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Xiaohua SHEN


Xiaohua SHEN



Lab website:http://xstem.med.tsinghua.edu.cn/?lang=zh 

Research Area:

Our research is aimed at understanding the role of chromatin structure in influencing gene expression and cell fate specification. The major portion of our research is to elucidate how epigenetic mechanisms are guided by and interact with lineage-specific factors, including proteins and/or non-coding ncRNAs to define cellular states in development and disease. We use state-of-art, high-throughput and integrative technologies across proteomic and genomic systems, together with mouse genetics, biochemical, molecular, cell biology and imaging tools to investigate the recruitment and regulation of PRC2 in stem and cancer cells. We aim to obtain a comprehensive and dynamic view of how transcription factors, ncRNAs and DNA motifs collaborate in targeting and regulating PRC2 during stem cell differentiation, and how disregulation in the above processes leads to human disease, particularly cancer.


Research interests include:
1. Epigenetic regulation in stem cell pluripotency and oncogenesis;
2. Long non-coding RNA in stem cell and cancer biology;
3. Chromatin structure in gene regulation.


Selected Publications:

1.     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. 16:1-13.

• Recommended in F1000Prime as being of special significant in its field by F1000 Faculty Member.

2.      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). Sox2-Dependent Functions of Tex10 in Epigenetic Control of the Super-Enhancer Activity for Pluripotency and Reprogramming. Cell Stem Cell. 16(6):653-68.

3.      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.

4.      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.

5.      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.

6.      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.

7.      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.

8.      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.139(7): 1303-1314.

9.      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.

10.    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.

11.   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.

12.   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 responseCell. 124(3): 587-99.

13.   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.

14.   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.







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