学习经历/Education

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

2003.09 － 2006.06 　浙江大学UFC体育竞猜网　　　硕士　　 微生物

　　　　　　　　　　 Zhejiang University　　　   M.S　　  Microbiology

1999.09 － 2003.06　 浙江大学UFC体育竞猜网　　　学士　　 生物技术

　　　　　　　　　　 Zhejiang University　　　   B.S　　   Biotechnology

工作经历与任职情况/Professional Experience

2023.02 － 至今　　　UFC体育竞猜网|(中国)有限公司　　　　　　教授

　　　　　　　　College of Life Sciences, Wuhan University   Professor

2018.02 － 2023.01　　UFC体育竞猜网|(中国)有限公司　　 　　　研究员

　　　　　　　　College of Life Sciences, Wuhan University   PI

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

兼职

细胞稳态湖北省重点实验室成员

UFC体育竞猜网RNA生物学研究所成员

Frontiers in Genetics RNA专刊客座编辑

Molecular Plant, Communications Biology, Protein & cell等杂志审稿人

SpatioTemporal Omics Consortium时空组学联盟创始成员

主持课题项目

1.　国家自然科学基金面上项目（32171289）：R环结构动态调控在早期发育中的功能与机制研究， 2022.01-2025.12，主持

2.　国家重点研发计划"干细胞研究与器官修复"专项（2021YFA1100503）：中内胚层来源组织器官间互作对干细胞命运的转录调控，2021-2026，骨干

3.　国家自然科学基金面上项目（31970619）：H3K79甲基化调控转录延伸速率的机制及功能研究，2020.01-2023.12，主持

4.　湖北省自然科学基金重点类创新群体（2020CFA017）： RNA结合蛋白与神经系统疾病2020.03-2023.03，骨干

主要科研奖励和个人荣誉

2019　　　　　  湖北省人才项目

2009-2011　　　Ryan fellowship, University of Cincinnati, 美国

2009　　　　　  Carl C. Smith Graduate Student Award for Meritorious Research，美国毒理学协会

课程教学

2021 － 至今 分子生物学（本科）

2019 － 2020 人类遗传学进展（本科）

研究内容/Research Summary

　　运用细胞与分子生物学、基因组学、生物化学与生物信息学等多学科手段研究基因转录调控、基因组稳定性维持的分子机制，及其在发育/疾病中的作用。

1）基于新组学技术研究转录与R-loop在发育与疾病中的作用机制

　　基因转录为细胞基础生命活动之一。基因组核酸结构R-loop由转录产生，受细胞高度调控，在机体发育、肿瘤与神经退行性疾病等重大疾病发生过程中起重要作用。我们利用细胞和模式动物，通过新组学技术的开发与运用挖掘R-loop的动态调节机制，深入研究转录异常对R-loop调控与基因组稳定性的影响，探讨R-loop调节组织发育和肿瘤发生发展的分子基础。

2）基于转录调控细胞异质性的神经胶质瘤机理研究

　　转录调控的特征之一是时空特异性和细胞间的异质性，也是造成细胞分化和肿瘤异质性及耐药的重要原因之一。我们利用单细胞转录组、染色质可及性以及空间转录组学等新技术研究神经胶质瘤发生机理，从单细胞层面对比各细胞类型的转录和染色质功能调控特征，探讨肿瘤细胞可塑性、迁移和耐药的转录调控基础，助力挖掘肿瘤诊疗新靶标。

　　在《Science》、《Molecular Cell》、《Nature Protocols》、《Science Advances》、《Nature Biotechnology》、《Nature》等国际权威学术期刊发表研究论文近40篇。研究成果被《Science》、《Nature Review Genetics》、《Nature Methods》、《Cancer Discovery》等特约评论。

发表的论文

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

1. Wei, X., Fu, S., Li, H., Liu, Y., Wang, S., Feng, W., Yang, Y., …, Liu, L., Chen, L.*, Xu, X.*, Fei, J-F.*, Gu Y.*. Single-cell Stereo-seq reveals induced progenitor cells involved in axolotl brain regeneration. Science, 2022, 377, 1062. Cover Story and highlighted by Science and Nat Rev Genet.
2. Wang, X., Sun, Q., Wang, W., Liu, B.*, Gu, Y.*, Chen, L.*. Decoding key cell sub-populations and molecular alterations in glioblastoma at recurrence by single-cell analysis. Acta Neuropathol Commun, 2023, 11, 125.
3. Wei, X.^#, Li, H.^#, Du, J., Zeng, X., Xu, X.*, Chen, L.*, Gu Y.*. Re-exploring tissue regeneration by novel spatial transcriptomics technologies. Clin Transl Med, 2022, 12, e1127.4. Zhang, F., and Chen, L.* Molecular Threat of Splicing Factor Mutations to Myeloid Malignancies and Potential Therapeutic Modulations. Biomedicines, 2022, 10, 1972.
5. Xu, B., Zhang, C., Jiang, A.,… Zhou, Y., Chen, L.*, Sun, H*. Histone methyltransferase Dot1L recruits O-GlcNAc transferase to target chromatin sites to regulate histone O-GlcNAcylation. JBC, 2022, 298, 102115.
6. Lin, R., Zhong, X., Zhou, Y., Geng, H., Hu, Q., Huang, Z., Hu, J., Fu, X-D., Chen, L.*, Chen, J-Y*. R-loopBase: a knowledgebase for genome-wide R-loop formation and regulation. NAR, 2022, D303-D315.
7. 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.
8. 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.
9. 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 Cancer Discov.
10. 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 and Nat Methods.
11. 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 Cell Research.
12. 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:

