Xiaohua Shen Ph.D.

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
2009 Claudia Adams Barr Program Award in Cancer Research, USA
2002 Adam and Mary J. Chrisman Award, University of Michigan, USA

Main Research Fields

Our main research interest is to understand how the noncoding portions of the genome, particularly noncoding RNAs (ncRNAs) and genomic repeats, act with their associated proteins to shape distinct epigenetic and cellular states during stem-cell differentiation and in development. In the past years, we have rigorously investigated novel aspects of ncRNAs, genomic repeats, and RNA-binding proteins in transcription and chromatin regulation in mouse embryonic stem cells and embryos, and revealed important paradigms of noncoding RNA-mediated regulation in transcription and chromatin structure. We will continue to elucidate the regulation and function of noncoding RNA, RBPs and genomic repeats at the molecular and systems levels by using high-throughput integrative approaches across proteomic and genomic systems, together with state-of-art single-cell, imaging, biochemical, and mathematical techniques. Our work will help to elucidate fundamental aspects of chromatin and developmental biology, and provide an important framework in which to consider transcription control and cell-fate determination in normal 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. The structure and function of the cell nucleus

2. The noncoding genomes and cell-fate programs

3. Physical modeling and the virtual nucleus

KEY WORDS

noncoding genome, transposons, ncRNA, RNA metabolism, transcription, chromatin organization, stem-cell pluripotency, embryonic development, cell-fate determination, physical modeling

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.          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. (* cocorresponding).

3.          Yin Y*, Lu JY, Zhang X, Shao W, Xu Y, Li P, Hong Y, Cui L, Shan G, Tian B, Zhang Q, Shen X*. U1 snRNP regulates chromatin retention of noncoding RNAs. Nature. 2020. 580(7801):147-150. (* 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.          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. Genomic repeats categorize genes with distinct functions for orchestrated regulation. (2020). Cell Reports. 30(10):3296-3311.

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

7.          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*. The lncRNA Hand2os1/Uph locus orchestrates heart development through regulation of precise expression HAND2. Development. 2019. 146, dev176198. (* co-corresponding)

8.          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. RNA targets ribosome biogenesis factor WDR43 to chromatin for transcription and pluripotency control. Mol Cell. 2019. 75: 102-116.

9.          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*. Insight into novel RNA-binding activities via large-scale analysis of lncRNA-bound proteome and IDH1-bound transcriptome. Nucleic Acids Res. 2019. 47(5): 2244-2262. (*co-corresponding)

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

11.      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*. Mouse knockout models reveal largely dispensable but context-dependent functions of lncRNAs during development. 2018. J Mol Cell Biol. 10(2):175-178. (* co-corresponding)

12.      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. Divergent lncRNAs regulate gene expression and lineage differentiation in pluripotent cells. Cell Stem Cell. 2016. 18(5):637-52.

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

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