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，也是生命科学领域的新兴学科。过去二十年里，这一学科得到长足发展，特别是高通量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。近期关于RNA修饰的研究已经衍生出RNA表观遗传学这一学科方向，也诞生了表观转录组（Epitranscriptome）概念；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，更是大大扩充了人类对于自身，乃至各个物种基本遗传和进化的认知。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，有什么独特的分子调控机制，在转化医学中是否有应用价值？ 课题组主攻下列科学问题： 1、造血干细胞起源、异质性、谱系分化与生态的分子动力学图谱； 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作用机理； 3、胚胎及成体干细胞功能的RNA调控机理； 4、RNA代谢及调控的生理功能和转化医学应用。

一、细胞与生态图谱

1. 利用深度RNA-sequencing结合全基因组DNA-sequencing绘制出造血谱系RNA编辑图谱，发现调控造血干细胞分化的关键编辑基因及其入核后的转录调控机理（Blood, 2021）；[被选为封面文章，USCD教授Catriona Jamieson 在Blood同期进行述评：Commentary: Upping the Antizyme: AZIN1 Directs Stem Cell Fate]

2. 利用深度RNA-sequencing绘制出精子发育全程的lncRNA图谱，鉴定功能性lncRNA及其转录调控机理（Genome Research, 2020）;

3. 利用深度RNA-sequencing绘制出人垂体瘤转录组图谱，结合外泌体分离与机器学习获得首个侵袭性垂体瘤血液诊断panel并申请中国专利（Theranostics, 2020）;

4. 利用单细胞测序技术绘制出造血干细胞发育全程的lncRNA及RNA剪接图谱，揭示调控“内皮-造血”转换的关键lncRNA及RNA可变剪接事件（Cell Stem Cell, 2019； Science Advances 2022），[其中Cell Stem Cell文章被Faculty 1000推荐为必读文章]；

5. 利用RNA-sequencing绘制出造血干细胞向粒系/单核系分化命运选择中的自噬分子图谱（Autophagy, 2018）；

6. 利用单细胞测序技术绘制出造血干细胞发育全程自噬分子图谱（Autophagy, 2017）。

二、非编码RNA生成、加工、成熟及功能

1. 通过系统性调查假基因的表达特征及与疾病的关联，发现假基因来源非编码RNA-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）; [ISEH(国际实验血液学会)官方杂志Experimental Hematology特邀余佳和马艳妮教授撰写领域展望：Perspective: Pseudogenes and their potential functions in hematopoiesis]

2. 揭示肿瘤进程中部分microRNA存在双臂表达的“arm imbalance”现象，发现“靶基因RNA引导的microRNA降解”可部分解释其发生机制，提出靶向“microRNA双臂”的肿瘤治疗新策略（Nature Communications, 2019）;

3. 解决了自microRNA发现以来的一个重要科学问题即microRNA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RNA顺式作用元件，并且这些RNA顺式作用元件可通过蛋白-RNA互作及其所介导RNA高级结构参与microRNA加工（Cell Research, 2017）；

4. 揭示一个或多个RNA顺式作用元件通过蛋白-RNA互作及其所介导的RNA高级结构参与microRNA加工，并调控造血干细胞分化 （Nature Communications, 2017）；

5. 建立蛋白质-RNA互作事件数据库Raid 2.0 （Nucleic Acids Research, 2017）。

三、 干细胞命运调控

1. 系统性揭示染色质结合型RNA结合蛋白（Che-RBP）在造血干细胞分化中的蛋白质/DNA及蛋白质/RNA结合规律，发现Che-RBP QKI-5通过调控DNA转录促进单核细胞分化（Genome Biology. 2021）;

2. 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（The EMBO J. 2021）;

3. 鉴定胚胎干细胞定向中胚层分化的关键microRNA基因簇并发现其“表型冗余”现象和产生机理 (The EMBO J. 2015)。

四、RNA代谢的生理功能和转化医学应用

1. 发现RNA结合蛋白介导的RNA修饰参与肿瘤发生，是肿瘤治疗的新靶标（Cancer Research, 2021; Nucleic Acids Research, 2020）；

