AssistantInvestigator,NIBS,Beijing,ChinaPhone：010-80726688
Fax：010-80726689
E-mail：lixialu@nibs.ac.cn
教育经历Education2000中国科学院上海生物化学研究所分子生物学博士
Ph.D.degreeinmolecularbiologyShanghaiInstituteofBiochemistry,ChineseAcademyofSciences,P.R.China
1995复旦大学生物化学系生物化学学士
B.S.degreeinBiochemistryDepartmentofBiochemistry,Fu-DanUniversity,Shanghai,P.R.China
工作经历ProfessionalExperienceJune2006-中国北京生命科学研究所工作
NationalInstituteofBiologicalSciences,Beijing,China
2005-June2006美国哥伦比亚大学生物系助理研究员
AssociateResearchScientist
2000-2005美国哥伦比亚大学生物系博士后
Post-DoctoralResearchScientistDepartmentofBiologicalSciences,ColumbiaUniversityU.S.A.
研究概述：转录是生命不可或缺的重要生物学过程。然而，在过去的三十年中，越来越多的实验证据表明，转录也是生物体内引起基因组非稳性的主要原因之一。本实验室的主要研究兴趣在于运用遗传学，分子生物学，生物化学和生物信息学等方法，研究与转录相关的基因组非稳性，并探索这一机制的潜在病理意义。目前，我们的工作集中于：1.Rloop与基因组非稳性:Rloop是一种在转录过程中产生的由新生RNA链与模板DNA链配对形成的RNA:DNA杂合分子。我们之前的研究工作揭示，从细菌到人类细胞，这种RNA：DNA杂合分子的形成都会破坏基因组完整性。我们希望后续工作可以：a．解析哺乳动物细胞预防和解除R-loop结构的机制b．探究R-loop介导的基因组非稳性在人类疾病形成中的潜在的作用2.癌症基因组的进化：我们最近的一项研究结果表明转录失调可以导致人染色体特定区域稳定性下降。基因组非稳性和转录重编排与许多人类疾病密切相关，其中包括癌症。由上述工作引出的一个重要而有趣的问题是：转录是否在癌症基因组进化中扮演了重要但是尚未了解的角色。目前我们正在探索转录相关基因组非稳性在卵巢癌基因组变化中的作用。ResearchDescription:Transcriptionisafundamentalandineluctableprocessoflife.However,inthepastthreedecades,aconsiderablebodyofevidencehasestablishedthattranscriptionisoneofthekeycontributorstogenomeinstability.Themainresearchgoalofourlabistounderstandmolecularmechanism(s)andpathologicalrelevance(s)oftranscription-associatedgenomeinstabilityinmammaliancellsbyusingavarietyofgenetic,molecular,biochemicalandbioinformaticapproaches.Ourcurrentinterestsfocuson:1.Rloopandgenomeinstability:CotranscriptionlRloopisastructureinwhichanascenttranscriptishybridizedwiththetemplateDNAstrand,leavingthenon-templatestrandunpaired.OurpreviousstudieshaveestablishedthatsuchRNA:DNAhybridhasaninherentimpactontheintegrityofthegenomefrombacteriatomammals.Wearecurrentlyinterestedto:a.elucidatethemechanism(s)underlyingRloop-mediatedgenomeinstabilityb.dissectthemechanism(s)bywhichmammaliancellspreventandresolveRloopduringtranscriptionc.investigatethepathologicalconsequence(s)oftranscriptionalRloopformation2.Cancergenomeevolution:Oneofourrecentstudieshasestablishedastrikinglinkbetweentranscriptiondisorderandtheexpressionofchromosomefragilityinhumancells.Grosschromosomeabnormalityandtranscriptionreprogrammingarehallmarksofanumberofhumandiseases,includingcancer.Extendingfromtheabovestudy,wearecurrentlypursuingthepotentialrole(s)oftranscription-associatedgenomeinstabilityinovariancancergenomeevolution.Publications:1.YiWei*,FanYang*,JieLiu,YonggongZhaiandXialuLi,Rloopunderliestranscription-associatedchromosomefragilityinhumancells(*Theseauthorscontributeequally)(inpreparation)2.WenjianGan,ZhishuangGuanandXialuLi,ImpairmentofreplicationforkprogressionisanevolutionallyconservedmechanismunderlyingRloop-mediatedgenomeinstability.(inpreparation)3.XialuLiandJamesL.Manley,2009,TheRoleofAlternativeSplicingDuringtheCellCycleandProgrammedCellDeath.InRalphA.BradshawandEdwardA.Dennis,editors:HandbookofCellSignaling2ndedition,Oxford:AcademicPress,,pp.2329-2334.(invitedbookchapter)4.XialuLi*,TianhuiNiu.,andJamesLManley.2007.TheRNAbindingproteinRNPS1alleviatesASF/SF2depletion-inducedgenomicinstability.RNA13(12):2108-2115(*correspondingauthor).5.XialuLiandJamesLManley,2006,Co-transcriptionalprocessesandtheirinfluenceongenomestability.Genes&Development,2006;20(14):1838-1847.6.XialuLiandJamesLManley.2006.AlternativeSplicingandControlofApoptoticDNAFragmentation.CellCycle5(12).1286-12887.XialuLiandJamesL.Manley,2005,Newtalentsforanoldacquaintance:theSRproteinsplicingfactorASF/SF2functionsinthemaintenanceofgenomestability.Cellcycle,4(12):1706-1708.8.XialuLi,JinWangandJamesLManley,2005,LossofsplicingfactorASF/SF2inducesG2cell-cyclearrestandapoptosis,butinhibitsinternucleosomalDNAfragmentation,Genes&Development,19(22):2705-2714.9.XialuLiandJamesLManley,2005,InactivationoftheSRproteinsplicingfactorASF/SF2resultsingenomicinstability.Cell,122(3),p365-378.10.BoliangLi,XialuLietal.,1999,Humanacyl-CoA:Cholesterolacyltransferase-1(ACAT-1)geneorganizationandevidencethatthe4.3-kilobaseACAT-1mRNAisproducedfromtwodifferentchromosomes.,JBiolChem,274(16):p11060-11071
