教育背景

2003 美国密歇根大学医学院生物化学系 （导师：Randal J. Kaufman） 博士

1996 南开大学生命科学院 学士

工作经历

2004-2010 博士后、讲师，哈佛大学医学院、Dana-Farber 癌症研究所和波士顿儿童医院（导师：Stuart Orkin）

2010-2016 清华大学医学院特别研究员、准聘副教授（tenure-track） 

2011-2016 清华生命科学联合中心研究员 

2016-2020 清华大学医学院长聘副教授 

2016- 清华-北大生命科学联合中心高级研究员

2017-2022 长江学者奖励计划特聘教授

2020-2024 清华大学医学院长聘教授、生命科学联合中心高级研究员

2024-至今 清华大学基础医学院长聘教授、生命科学联合中心高级研究员

研究领域

非编码基因组和细胞命运决定: 研究非编码基因组、转录、染色质折叠、以及细胞核结构和功能的基层规律；深入微观概率的调控方式，探索生命的物理和数学基础；进行细胞核的物理建模，研究遗传信息解读过程的物理特性，认识不同层次的调控和细胞表型的涌现，揭示从DNA到RNA和蛋白以及细胞表型的生命信息流背后的程序化算法，为全面认识基因组功能和细胞命运决定提供新的理论框架。

科学贡献

提出转座子重复序列（L1 和 B1/Alu）是大尺度染色质三维结构形成的遗传分子基础; 揭示非编码ncRNA顺式调控邻近基因的表达是一种普遍模式，并通过RNA结合蛋白和相分离反馈调控转录和染色质状态；揭示细胞核ncRNA系统性地协调染色质折叠、转录和翻译等细胞功能。

现为《eLIFE》《Cell Reports》《EMBO Reports》《Molecular Omics》等期刊编委。

荣誉奖励

2021 谈家桢生命科学创新奖

2020 – 2024 国家杰出青年科学基金项目获得者

2017 – 2022 长江学者奖励计划特聘教授

2016 Royan International Research Award，伊朗

2013 求是杰出青年

2009 美国 Claudia Adams Barr 癌症研究奖

代表性论文

1.Han X, Xing L,…, Deng W, and Shen X. Nuclear RNA homeostasis promotes systems-level coordination

for cell fate and vitality. Cell Stem Cell. 2024. Accepted.

2.Li S, Shen X. Long interspersed nuclear element 1 and B1/Alu repeats blueprint genome compartmentalization. Curr Opin Genet Dev. 2023. doi: 10.1016/j.gde.2023.102049.

3.Shao W, Bi X, Pan Y, Gao B, Wu J, Yin Y, Liu Z, Zhang W, Jiang X, Ren W, Xu Y, Wu Z, Wang K, Zhan G, Lu Y, Han X, Li T, Wang J, Li G, Deng H, Li B*, Shen X*. Phase separation of RNA-binding protein promotes polymerase engagement and transcription. Nature Chemical Biology. 2022 Jan;18(1):70-80. (* co-corresponding).

4.Lu J.Y.^#, Chang L^#, Li T^#, Wang T, Yin Y, Zhan G, Han X, Zhang K, Tao Y, Percharde M, Wang L, Peng Q, Yan P, Zhang H, Bi X, Shao W, Hong Y, Wu Z, Ma R, Wang P, Li W, Zhang J, Chang Z, Hou Y, Zhu B, Ramalho-Santos M, Li P, Xie W, Na J, Sun Y*, Shen X*. Homotypic clustering of L1 and B1/Alu repeats compartmentalizes the 3D genome. Cell Research. 2021 Jun;31(6):613-630. doi: 10.1038/s41422-020-00466-6. (* co-corresponding).

5.Yan P, Lu JY, Niu J, Gao J, Zhang MQ, Yin Y, Shen X. LncRNA Platr22 promotes super-enhancer activity and stem cell pluripotency. J Mol Cell Biol. 2021 Aug 4;13(4):295-313.