2. 鉴定了多个实体肿瘤发生发展相关的microRNA并阐明其致癌机理及转化潜力  (Cancer Research, 2010, 2015; Carcinogenesis, 2014; Journal of Hepatology, 2010)；

3. 鉴定了成体造血干细胞向髓系分化的关键microRNA基因/基因簇 (Blood, 2012；Cell Death&Differentiation, 2014)；

4. 揭示microRNA与红系分化关键转录因子间的多重互作机制 (Nucleic Acids Research, 2013, 2014; Mol. Cel. Biol, 2013)；发现RISC复合物成员Ago2介导的microRNA间"cross talk"是红系分化的重要分子事件(Cell Research, 2011)；

5. 鉴定了多个可用于急性髓系白血病诊治的microRNA靶标(Oncogene, 2015, 2016; PLoS Genetics, 2016)。

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。

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

1.Qing You†, Fang Wang†, Rong Du, Jingnan Pi, Huayi Wang, Yue Huo, Jingyi Liu, Chen Wang, Jia Yu*, Yanlian Yang*, Ling Zhu*. m6A Reader YTHDF1-Targeting Engineered Small Extracellular Vesicles for Gastric Cancer Therapy via Epigenetic and Immune Regulation. Adv Mater. 2022 Dec 9:e2204910.

2.Hongwei Chen† , Xin Wen† , Shanshan Liu† , Tian Sun , Hua Song , Fang Wang , Jiayue Xu, Yueyang Zhang, Yuanjin Zhao, Jia Yu* , Lingyun Sun*. Dissecting Heterogeneity Reveals a Unique BAMBIhigh MFGE8high Subpopulation of Human UC-MSCs. Adv Sci (Weinh). 2022 Nov 14. 10(1):e2202510.

3.Xueju Wei†, Yue Huo†, Jingnan Pi†, Yufeng Gao†, Shuan Rao†, Manman He†, Qinglv Wei, Peng Song, Yiying Chen, Dongxu Lu, Wei Song, Junbo Liang, lingjie Xu, Haixia Wang, Guolin Hong, Yuehong Guo, Yanmin Si, Jiayue Xu, Xiaoshuang Wang, Yanni Ma, Shuyang Yu, Dongling Zou*, Jing Jin*, Fang Wang*, Jia Yu*. METTL3 preferentially enhances non-m6A translation of epigenetic factors and promotes tumourigenesis. Nature Cell Biology. 2022 Aug. 24(8):1278-1290.

4.Fang Wang†, Puwen Tan†, Pengcheng Zhang†, Yue Ren†, Jie Zhou, Yunqiao Li, Siyuan Hou, Shuaili Li, Linlin Zhang, Yanni Ma, Chaojie Wang, Wanbo Tang, Xiaoshuang Wang, Yue Huo, Yongfei Hu, Tianyu Cui, Chao Niu, Dong Wang*, Bing Liu*, Yu Lan*, Jia Yu*. Single-cell architecture and functional requirement of alternative splicing during hematopoietic stem cell formation. Sci Adv. 2022 Jan 7;8(1):eabg5369.

5.Yanni Ma†*, Zhongyang Chen, Jia Yu*. Pseudogenes and their potential functions in hematopoiesis. Experimental Hematology. 2021 Nov. 103:24-29.

6.Fengjiao Wang†, Jiahuan He†, Siqi Liu†, Ai Gao, Liu Yang, Guohuan Sun, Wanqiu Ding, Chuanyun Li, Fanglin Gou, Manman He, Fang Wang, Xiaoshuang Wang, Xiangnan Zhao, Ping Zhu, Shao Hao, Yanni Ma*, Hui Cheng*, Jia Yu*, Tao Cheng*. A comprehensive RNA editome reveals that edited Azin1 partners with DDX1 to enable hematopoietic stem cell differentiation. Blood. 2021 Nov 18. 138(20):1939-1952.

