罗卓娟教授,博士生导师
罗卓娟,三级教授,青年首席教授,博士生导师,国家级青年人才。主要研究方向:表观遗传学、细胞生物学、癌症生物学。主要研究内容:1、基因表达调控机制;2、基因印记调控机制;3、表观遗传与疾病发生发展。在Nature Cell Biology、Molecular Cell、Genes & Development、Nature Reviews Molecular Cell Biology、Science Advances、Nature Communications、Cell Death and Differentiation、等杂志发表SCI论文20余篇,引用3000余次。主持国家重点研发计划(课题)、国家自然基金面上项目、江苏省杰出青年基金、江苏省“双创人才”等项目。
教育和工作简历:
1998至2002年,安徽大学,学士
2002至2005年,东南大学,硕士
2006至2011年,新加坡国立大学,博士
2011至2015年,美国Stowers Institute for Medical Research,博士后
2015年, Feinberg School of Medicine, Northwestern University,博士后
2016至今,东南大学,生命科学与技术学院,教授
研究方向:
1. 【染色质结构调控基因表达的功能机制】
DNA包裹组蛋白形成的染色质结构是基因表达的基本元件。染色质表观遗传状态和转录活性受到转录因子、表观修饰因子、基因组序列和结构等方面的严格调控。基因组二级结构,包括非B型DNA结构G4和R-loop,在遗传信息表达中起关键调控性作用。G4与R-loop的异常累积可导致转录起始和延伸障碍、染色质不稳定、DNA复制异常,进而造成细胞功能紊乱、胚胎发育异常及相关人类疾病。研究其特异性调控对于理解不同细胞间的转录调控和命运切换具有重要意义。实验室在国际上首次鉴定了ZEBRA (ZNF281,BRCA2,EMSY,QSER1)复合物,其通过维持染色质的DNA-RNA杂交三链结构R-loop(R环)动态平衡,影响基因转录和DNA复制,介导干细胞多能性。实验室将继续致力于染色质结构介导基因转录调控的机制探究,及其如何影响疾病(包括肿瘤等)发生发展。
2.【表观遗传与基因组印记调控新机制探究】
基因组印记是一种非孟德尔式的特殊遗传现象,受印记调控的基因(印记基因)呈父或母源特异性单拷贝表达。印记基因对于个体的生长发育起到至关重要的作用,其异常会导致严重的多器官发育缺陷、智力障碍以及恶性肿瘤,如Angelman综合征、Beckwith-Wiedemann 综合征及Prader-Willi 综合征。一直以来,表观遗传,包括DNA甲基化以及组蛋白H3K9甲基化,是调控基因组印记的唯一且经典机制。实验室前期的研究在国际上首次发现转录延伸因子AFF3可结合在抑制性的甲基化印记控制区ICR,与表观遗传机器互作,双向调控印记控制区ICR与增强子,以维持正确的基因组印记状态。
实验室将进一步探究表观遗传与基因组印记调控的新机制,探究增强子如何与ICR及表观调控网络互作,并结合多种疾病与发育模型中来探索基因组印记与X染色体失活的调控机制,为印记基因参与重大疾病发生发展提供新思路与新认识。
3.【表观遗传与疾病发生发展】
癌症等疾病的产生是诸多遗传因素共同作用的结果,除了基因突变外,表观遗传学变化导致的转录调控遗传也被认为是癌症产生的重要因素。研究癌症表观遗传调控,可以溯源癌症的发生过程、指针癌症的恶性程度、寻找癌症新的治疗靶标。实验室前期发现ZEBRA复合物通过转录调控、表观遗传修饰调控等多种方式影响恶性肿瘤疾病进程。我们将进一步探究表观遗传调控异常和疾病发生发展的关系,以期寻找潜在的癌症分子治疗靶标。
代表性论文:(†通讯作者)
1. Xie P*, Zhu S*, Zhang J*, Wang X, Jiang X, Xiong F, Chen L, Fang K, Ji Y, Zheng B, Da L, Cao H, Sun Y†, Luo Z†, Lin C†. 4D live tracing reveals distinct movement trajectories of meiotic chromosomes. Life medicine, 2024 Aug (Accepted).
2. Xie P*, Jiang X*, He J*, Pan Q*, Yang X*, Zheng Y*, Fan W, Wu C, Zheng W, Fang K, Si S, Zhu S, Yang Y, Zhong T, Yang Z, Wei K, Xie W, Jing N†, Luo Z†, Lin C†.Epigenetic delineation of the earliest cardiac lineage segregation by single-cell multi-omics. Elife. 2024 Jul:98293v1.
3. Mao G*, Yang Y*, Luo Z†, Lin C†,Xie P†. SpatialQC: transcriptome data automated quality control for spatial transcriptome data. Bioinformatics, 2024 Aug 2;40(8):btae458.
4. Meng S*, Liu X*, Zhu S*, Xie P*, Fang H, Pan Q, Fang K, Li F, Zhang J, Che Z, Zhang Q, Mao G, Wang Y, Hu P, Chen K, Sun F, Xie W, Luo Z†, Lin C†. Young LINE-1 transposon 5’UTRs marked by elongation factor ELL3 function as enhancers to regulate naïve pluripotency in embryonic stem cells. Nat Cell Biol. 2023 Sep;25(9):1319-1331.(封面文章)
5. Che Z*, Liu X*, Dai Q*, Fang K, Guo C, Yue J, Fang H, Xie P, Luo Z†, Lin C†. Distinct roles of the two SEC scaffold proteins, AFF1 and AFF4, in regulating RNA Pol II transcription elongation. J Mol Cell Biol. 2023 Aug 1:mjad049.