6.Yin Y*, Lu JY, Zhang X, Shao W, Xu Y, Li P, Hong Y, Cui L, Shan G, Tian B, Zhang Q, Shen X*. (2020) U1 snRNP regulates chromatin retention of noncoding RNAs. Nature. 580(7801):147-150. (* co-corresponding)

7.Lu JY, Shao W, Chang L, Yin Y, Li T, Zhang H, Hong Y, Percharde M, Guo L, Wu Z, Liu L, Liu W, Yan P, Ramalho-Santos M, Sun Y, Shen X. (2020) Genomic repeats categorize genes with distinct functions for orchestrated regulation. Cell Reports. 30(10):3296-3311. doi: 10.1016/j.celrep.2020.02.048.

8.Zhang H*, Wu Z, Lu JY, Huang B, Zhou H, Xie W, Wang J, Shen X*. (2020) DEAD-box helicase 18 counteracts PRC2 to safeguard ribosomal DNA in pluripotency regulation. Cell Reports. 2020. 30(1):81-97. (* co-corresponding)

9.Bi X., Shen X. (2020) Transcriptome-Wide Mapping of Protein–RNA Interactions. In: ➢rom U. (eds) RNA-Chromatin Interactions. Methods in Molecular Biology, vol 2161. Humana, New York, NY.

10.Yin Y., Shen X. (2020) Identification of cis-Elements for RNA Subcellular Localization Through REL-seq. In: ➢rom U. (eds) RNA-Chromatin Interactions. Methods in Molecular Biology, vol 2161. Humana, New York, NY.

11.Bi X*, Zhang X, Shen X*. (2020) Transcriptome-Wide Profiling of Protein-RNA Interactions by Cross-Linking and Immunoprecipitation Mediated by FLAG-Biotin Tandem Purification. J. Vis. Exp. (159), e60730, doi:10.3791/60730 (2020). (* co-corresponding)

12.Zhao J., Wang M., Chang L., Yu J., Song A., Liu C., Huang W., Zhang T., Wu X., Shen X., Zhu B., Li G. (2020) RYBP/YAF2-PRC1 Complexes and Histone H1-dependent Chromatin Compaction Mediate Propagation of H2AK119ub1 During Cell Division. Nat Cell Biol. 2020 Apr;22(4):439-452.

13.Liu L, Lu J.Y, Xing X, Li T, Li F, Yang X, Shen X. (2019) IDH1 fine-tunes cap-dependent translation initiation. J Mol Cell Biol. 11(10):816-828.

14.Han X, Zhang J, Liu Y, Fan X, Ai S, Luo Y, Li X, Jin H, Luo S, Zheng H, Yue Y, Chang Z, Yang Z, Tang F, He A*, Shen X*. (2019) The lncRNA Hand2os1/Uph locus orchestrates heart development through regulation of precise expression HAND2. Development. 2019. 146, dev176198. (* co-corresponding)

15.Bi X, Xu Y, Li T, Li X, Li W, Shao W, Wang K, Zhan G, Wu Z, Liu W, Yin Y, Lu J.Y., Wang L, Zhao J, Wu J, Na J, Li G, Li P, Shen X. (2019) RNA targets ribosome biogenesis factor WDR43 to chromatin for transcription and pluripotency control. Mol Cell. 75: 102-116.

· Recommended by F1000 Faculty Member

16.Liu L, Li T, Song G, He Q, Yin Y, Lu J.Y., Bi X, Wang K, Luo S, Chen YS, Yang Y, Sun BF, Yang YG, Wu J, Zhu H*, Shen X*. (2019) Insight into novel RNA-binding activities via large-scale analysis of lncRNA-bound proteome and IDH1-bound transcriptome. Nucleic Acids Res. 47(5): 2244-2262. (*co-corresponding)

17.Percharde M, Lin CJ, Yin Y, Guan J, Peixoto GA, Bulut-Karslioglu A, Biechele S, Huang B, Shen X, Ramalho-Santos M. (2018) A LINE1-Nucleolin Partnership Regulates Early Development and ESC Identity. Cell. 174(2):391-405.

