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来源:亚傅体育app 时间:2018-03-08 14:21:17 阅读量:


Appointment: Principle Investigator
Department: Biochemistry and Molecular Biology
Research: Transcription Regulation and Genome Integrity
Lab Location: College of Life Sciences, RM 6015
Email: liang_chen@whu.edu.cn

1999.09 - 2003.06  浙江大学亚傅体育app    学士   生物技术

           Zhejiang University    B.S.   Biotechnology

2003.09 - 2006.06  浙江大学亚傅体育app    硕士   微生物

           Zhejiang University    M.S.   Microbiology

2006.09 - 2012.01  美国辛辛那提大学医学院   博士   环境遗传与分子毒理

           University of Cincinnati  Ph.D.   Environmental
           Genetics and Molecular Toxicology

工作经历与任职情况/Professional Experience:
2012.02 - 2018.02  美国加州大学圣地亚哥分校医学院        博士后

           University California San Diego      Postdoctoral Scholar

2018.02 - 至今    亚傅体育app             研究员
           College of Life Sciences, Wuhan University    PI

研究内容/Research Summary:

Gene expression, which includes transcription and post-transcriptional RNA processing, lays the foundation to direct diverse cellular functions in development and disease progression. Our laboratory is mainly interested in exploring the molecular basis for gene expression control in relation to disease development, such as cancer. Major projects include:

1) Inter-relationship between transcription and R-loop structure

R-loop is a three-stranded nucleic acid structure formed by hybridization of the newly transcribed RNA with the template DNA strand, leaving the non-template DNA strand displaced. Such a unique structure is widely present in the genome from bacterial to mammalian cells. R-loop is found to be involved in transcription regulation, epigenetic modulation and DNA replication, and its dysregulation is often linked to human diseases, such as cancers and neurodegenerative diseases. Our work reveals an intimate spatial-temporal association of R-loop level with transcriptional pause-release and suggests a direct role of RNA polymerase activity in regulating R-loop formation and resolution (Mol Cell, 2017). Disruption of R-loop dynamics by interfering transcription pause-release is further found to cause DNA replication stress and genome instability, which is a hidden disease mechanism for RNA binding protein mutations associated leukemia (Mol Cell, 2018).  

2) Multi-layer regulation of gene expression by RNA binding proteins and epigenetic regulators

Transcription is a complex process that is tightly regulated by cis-regulatory elements and trans-acting factors. We have identified that RNA binding proteins, in addition to its classical roles in mediating RNA processing, often work on chromatin to fine-tune transcription, either through directly modulating RNA polymerase activity (Mol Cell, 2018) or coordinating with epigenetic regulators (Mol Cell, 2016). These series of work indicate there exists a delicate network and multiple feedback mechanisms to ensure accurate transcription activity.

3) Development of new sequencing methods for functional genomics study

Fast accumulation of our knowledge in gene regulation is largely attributed to the development of functional genomics and various next-generation sequencing techniques. We have developed a new genome-wide method to map R-loop in human cells with high-resolution (Nat Protocols, 2019), which enables us to discover its role in transcription regulation and maintenance of genome integrity (Mol Cell, 2017, 2018). Further effort will be devoted to establish new methods in monitoring transcription and other molecular functions on chromatin.


Representative Publications (*: Co-corresponding Authors, #: Co-first Authors):

1.Zhang, M., Lai, Y., Krupalnik, V., Guo, P., Guo, X., … , Chen, L.*, Hanna, JH.*, Esteban, MA.* β-Catenin safeguards the ground state of mouse pluripotency by strengthening the robustness of the transcriptional apparatus. Sci Adv, 2020, 6: eaba1593

2.Chen, J-Y., Zhang, X., Fu X-D.* and Chen, L.* R-ChIP for genome-wide mapping of R-loops by using inactive RNase H. Nat Protoc, 2019, 14: 1661-1685.

3.Chen, L.#, Chen, J-Y.#, Huang, Y-J.#, Gu, Y., Qiu, J., Qian, H., Shao, C., Hu, J., Zhang, X., He, S., Zhou, Y., Li, H., Omar A-W, Zhang, D-E. and Fu, X-D. Augmented R-loop is a unifying mechanism for myelodysplastic syndromes induced by high risk splicing factor mutations Mol Cell, 2018, 69: 412-425. Cover story and highlighted by F1000 and Cancer Discov (doi: 10.1158/2159-8290.CD-RW2018-025).

4.Chen, L.#, Chen, J-Y.#, Zhang, X., Gu, Y., Xiao, R., Shao, C., Tang, P., Qian, H., Luo, D., Li, H., Zhou, Y., Zhang, D-E. and Fu, X-D. R-ChIP using inactive RNase H reveals dynamic coupling of R-loops with transcriptional pausing at gene promoters. Mol Cell, 2017, 68: 745-757. Highlighted by Nat Rev Genet (doi:10.1038/nrg.2017.98) and Nat Methods (doi:10.1038/nmeth.4572).

5.Wei, C.#, Xiao, R.#, Chen, L.#, Cui, H.#, Zhou, Y.#, Xue, Y., Hu, J., Zhou, B., Tsutsui, T., Qiu, J., Li, H., and Fu, X-D. RBFox2 Binds Nascent RNA to globally regulate polycomb complex 2 targeting in mammalian genomes. Mol Cell, 2016, 62: 875-889. Highlighted by F1000.

6.Chen, L., Peng, Z., Meng, Q., Mongan, M., Wang, J., Sartor, M., Chen, J., Niu, L., Medvedovic, M., Kao, W., and Xia, Y. Loss of IκB kinase β promotes myofibroblast transformation and senescence through activation of the ROS-TGFβ autocrine loop. Protein Cell, 2016, 7: 338-350.

