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教师简介

陈亮
作者:管理员 来源:澳门新葡亰手机版 时间:2018-03-08 14:21:17 阅读量:
     

职称职务:研究员、博导
Appointment: Principle Investigator
学科专业:生物化学与分子生物学
Department: Biochemistry and Molecular Biology
研究方向:转录调控与基因组稳定性维持
Research: Transcription Regulation and Genome Integrity
实验室位置:澳门新葡亰大楼6016房间
Lab Location: College of Life Sciences, RM 6016
Email: liang_chen@whu.edu.cn





学习经历/Education:
1999.09 - 2003.06  浙江大学澳门新葡亰    学士   生物技术

           Zhejiang University    B.S.   Biotechnology

2003.09 - 2006.06  浙江大学澳门新葡亰    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   澳门新葡亰手机版             研究员
           College of Life Sciences, Wuhan University PI



研究内容/Research Summary:
  
基因表达是生成RNA与蛋白质的基础与前提,对发育、代谢等各个生命活动和疾病的发生、发展都起着核心作用,是分子生物学的重要领域,其研究对于生物医学的发展和药物开发都具有重大意义。我们主要运用分子生物学与生物化学、基因组学和生物信息学等多学科手段进行基因表达调控的机制研究。主要研究成果包括:1)发现基因转录过程中形成的特殊DNA/RNA杂合链结构R-loop与转录复合体的暂停/释放过程密切偶联,揭示了转录活性对R-loop的动态调控作用;2)发现RNA结合蛋白通过直接影响转录复合体活性或与表观遗传机制偶联实现对转录的调控作用,并发现若干RNA结合蛋白的突变干扰了转录行为,进而诱发DNA复制压力和基因组稳定性下降,最终促使癌症,如白血病的发生;3)发展了新测序方法用于研究全基因组水平的R-loop动态变化,为转录调控研究提供了新的高通量技术。




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.








代表性论文:
1. 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. Nature Protocols, 2019, 14: 1661-1685 (#: co-corresponding author).

2.
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 (*: co-first author). Cover story and highlighted by Cancer Discov.

3.
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. (*: co-first author). Highlighted by Nat Rev Genet and Nat Methods.

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.

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. (*: co-first author). Highlighted by Cell Research.

6.
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.

7.
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.

8.
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.



9. 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.

10.
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.

11.
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.

12.
Chen, L., Meng, Q., Kao, W., and Xia, Y. IκB kinase β regulates epithelium migration during corneal wound healing. Plos one, 2011, 6: e16132.

13.
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.

14.
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.

15.
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.

16.
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.

17.
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.

18.
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.




19.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. 




20. 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.


招生招聘:
热诚欢迎对功能基因组学、转录调控及相关疾病研究有兴趣的本科生、硕士/博士研究生和博士后加入。



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