13. Li, J.,Zhao, J., Gan, X., Wang, Y., Jiang, D., Chen, L., Wang, F., Xu, J., Pei, H., Huang, J. and Chen, X. The RPA-RNF20-SNF2H cascade promotes proper chromosome segregation and homologous recombination repair. Proc Natl Acad Sci U S A, 2023,120: e2303479120
14. Ba, H., Wang, X., Wang, D., Ren, J., Wang, Z., Sun, H. X., Hu, P., Zhang, G., Wang, S., Ma, C., Wang, Y., Wang, E., Chen, L., Liu, T., Gu, Y., Li, C. Single-cell transcriptome reveals core cell populations and androgen-RXFP2 axis involved in deer antler full regeneration. Cell Regen, 2022, 1:43.
15. Huang, Y-J., Chen, J-Y., Yan, M., Davis, A., Miyauchi, S., Chen, L., … Fu, X-D., and Zhang, D-E. RUNX1 deficiency cooperates with SRSF2 mutation to induce multilineage hematopoietic defects characteristic of MDS. Blood Adv, 2022, https://doi.org/10.1182/bloodadvances.2022007804
16. Wang, C., Xu, Q., Zhang, X., Day, D., Abraham, B., Lun, K., Chen, L., Huang, J., Ji, X. BRD2 interconnects with BRD3 to facilitate Pol II transcription initiation and elongation to prime promoters for cell differentiation. Cell Mol Life Sci, 2022, 79: 338
17. Wang, D., Wang, X., Ba, H., Ren, J., Wang, Z., Sun, H., Chen, L., Liu, C., Wang, Y., Li, J., Liu, L., Liu, T., Yang, Y., Liu, G-H., Gu, Y and Li, C. Chimeric blood vessels sustained development of the xenogeneic antler: a unique model for xenogeneic organ generation. Life Med, 2022, https://doi.org/10.1093/lifemedi/lnac021
18. Chen, J-Y. ^#, Lim, D-H. ^#, Chen L. ^#, Zhou Y., Zhang F., Shao C., Zhang X., Li H., Wang D., Zhang D-E., and Fu X-D. Systematic Evaluation of Different R-loop Mapping Methods: Achieving Consensus, Resolving Discrepancies and Uncovering Distinct Types of RNA:DNA Hybrids. BioRxiv, 2022, https://doi.org/10.1101/2022.02.18.480986
19. Wang, K. ^#, Wang, H. ^#, Li, C. ^#, Ying, Z., Xiao, R., Li, Q., Xiang, Y., Wang, W., Huang, J., Chen, L., Fang, P.*, Liang K.* Genomic Profiling of Native R-loops with a DNA-RNA Hybrid Recognition Sensor. Sci Adv, 2021, 7: eabe3516.
20. 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.
21. Li, H., Wei, X., Zhou, L., Zhang, W., Wang, C., Guo, Y., Li, D., Chen, J., Liu, T., Zhang, Y., Ma, S., Wang, C., Tan, F., Xu, J., Liu, Y., 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, 12: 57-66.
22. 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.
23. Huang, Y-J., Yan, M., Chen, J-Y., Chen, L., Kim, E., Shima, T., Davis, A. G., Miyauchi, S., Stoner, S. A., Fu, X-D., Abdel-Wahab, O. I., Zhang, D-E. RUNX1 Deficiency Cooperates with SRSF2 Mutation to Further Disrupt RNA Splicing and Exacerbate Myelodysplastic Syndromes in Mouse Models. Blood, 2018, 132:1796.
24. 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.
25. 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.
26. 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.
27. 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.
28. 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.
29. 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.
30. Chen, L., Meng, Q., Kao, W., and Xia, Y. IκB kinase β regulates epithelium migration during corneal wound healing. Plos one, 2011, 6: e16132.
31. 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.
32. 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.
33. 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.
34. 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.
35. 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.
36. 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.
37. Chen, L., Chen, JS., Zhang, H., and Chen, SN. Complete nucleotide sequences of three dsRNA segments from Raphanus sativus-root cv. Yidianhong with leaf yellow edge symptoms. Arch of Virol, 2006, 151: 2077-2083.
38. 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. 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。