All Publications:

1.Li, H., Wei, X., Zhou, L., Zhang, W., Wang, C., … , Yuan, Y., Chen, L., Wang, Q., Qu, J., Shen, Y., Liu, S., Fan, G., Liu, L., Liu, X., Hou, Y., Liu, GH.*, Gu, Y.*, Xu, X.* Dynamic cell transition and immune response landscapes of axolotl limb regeneration revealed by single-cell analysis. Protein Cell, 2020, Online ahead of print.

2.Zhang, C., Chen, L., Peng, D., Jiang, A., He, Y., Zeng, Y., Xie, C., Zhou, H., Luo, X., Liu, H., Chen, L., Ren, J., Wang, W., Zhao, Y. METTL3 and N6-Methyladenosine Promote Homologous Recombination-Mediated Repair of DSBs by Modulating DNA-RNA Hybrid Accumulation. Mol Cell, 2020, 79: 425-442.

3.Wu. T., Li, L., Jiang, X., Yang, Y., Song, Y., Chen, L., Xu, X., Shen, Y., Gu, Y. Sequencing and comparative analysis of three Chlorella genomes provide insights into strain-specific adaptation to wastewater. Sci Rep, 2019, 9: 9514.

4.Li, X., Zhou, B., Chen, L., Gou, L., Li, H. and Fu, X-D. GRID-seq reveals the global RNA-chromatin interactome. Nat Biotechnol, 2017, 35: 940-950. Cover story and highlighted by Nat Rev Genet (doi:10.1038/nrg.2017.81).

5.Chen, L., Mongan, M., Meng, Q., Wang, Q., Kao, W., and Xia, Y. Corneal wound healing requires IκB kinase β signaling in keratocytes. Plos One, 2016, 11: e0151869.

6.Qiu, J., Zhou, B., Thol, F., Zhou, Y., Chen, L., Shao, C., DeBoever, C., Hou, J., Li, H., Chaturvedi, A., Ganser, A., Bejar, R., Zhang, D-E., Fu, X-D. and Heuser, M. Distinct splicing signatures affect converged pathways in myelodysplastic syndrome patients carrying mutations in different splicing regulators. RNA, 2016, 22:1535-1549.  

7.Wang, L., Zhou, Y., Xu, L., Xiao, R., Lu, X., Chen, L., Chong, J., Li, H., He, C., Fu, X-D. and Wang, D. Molecular basis for RNA polymerase II to sense DNA methylation status during elongation. Nature, 2015, 523: 621-625.

8.Komeno, Y., Huang, Y-J., Qiu, J., Lin, L., Xu, Y., Zhou, Y., Chen, L., Monterroza, D., Li, H., DeKelver, R., Yan, Ming., Fu, X-D., and Zhang, D-E. SRSF2 is essential for hematopoiesis and its myelodysplastic syndromes-related mutations dysregulate alternative pre-mRNA splicing. Mol Cell Biol, 2015, 35: 3071-3082.

Before 2012:

9.Wang, J., Chen, L., Ko, CI., Zhang, L., Puga, A., and Xia, Y. Distinct signaling properties of mitogen-activated protein kinase kinases 4 (MKK4) and 7 (MKK7) in embryonic stem cell (ESC) differentiation. J Biol Chem, 2012, 287(4):2787-2797.

10.Chen, L., Meng, Q., Kao, W., and Xia, Y. IκB kinase β regulates epithelium migration during corneal wound healing. Plos one, 2011, 6: e16132.

11.Meng, Q., Peng, Z., Chen, L., Si, J., Dong, Z., and Xia Y. Nuclear factor-κB modulates cellular glutathione and prevents oxidative stress in cancer cells. Cancer Lett, 2010, 299: 45-53.

12.Peng, Z., Geh, E., Chen, L., Meng, Q., Fan, Y., Sartor, M., Shertzer, HG., Liu, ZG., Puga, A., and Xia, Y. Inhibitor of kappaB kinase beta regulates redox homeostasis by controlling the constitutive levels of glutathione. Mol Pharmacol, 2010, 77: 784-792.

13.Chen, L., Ovesen, JL., Puga, A., and Xia, Y. Distinct contribution of JNK and p38 to chromium cytotoxicity and inhibition of murine embryonic stem cell differentiation. Environ Health Perspect, 2009, 117: 1124-1130.

14.Mongan, M., Tan, Z., Chen, L., Peng, Z., Dietsch, M., Su, B., Leikauf, G., and Xia, Y. Mitogen-activated protein kinase kinase kinase 1 protects against nickel-induced acute lung injury. Toxicol Sci, 2008, 104: 405-411.

15.Takatori, A., Geh, E., Chen, L., Zhang, L., Meller, J., and Xia, Y. Differential transmission of MEKK1 morphogenetic signals by JNK1 and JNK2. Development, 2008, 135: 23-32.

16.Du, Z., Jin, B., Liu, W., Chen, L., and Chen, J. Highly sensitive fluorescent-labeled probes and glass slide hybridization for the detection of plant RNA viruses and a viroid. Acta Biochim Biophys Sin (Shanghai), 2007, 39: 326-334.

17.Chen, L., Chen, JS., Zhang, H., and Chen, SN. Complete nucleotide sequences of three dsRNA segments from Raphanus sativus-root cv. Yidianhong [corrected] with leaf yellow edge symptoms. Arch of Virol, 2006, 151: 2077-2083.  

18.Chen, L., Chen, JS., Liu, L., Yu, X., Yu, S., Fu, TZ., and Liu, WH. Complete nucleotide sequences and genome characterization of double-stranded RNA 1 and RNA 2 in the Raphanus sativus-root cv. Yidianhong [corrected]. Arch of Virol, 2006, 151: 849-859.