餘佳:中國醫學科學院基礎醫學研究所生化系研究員-中文百科頻道

人物經曆

2006年7月畢業于中國醫學科學院/北京協和醫學院基礎醫學研究所生化與分子生物學系，理學博士。

2006-2007年在美國伊利諾伊大學芝加哥分校工作(Post-doc)。

2007-2009年在美國西北大學Feinberg醫學院工作(Post-doc)。2009年10月回國加入中國醫學科學院基礎醫學研究所生化系及醫學分子生物學國家重點實驗室。

主要成就

科研成就

作為負責人承擔國家自然科學基金委重大研究計劃、重點項目及面上項目等；作為負責人承擔科技部973子課題、國家重點研發計劃及國家重大研究計劃。餘佳博士同時擔任中國醫學科學院-以色列Weizmann研究所聯合實驗室PI，中國醫學科學院“醫學與健康科技創新工程”創新團隊項目首席科學家，人血細胞分子圖譜（ABC）研究聯盟首批倡議及參加成員。

餘佳實驗室主要興趣集中在造血調控、譜系分化及再生，綜合運用幹細胞培養及基因操縱等體外實驗，造血幹細胞移植、基因敲除小鼠及譜系示蹤等體内技術，結合多種單細胞組學及計算生物學手段，研究RNA及其互作蛋白質在幹細胞中的功能和調控機理。

近五年作為通訊作者在CellStemCell、EMBOJournal、NatureCommunications、CellResearch、CancerResearch、NucleicAcidsResearch、Autophagy、Oncogene、MCB等國際學術期刊上發表SCI論文20餘篇，被引用1900餘次，也作為主要作者在NatureMedicine、Blood及Elife等學術期刊發表多篇論文。

研究成果簡介：

實驗室過去五年主要以成體造血幹細胞譜系分化、胚胎幹細胞向中胚層定向分化及消化道癌症為研究模型或對象，鑒定其中起重要作用的非編碼RNA及其互作蛋白質并研究它們的作用機理，取得了一系列重要成果：

1.通過系統性調查假基因的表達特征及與疾病的關聯，發現假基因HBBP1演化出調控人紅細胞發育及疾病的重要作用及全新機制（Developmental Cell,2021）;

2.利用單細胞測序技術繪制出造血幹細胞發育全程的lncRNA圖譜，并揭示調控“内皮-造血”轉換的關鍵lncRNA及其表觀遺傳調控機理（Cell Stem Cell,2019）；同時描繪了精子發育全程的lncRNA圖譜，揭示了其中關鍵的功能性lncRNA（Genome Res.,2020）;

3.利用轉錄組測序技術揭示造血幹細胞向粒系/單核系分化命運選擇中的自噬分子表型（Autophagy,2018）;

4.揭示RNA結合蛋白QKI5調控造血幹細胞向紅細胞分化（Cell Research, 2017），RNA結合蛋白KSRP調控造血幹細胞向粒系/單核系分化命運選擇（Nat. Commun., 2017）；

5.利用單細胞測序技術繪制出造血幹細胞發育過程mRNA分子表達譜并證明自噬相關分子在造血幹細胞發育中存在階段特異性表達及重要功能（Autophagy,2017）；

解決了自微小RNA發現以來的一個重要科學問題即微小RNA初級轉錄本莖環結構遠端序列是否具有調節功能？證明莖環遠端序列存在功能性RNA模體，并且這些RNA模體可通過RNA結合蛋白和RNA高級結構介導參與微小RNA加工（Cell Research, 2017）；基于該理論進一步通過生物信息學手段建立了蛋白質-RNA互作事件數據庫Raid 2.0 (Nucl. Acids Res,2017);

7.鑒定了胚胎幹細胞定向中胚層分化的關鍵微小RNA基因簇并發現其“表型彈性”現象和産生機理(EMBO J.,2015)；系統性揭示了RNA結合蛋白在胚胎幹細胞多能性退出中的作用，發現hnRNPLL通過調控mRNA可變剪接促進胚胎幹細胞退出多能性（EMBO J., 2020）;

8.鑒定了成體造血幹細胞向髓系分化的關鍵微小RNA基因/基因簇(Blood, 2012；Cell Death&Differentiation,2014)；

9.揭示微小RNA與紅系分化關鍵轉錄因子間的多重互作機制(Nucl. Acids Res, 2013, 2014; Mol. Cel. Biol, 2013)；發現RISC複合物成員Ago2介導的微小間"cross talk"是紅系分化的重要分子事件(Cell Research,2011)；

10.鑒定了多個可用于急性髓系白血病診治的微小RNA靶标(Oncogene,2015,2016; PLoS Genetics, 016)；通過全外顯子組和轉錄組測序描繪了無功能垂體内分泌腫瘤各亞型臨床表型異質性的分子圖譜，提出了侵襲性診斷的新型分子标志物 (Theranostics,2021);

11.鑒定了多個消化道癌症發生相關的微小RNA并闡明其緻癌機理(Nat. Commun., 2019； Mol Oncol. 2019；Cancer Research, 2015; Carcinogenesis, 2014; Cancer Research,2010; J Hepatol, 2010;)；

12.發現RNA結合蛋白及長非編碼RNA可以調控髓系分化及胃癌發生(Cancer Research, 2020; Nucl. Acids Res, 2020; Mol. Cel. Biol,2015)。

在研項目：

1.科技部國家重點研發計劃發育與代謝專項，2019-2024、造血穩态的代謝調控機理、首席科學家。

2.國家傑出青年科學基金，2018-2022、造血細胞發育調控、主持。

3.科技部國家重點研發計劃幹細胞及轉化專項，2016-2020、造血幹細胞的發育規律及調控機制、參與。

4.國家自然科學基金重點項目，2016-2020、長鍊非編碼RNA在造血髓系鍊系呈遞及分化發育中的功能及機制研究、主持。

5.中國醫學科學院“醫學與健康科技創新工程”創新團隊項目，2017-2020、造血幹細胞異質性的表觀遺傳調控機理、首席科學家。

6.中國醫學科學院“醫學與健康科技創新工程”重大協同創新項目，2017-2020、人類血細胞圖譜計劃、參與（負責人類紅細胞圖譜）。

代表性論著 († 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研究方法與應用.中國協和醫科大學出版社.2008.(副主編)

MicroRNA鑒定與功能分析技術.化學工業出版社.2012.(主編)