2011 – present Assistant investigator, Tsinghua-Peking Center for Life Sciences, Beijing, China
2010 – present Associate professor, 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
1999 - 2003 Ph.D. in Biological Chemistry with Randal Kaufman, University of Michigan School of Medicine, USA
1992 - 1996 B.S. in Biochemistry, Nankai University, Tianjin, China
About 80% of mammalian genomes are transcribed despite less than 2% encodes protein-coding genes. The fact that metazoans have a relatively common set of protein-coding genes despite various genome sizes suggests that morphologic complexity may positively correlate regulation complexity of gene expression. In addition, it is intriguing how distinct, cell type-specific epigenetic and gene expression programs are established de novo during development despite the same genetic blueprint and a similar set of epigenetic machinery.
We are interested in understanding 1) how the noncoding portions of the genome, including thousands of long non-code RNA (lncRNA) transcripts, help to shape epigenetic landscapes and regulate gene expression; and 2) how epigenetic mechanisms are guided by and interact with lineage-specific factors, including proteins and/or lncRNAs, to define cellular states in development and disease. We mainly use embryonic stem cells (ESCs) as a cell culture model to characterize epigenetic networks centered on protein-DNA-RNA interactions during ESC differentiation towards different lineages and to understand transcription regulations mediated by transcription factors, epigenetic regulators, lncRNAs and RNA-binding proteins in cell-fate determination.
Our work will elucidate fundamental aspects of chromatin and stem cell biology, provide an important framework in which to consider transcription regulations at the molecular and systems levels in normal mammalian development and disease, and perhaps suggest innovative approaches for disease intervention and to assist manipulation of cell fates for regenerative medicine in future studies
1. Epigenetic regulation mediated by polycomb proteins;
2. Long non-coding RNA (lncRNA);
3. Chromatin structure and transcription regulation in cell-fate determination.
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. 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.
4. 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.
5. 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.
6. 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.
7.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.
8. 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.
9. 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.
10.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.
11.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.
12.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.
Email: xshen at tsinghua.edu.cn