18.Han X, Luo S, Peng G, Lu JY, Cui G, Liu L, Yan P, Yin Y, Liu W, Wang R, Chang Z, Na J, Jing N*, Shen X*. (2018) Mouse knockout models reveal largely dispensable but context-dependent functions of lncRNAs during development. J Mol Cell Biol. 10(2):175-178. (* co-corresponding)

19.Guallar D, Bi X, Pardavila JA, Huang X, Saenz C, Shi X, Zhou H, Faiola F, Ding J, Haruehanroengra P, Yang F, Li D, Sanchez-Priego C, Saunders A, Pan F, Valdes VJ, Kelley K, Blanco MG, Chen L, Wang H, Sheng J, Xu M, Fidalgo M, Shen X, Wang J. (2018) RNA-dependent chromatin targeting of TET2 for endogenous retrovirus control in pluripotent stem cells. Nat Genet. 50(3):443-451.

20.Yan P, Luo S, Lu JY, Shen X. (2017) Cis- and trans-acting lncRNAs in pluripotency and reprogramming. Current Opinion in Genetics & Development. 46:170-178.

21.Luo S, Lu J, Liu L, Yin Y, Han X, Xu R, Wu B, Liu W, Yan P, Shao W, Chen C, Lu Z, Na J, Tang F, Wang J, Zhang Y.E. and Shen X. (2016) Divergent lncRNAs regulate gene expression and lineage differentiation in pluripotent cells. Cell Stem Cell. 18(5):637-52.

· Previewed by Ounzain S and Pedrazzini T. (2016) Divergent Paths Lnc Cell Fates. Cell Stem Cell. 18(5):561-2

22.Yin Y, Yan P, Lu J, Song G, Zhu Y, Li Z, Zhao Y, Shen B, Huang X, Zhu H, Orkin SH, Shen X. (2015) Opposing roles for the lncRNA Haunt and its genomic locus in regulating HOXA gene activation during embryonic stem cell differentiation. Cell Stem Cell. 16(5):504-16.

· Recommended by F1000 Faculty Member.

· Previewed by Lin N, Dang J and Rana TM. (2015) Haunting the HOXA locus: two faces of lncRNA regulation. Cell Stem Cell. 16(5):449-50

23.Ding J, Huang X, Shao N, Zhou H, Lee D, Faiola F, Fidalgo M, Guallar D, Saunders A, Shliaha P, Wang H, Waghray A, Papatsenko D, Sánchez-Priego C, Li D, Yuan Y, Lesmischka I, Shen L, Kelley K, Deng H, Shen X, Wang J. (2015) Tex10 coordinates epigenetic control of the super-enhancer activity in pluripotency and reprogramming. Cell Stem Cell. 16(6):653-68.

24.Das PP, Hendrix DA, Apostolou E, Buchner AH, Canver MC, Beyaz S, Ljuboja D, Kuintzle R, Kim W, Karnik R, Shao Z, Xie H, Xu J, De Los Angeles A, Zhang Y, Choe J, Jun DL, Shen X, Gregory RI, Daley GQ, Meissner A, Kellis M, Hochedlinger K, Kim J, Orkin SH. (2015) PRC2 Is Required to Maintain Expression of the Maternal Gtl2-Rian-Mirg Locus by Preventing De Novo DNA Methylation in Mouse Embryonic Stem Cells. Cell Rep. 12(9):1456-70.

25.Yuan G, Ma B, Yuan W, Zhang Z, Chen P, Ding X, Feng L, Shen X, Chen S, Li G, Zhu B. (2013) Histone H2A ubiquitination inhibits the enzymatic activity of H3 lysine 36 methyltransferases. J Biol Chem. 288(43):30382-42.

26.Sakaki K, Yoshina S, Shen X, Han J, DeSantis MR, Xiong M, Mitani S, Kaufman RJ. (2012) RNA surveillance is required for endoplasmic reticulum homeostasis. Proc Natl Acad Sci USA. 109(21):8079-84.

27.He A, Shen X, Ma Q, Cao J, Gise AV, Zhou P, Wang G, Marquez VE, Orkin SH, Pu WT. (2012) PRC2 directly methylates GATA4 and represses its transcriptional activity. Genes & Development. 26: 37-42.

28.Lin W, Cao J, Liu J, Beshiri ML, Fujiwara Y, Francis J, Cherniack AD, Geisen C, Blair LP, Zou MR, Shen X, Kawamori D, Liu Z, Grisanzio C, Watanabe H, Minamishima YA, Zhang Q, Kulkarni RN, Signoretti S, Rodig SJ, Bronson RT, Orkin SH, Tuck DP, Benevolenskaya EV, Meyerson M, Kaelin WG Jr, Yan Q. (2011) Loss of the retinoblastoma binding protein 2 (RBP2) histone demethylase suppresses tumorigenesis in mice lacking Rb1 or Men1. Proc Natl Acad Sci USA. 108(33):13379-86.

