羅卓娟教授，博士生導(dǎo)師
羅卓娟，三級(jí)教授，青年首席教授，博士生導(dǎo)師，國(guó)家級(jí)青年人才。主要研究方向：表觀遺傳學(xué)、細(xì)胞生物學(xué)、癌癥生物學(xué)。主要研究?jī)?nèi)容：1、基因表達(dá)調(diào)控機(jī)制；2、基因印記調(diào)控機(jī)制；3、表觀遺傳與疾病發(fā)生發(fā)展。在Nature Cell Biology、Molecular Cell、Genes & Development、Nature Reviews Molecular Cell Biology、Science Advances、Nature Communications、Cell Death and Differentiation、等雜志發(fā)表SCI論文20余篇，引用3000余次。主持國(guó)家重點(diǎn)研發(fā)計(jì)劃（課題）、國(guó)家自然基金面上項(xiàng)目、江蘇省杰出青年基金、江蘇省“雙創(chuàng)人才”等項(xiàng)目。
教育和工作簡(jiǎn)歷：
1998至2002年，安徽大學(xué)，學(xué)士
2002至2005年，東南大學(xué)，碩士
2006至2011年，新加坡國(guó)立大學(xué)，博士
2011至2015年，美國(guó)Stowers Institute for Medical Research，博士后
2015年， Feinberg School of Medicine, Northwestern University，博士后
2016至今，東南大學(xué)，生命科學(xué)與技術(shù)學(xué)院，教授
研究方向：
1. 【染色質(zhì)結(jié)構(gòu)調(diào)控基因表達(dá)的功能機(jī)制】
DNA包裹組蛋白形成的染色質(zhì)結(jié)構(gòu)是基因表達(dá)的基本元件。染色質(zhì)表觀遺傳狀態(tài)和轉(zhuǎn)錄活性受到轉(zhuǎn)錄因子、表觀修飾因子、基因組序列和結(jié)構(gòu)等方面的嚴(yán)格調(diào)控?；蚪M二級(jí)結(jié)構(gòu)，包括非B型DNA結(jié)構(gòu)G4和R-loop，在遺傳信息表達(dá)中起關(guān)鍵調(diào)控性作用。G4與R-loop的異常累積可導(dǎo)致轉(zhuǎn)錄起始和延伸障礙、染色質(zhì)不穩(wěn)定、DNA復(fù)制異常，進(jìn)而造成細(xì)胞功能紊亂、胚胎發(fā)育異常及相關(guān)人類(lèi)疾病。研究其特異性調(diào)控對(duì)于理解不同細(xì)胞間的轉(zhuǎn)錄調(diào)控和命運(yùn)切換具有重要意義。實(shí)驗(yàn)室在國(guó)際上首次鑒定了ZEBRA (ZNF281，BRCA2，EMSY，QSER1)復(fù)合物，其通過(guò)維持染色質(zhì)的DNA-RNA雜交三鏈結(jié)構(gòu)R-loop（R環(huán)）動(dòng)態(tài)平衡，影響基因轉(zhuǎn)錄和DNA復(fù)制，介導(dǎo)干細(xì)胞多能性。實(shí)驗(yàn)室將繼續(xù)致力于染色質(zhì)結(jié)構(gòu)介導(dǎo)基因轉(zhuǎn)錄調(diào)控的機(jī)制探究，及其如何影響疾?。ò[瘤等）發(fā)生發(fā)展。
2.【表觀遺傳與基因組印記調(diào)控新機(jī)制探究】
基因組印記是一種非孟德?tīng)柺降奶厥膺z傳現(xiàn)象，受印記調(diào)控的基因（印記基因）呈父或母源特異性單拷貝表達(dá)。印記基因?qū)τ趥€(gè)體的生長(zhǎng)發(fā)育起到至關(guān)重要的作用，其異常會(huì)導(dǎo)致嚴(yán)重的多器官發(fā)育缺陷、智力障礙以及惡性腫瘤，如Angelman綜合征、Beckwith-Wiedemann 綜合征及Prader-Willi 綜合征。一直以來(lái)，表觀遺傳，包括DNA甲基化以及組蛋白H3K9甲基化，是調(diào)控基因組印記的唯一且經(jīng)典機(jī)制。實(shí)驗(yàn)室前期的研究在國(guó)際上首次發(fā)現(xiàn)轉(zhuǎn)錄延伸因子AFF3可結(jié)合在抑制性的甲基化印記控制區(qū)ICR，與表觀遺傳機(jī)器互作，雙向調(diào)控印記控制區(qū)ICR與增強(qiáng)子，以維持正確的基因組印記狀態(tài)。
實(shí)驗(yàn)室將進(jìn)一步探究表觀遺傳與基因組印記調(diào)控的新機(jī)制，探究增強(qiáng)子如何與ICR及表觀調(diào)控網(wǎng)絡(luò)互作，并結(jié)合多種疾病與發(fā)育模型中來(lái)探索基因組印記與X染色體失活的調(diào)控機(jī)制，為印記基因參與重大疾病發(fā)生發(fā)展提供新思路與新認(rèn)識(shí)。
3.【表觀遺傳與疾病發(fā)生發(fā)展】
癌癥等疾病的產(chǎn)生是諸多遺傳因素共同作用的結(jié)果，除了基因突變外，表觀遺傳學(xué)變化導(dǎo)致的轉(zhuǎn)錄調(diào)控遺傳也被認(rèn)為是癌癥產(chǎn)生的重要因素。研究癌癥表觀遺傳調(diào)控，可以溯源癌癥的發(fā)生過(guò)程、指針癌癥的惡性程度、尋找癌癥新的治療靶標(biāo)。實(shí)驗(yàn)室前期發(fā)現(xiàn)ZEBRA復(fù)合物通過(guò)轉(zhuǎn)錄調(diào)控、表觀遺傳修飾調(diào)控等多種方式影響惡性腫瘤疾病進(jìn)程。我們將進(jìn)一步探究表觀遺傳調(diào)控異常和疾病發(fā)生發(fā)展的關(guān)系，以期尋找潛在的癌癥分子治療靶標(biāo)。
代表性論文：（?通訊作者）
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 na?ve 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. （同期雜志述評(píng)）
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. （同期雜志述評(píng)）
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.
