Molecular Cell Biology

Xiaohua SHEN Ph.D

Professor School of Basic Medical Sciences

Contact Us:
E-mail: xshen@tsinghua.edu.cn
Address:Rm D108, Tsinghua University Medical Science Building, Tsinghua University, Beijing 100084, China

Education:

1996 B.S. Biochemistry Nankai University, Tianjin, China2003 Ph.D. Biological Chemistry University of Michigan, Ann Arbor, USA (with Randal Kaufman)

Professional Positions:

2020- present Professor, School of Medicine, Tsinghua University

2017- present Yantz Professor of the Ministry of Education

2016- 2020 Associate professor (tenured), School of Medicine, Tsinghua University Associate investigator, Tsinghua-Peking Center for Life Sciences

2011- 2016 Assistant investigator, Tsinghua-Peking Center for Life Sciences

2010- 2016 Associate professor (tenure-track), School of Medicine, Tsinghua University

2009- 2010 Instructor in Pediatrics, Harvard Medical School, USA

2004- 2008 Postdoctoral fellow with Stuart Orkin, Dana-Farber Cancer Institute, Children’s Hospital Boston and Harvard Medical School, USA

Research Areas:

1. The structure and function of the cell nucleus

2. The noncoding genomes and cell-fate programs

3. Physical modeling and the virtual nucleus

Honors and Awards:

➢ 2021 Tan Jiazhen Life Sciences Innovation Award, China

➢ 2019 The National Science Fund for Distinguished Young Scholars, China

➢ 2016 Royan International Research Award, Iran

➢ 2013 QiuShi Foundation, Outstanding Young Scholar Award, China

➢ 2013 ‘221’ Outstanding Young Scholar, Tsinghua University, China

➢ 2011 & 2012 Bayer Investigator Awards, Tsinghua University, China

➢ 2009 Claudia Adams Barr Program Award in Cancer Research, USA

➢ 2002 Adam and Mary J. Chrisman Award, University of Michigan, USA

Selected Publications:

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.