了精子发育全程的lncRNA图谱，揭示了其中关键的功能性lncRNA（Genome Res.,2020）;

3.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）;

4.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）；

5.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）；

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);

7.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(EMBO J.,2015)；系统性揭示了RNA结合蛋白在胚胎干细胞多能性退出中的作用，发现hnRNPLL通过调控mRNA可变剪接促进胚胎干细胞退出多能性（EMBO J., 2020）;

8.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, 2012；Cell Death&Differentiation,2014)；

9.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)；

10.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, 016)；通过全外显子组和转录组测序描绘了无功能垂体内分泌肿瘤各亚型临床表型异质性的分子图谱，提出了侵袭性诊断的新型分子标志物 (Theranostics,2021);

11.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(Nat. Commun., 2019； Mol Oncol. 2019；Cancer Research, 2015; Carcinogenesis, 2014; Cancer Research,2010; J Hepatol, 2010;)；

12.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(Cancer Research, 2020; Nucl. Acids Res, 2020; Mol. Cel. Biol,2015)。

在研项目：

1.科技部国家重点研发计划发育与代谢专项，2019-2024、造血稳态的代谢调控机理、首席科学家。

2.国家杰出青年科学基金，2018-2022、造血细胞发育调控、主持。

3.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。

4.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。

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):

Yanni Ma†*, Siqi Liu†, Jie Gao†, Chunyan Chen†, Xin Zhang†, Hao Yuan, Zhongyang Chen, Xiaolin Yin, Chenguang Sun, Yanan Mao, Fanqi Zhou, Yi Shao, Qian Liu, Jiayue Xu, Li Cheng, Daqi Yu, Pingping Li, Ping Yi, Jiahuan He, Guangfeng Geng, Qing Guo, Yanmin Si, Hualu Zhao, Haipeng Li, Graham L Banes, He Liu, Yukio Nakamura, Ryo Kurita, Yue Huang, Xiaoshuang Wang, Fang Wang, Gang Fang, James Douglas Engel, Lihong Shi*, Yong E Zhang*, Jia Yu*. Genome-wide analysis of pseudogenes reveals HBBP1's human-specific essentiality in erythropoiesis and implication in β-thalassemia. Developmental Cell. 2021 Jan 12:S1534-5807(20)31025-X.

Xue Wang†, Changyun Ping†, Puwen Tan†, Chenguang Sun, Guang Liu, Tao Liu, Shuchun Yang, Yanmin Si, Lijun Zhao, Yongfei Hu, Yuyan Jia, Xiaoshuang Wang, Meili Zhang, Fang Wang, Dong Wang*, Jia Yu*, Yanni Ma*, Yue Huang*. hnRNPLL controls pluripotency exit of embryonic stem cells by modulating alternative splicing of Tbx3 and Bptf. EMBO J. 2020 Dec 22:e104729.

Kai Li†, Jiayue Xu†, Yanyun Luo†, Dingfeng Zou, Ruiqin Han, Shunshun Zhong, Qing Zhao, Xinyu Mang , Mengzhen Li, Yanmin Si , Yan Lu, Pengyu Li, Cheng Jin, Zhipeng Wang, Fang Wang, Shiying Miao, Bo Wen, Linfang Wang, Yanni Ma*, Jia Yu*, Wei Song*. Panoramic transcriptome analysis and functional screening of long noncoding RNAs in mouse spermatogenesis. Genome Res. 2021 Jan;31(1):13-26.

Jingnan Pi†, Wen Wang†, Ming Ji, Xiaoshuang Wang, Xueju Wei, Jing Jin, Tao Liu, Jiaqi Qiang, Zhihong Qi, Feng Li, Yue Liu, Yanni Ma, Yanmin Si, Yue Huo, Yufeng Gao, Yiying Chen, Lei Dong, Rui Su, Jianjun Chen, Shuan Rao, Ping Yi, Shuyang Yu, Fang Wang*, Jia Yu*. YTHDF1 promotes gastric carcinogenesis through controlling the translation of FZD7. Cancer Research. 2020 Aug 11; canres.00662020.

Xinjie Bao†, Gengchao Wang†, Shan Yu†, Jian Sun, Hualu Zhao, Yanni Ma, Fang Wang, Xiaoshuang Wang*, Renzhi Wang*, Jia Yu*. Transcriptomic analysis reveals a tumor subtype-mRNA classifier for invasive non-functioning pituitary adenoma diagnostics. Theranostics. 2021 Jan 1; 11(1):132-146.

Tao Liu†, Qinglv Wei†, Jing Jin†, Qingya Luo, Yi Liu, Yu Yang, Chunming Cheng, Lanfang Li, Jingnan Pi, Yanmin Si, Hualiang Xiao, Li Li, Shuan Rao, Fang Wang, Jianhua Yu, Jia Yu*, Dongling Zou*, Ping Yi*. The m6A reader YTHDF1 promotes ovarian cancer progression via augmenting EIF3C translation. Nucleic Acids Research. 2020. 48(7):3816-3831.

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. 2019 Sep. 10 (1):4397.

Puwen Tan†, Yue Ren†, Yuncong Zhang†, Yunqing Lin, Tianyu Cui, Yan Huang, Yang Zhang, Lin Ning, Jia Yu, Shuai Gao, Dong Wang & He Huang*. Dissecting dynamic expression of autophagy-related genes during human fetal digestive tract development via single- cell RNA sequencing, Autophagy, 2019 Nov. 15:11, 2019-2021.

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

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

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, 1536–1544

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)

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

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

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

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

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

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

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):361–378

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

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

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)

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

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)

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

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

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

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)

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)

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)

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)

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)

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)

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)

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:

MicroRNA研究方法与应用.中国协和医科大学出版社.2008.(副主编)

MicroRNA鉴定与功能分析技术.化学工业出版社.2012.(主编)