29.Wilson BG, Wang X, Shen X, McKenna ES, Lemieux ME, Cho Y, Koellhoffer EC, Pomeroy SL, Orkin SH, Roberts CWM. (2010) Epigenetic antagonism between Polycomb and SWI/SNF complexes during oncogenic transformation. Cancer Cell. 18(4):316-28.

30.Shen X, Kim W, Fujiwara Y, Simon MD, Liu Y, Mysliwiec MR, Yuan G, Lee Y, Orkin SH. (2009) Jumonji modulates Polycomb activity and self-renewal versus differentiation of stem cells. Cell. 2009. 139(7): 1303-1314.

· Previewed by Barbara Panning. (2010) Fine-tuning Silencing. Cell Stem Cell. 6(1):3-4.

31.Shen X, Orkin SH. (2009) Glimpses of the epigenetic landscape. Cell Stem Cell. 4(1): 1-2.

32.Orkin SH, Wang J, Kim J, Chu J, Rao S, Theunissen TW, Shen X, Levasseur DN. (2008) The transcriptional network controlling pluripotency in ES cells. Cold Spring Harb Symp Quant Biol. 73: 195-202.

33.Shen X, Liu Y, Hsu Y, Fujiwara Y, Kim J, Mao X, Yuan G, and Orkin SH. (2008) EZH1 mediates methylation on histone H3 lysine 27 and complements EZH2 in maintaining stem cell identity and executing pluripotency. Mol Cell. 32(4):491-502.

· Previewed by Lena Ho and Gerald R. Crabtree. An EZ mark to miss. Cell Stem Cell. 2008. 3(6):577-8.

34.Kim J, Chu J, Shen X, Wang J, Orkin SH. (2008) An extended transcriptional network for pluripotency of embryonic stem cells. Cell. 132(6): 1049-61.

35.Wang J, Rao S, Chu J, Shen X, Levasseur DN, Theunissen TW, Orkin SH. (2006) A protein interaction network for pluripotency of embryonic stem cells. Nature. 444(7117):364-8.

36.Zhang K, Shen X, Wu J, Sakaki K, Saunders T, Rutkowski DT, Back SH, Kaufman RJ. (2006) Endoplasmic reticulum stress activates cleavage of CREBh to induce a systemic inflammatory response. Cell. 124(3): 587-99.

37.Shen X, Ellis RE, Sakaki K and Kaufman RJ. (2005) Genetic interactions due to constitutive and inducible gene regulation mediated by the unfolded protein response in C. elegans. PLoS Genetics. 1(3): e37.

38.Shen X, Zhang K, and Kaufman RJ. (2004) The unfolded protein response - a stress signaling pathway of the endoplasmic reticulum. J Chem Neuroanat. 28(1-2):79-92.

39.Lee K, Tirasophon W, Shen X, Michalak M, Prywes R, Okada T, Yoshida H, Mori K, and Kaufman RJ. (2002) IRE1-mediated unconventional mRNA splicing and S2P-mediated ATF6 cleavage merge to regulate XBP1 in signaling the unfolded protein response. Genes Dev. 16: 452-466.

40.Kaufman RJ, Scheuner D, Schroder M, Shen X, Lee K, Liu C and Arnold SM. (2002) The unfolded protein response in nutrient sensing and differentiation. Nat Rev Mol Cell Biol. 3(6):411-21.

41.Shen X, Ellis RE, Lee K, Liu C, Yang K, Solomon A, Yoshida H, Morimoto R, Kurnit DM, Mori K, and Kaufman RJ. (2001) Complementary signaling pathways regulate the unfolded protein response and are required for C. elegans development. Cell. 107: 893-903.

42.Norris SR, Shen X, and DellaPenna D. (1998) Complementation of the Arabidopsis pds1 mutation with the gene encoding p-Hydroxyphenylpyruvate Dioxygenase. Plant Physiol. 117(4): 1317 –1323.