6. Guo C, Zhang Y, Shuai S, Sigbessia A, Hao S, Xie P, Jiang X, Luo Z†, Lin C†. The super elongation complex (SEC) mediates phase transition of SPT5 during transcriptional pause release. EMBO Rep. 2023 Jan 11:e55699. (同期杂志述评)
7. Guo C, Luo Z†, Lin C†. Phase Separation Properties in Transcriptional Organization. Biochemistry. 2022 Nov 15;61(22):2456-2460.
8. Zhao X*, Fang K*, Liu X, Yao R, Wang M, Li F, Hao S, He J, Wang Y, Fan M, Huang W, Li Y, Gao C, Lin C†, Luo Z†. QSER1 preserves the suppressive status of the pro-apoptotic genes to prevent apoptosis. Cell Death Differ. 2022 Nov 12.
9. Wang Y, Ma B, Liu X, Gao G, Che Z, Fan M, Meng S, Zhao X, Sugimura R, Cao H, Zhou Z, Xie J, Lin C†, Luo Z†. ZFP281-BRCA2 prevents R-loop accumulation during DNA replication. Nat Commun. 2022 Jun 17;13(1):3493.
10. Guo C, Luo Z†, Lin C†. Phase separation, transcriptional elongation control, and human diseases. J Mol Cell Biol. 2021 Aug 4;13(4):314-318. (封面文章)
11. Yue J, Dai Q, Hao S, Zhu S, Liu X, Tang Z, Li M, Fang H, Lin C†, Luo Z†. Suppression of the NTS-CPS1 regulatory axis by AFF1 in lung adenocarcinoma cells. J Biol Chem. 2021 Jan-Jun;296:100319.
12. Du H*, Chen C*, Wang Y, Yang Y, Che Z, Liu X, Meng S, Guo C, Xu M, Fang H, Wang F, Lin C†, Luo Z†. RNF219 interacts with CCR4-NOT in regulating stem cell differentiation. J Mol Cell Biol. 2020 Oct 26;12(11):894-905.
13. Guo C, Che Z, Yue J, Xie P, Hao S, Xie W, Luo Z†, Lin C†. ENL initiates multivalent phase separation of the super elongation complex (SEC) in controlling rapid transcriptional activation. Sci Adv. 2020 Apr 1;6(14):eaay4858.
14. Luo Z, Liu X, Xie H, Wang Y, Lin C †. ZFP281 recruits MYC to active promoters in regulating transcriptional initiation and elongation. Mol Cell Biol. 2019 Sep 30. pii: MCB.00329-19.
15. Zhang Y, Wang C, Liu X, Yang Q, Ji H, Yang M, Xu M, Zhou Y, Xie W, Luo Z, Lin C †. AFF3-DNA methylation interplay in maintaining the mono-allelic expression pattern of XIST in terminally differentiated cells. J Mol Cell Biol. 2018 Dec 7. (同期杂志述评)
16. Dai Q*, Shen Y*, Wang Y*, Wang X, Francisco JC, Luo Z, Lin C †. Striking a balance: regulation of transposable elements by Zfp281 and Mll2 in mouse embryonic stem cells. Nucleic Acids Res. 2017 Sep 25.
17. Francisco JC, Dai Q, Luo Z, Wang Y, Chong RH, Tan YJ, Xie W, Lee GH, Lin C †. Transcriptional elongation control of the HBV cccDNA transcription by Super Elongation Complex (SEC) and BRD4. Mol Cell Biol. 2017 Jul 10. pii: MCB.00040-17.(封面文章)
18. Wang Y*, Shen Y*, Dai Q, Yang Q, Zhang Y, Wang X, Xie W, Luo Z†, Lin C †. A permissive chromatin state regulated by ZFP281-AFF3 in controlling the imprinted Meg3 polycistron. Nucleic Acids Res. 2017 Feb 17;45(3):1177-1185.
19. Luo Z, Lin C†. Enhancer, epigenetics and human diseases. Curr Opin Genet Dev. 2016 Apr 21;36:27-33.
20. Luo Z, Lin C, Ashley RW, Bartom E, Gao X, Smith E, and Shilatifard A. Regulation of imprinted gene expression by allele-specific enhancer activity. Genes Dev. 2016 Jan 1;30(1):92-101.
21. Luo Z, Gao X, Lin C, Smith ER, Marshall SA, Swanson SK, Florens L, Washburn MP, Shilatifard A. Zic2 is an enhancer-binding factor required for embryonic stem cell specification. Mol Cell. 2015 Feb 19;57(4):685-94.
22. Lin C, Garrus AS, Luo Z, Guo F, Shilatifard A. The RNA Pol II elongation factor Ell3 marks enhancers in ES cells and primes future gene activation. Cell. 2013 Jan 17;152(1-2):144-56.
23. Luo Z, Lin C, Shilatifard A. The super elongation complex (SEC) family in transcriptional control. Nat Rev Mol Cell Biol. 2012 Aug 16;13(9):543-7.
24. Luo Z, Lin C, Guest E, Garrett AS, Mohaghegh N, Swanson S, Marshall S, Florens L, Washburn MP, Shilatifard A. The super elongation complex family of RNA polymerase II elongation factors: gene target specificity and transcriptional output. Mol Cell Biol. 2012 Jul;32(13):2608-17.