7.Yue Ren†, Yue Huo†, Weiqian Li†, Manman He, Siqi Liu, Jiabing Yang, Hongmei Zhao, Lingjie Xu, Yuehong Guo, Yanmin Si, Hualu Zhao, Shuan Rao, Jing Wang, Yanni Ma, Xiaoshuang Wang*, Jia Yu*, Fang Wang*. A global screening identifies chromatin-enriched RNA-binding proteins and the transcriptional regulatory activity of QKI5 during monocytic differentiation. Genome Biology. 2021 Oct 14 22(1).290.

8.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. 2021 May 15. 81(10): 2651-2665.

9.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 Feb 22. 56(4):478-493.e11.

10.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. The EMBO Journal. 2021 Feb 15. 40(4):e104729.

11.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 Research. 2021 Jan. 31(1):13-26.

12.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.

13.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 Apr 17. 48(7):3816-3831.

14.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 27. 10(1):4397.

15.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*, 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(2): 285-298.e5.

16.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 Oct. 24(10):1536–1544.

17.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)

18.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 Nov 10. 8(1):1428.

19.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.

20.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.

21.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.

22.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.

23.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 Feb 3. 34(3):361–378.

24.Jianan Gong†, Jianxiong Li, Yi Wang, Changzhegn 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 microRNA-29 family expression and investigation of their mechanistic roles in gastric cancer. Carcinogenesis. 2014 Feb. 35(2):497-506.

25.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.

26.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.

27.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.

28.Jia Yu*, Fang Wang. Recent progress in microRNA study: Benefits from technique advance. SCIENCE CHINA Life Sciences. 2012 July. 55(7):649-50. (Invited comment)

29.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.

30.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.

31.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.

32.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.

33.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. (Cover story)

34.Robert M. Lavker†*, Jia Yu and David G Ryan. The Tiny World of MicroRNAsin the Cross Hairs of the Mammalian Eye. Human Genomics. 2009 Jul. 3(4):332-348. (Review)

35.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.

余佳，男，1978年生，研究员，博士生导师，北京协和医学院长聘教授（首批）、RNA与干细胞生物学课题组组长，中国医学科学院RNA与造血调控研究重点实验室主任，医学分子生物学国家重点实验室PI。获得国家杰出青年科学基金(2017，生命科学部)，长江学者奖励计划(2017)，百千万人才工程国家级人选（2019），国务院政府特殊津贴（2020）等人才项目支持。担任科技部十三五“发育编程及其代谢调节”重点研发专项首席科学家，十四五“发育编程及其代谢调节”重点研发专项总体专家组、指南编写组成员。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国家重点研发计划、973子课题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、干细胞命运及转化医学，综合运用多种组学及计算生物学方法，干细胞培养及基因操纵等体外实验技术，干细胞移植、基因敲除小鼠及谱系示踪等体内技术，结合生化与分子生物学手段，研究RNA、互作蛋白质及相关遗传信息传递过程在干细胞或疾病中的功能和调控机理。在组织器官发育与疾病的细胞图谱、非编码RNA生成与加工新机理、干细胞命运调控新机制等方面取得突出成果，相关研究成果作为通讯作者（含共同）在Cell Stem Cell、Developmental Cell、Blood、Cell Research、Science Advances、EMBO Journal（2015，2021）、Genome Research、Nature Communications（2017，2019）、Genome Biology 、Cancer Research（2010，2015，2020）、Nucleic Acids Research（2013，2014，2017，2020）、Autophagy、Oncogene、MCB等国际主流学术期刊上发表SCI论文30余篇，被引用4000余次。获教育部自然科学二等奖（2018）。现担任中国生理学会血液生理专业委员会理事，中国细胞生物学会干细胞专业委员会理事， 北京市生化协会理事。担任Blood, Nature Communications, Nucleic Acids Research, Oncogene, Cancer Research, MCB, JBC等杂志特邀审稿人。