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个人简介

2002年本科毕业于南开大学生命科学学院生物化学系; 2009年在中科院上海生物化学与细胞生物学研究所获博士学位; 2009年至2014年在美国国立卫生研究院糖尿病、消化道和肾脏疾病研究所(NIH/NIDDK)进行博士后研究工作; 2014年11月加入上海科技大学生命科学与技术学院任助理教授、研究员; 2019年10月晋升为上海科技大学生命科学与技术学院常任副教授、研究员。 2016年获得上海市科委浦江人才计划资助; 2018年获得国家自然科学基金委优秀青年科学基金资助; 2019年获得上海市生物化学与分子生物学会“青年新锐”奖。 目前承担国家自然科学基金委面上项目、优青项目、科技部重点研发计划等项目

研究领域

DNA修复、基因编辑与癌症发生

物种繁衍与基因组的稳定性密切相关,这在细胞内是由一系列精巧而复杂的DNA修复机制负责维持的。然而在某些生理、病理状态下细胞会激活错误倾向性DNA修复机制,因此DNA修复精确性和错误倾向性之间的平衡对于疾病发生、衰老和进化都具有重要的意义。 基因编辑指利用可设计的核酸酶通过碱基插入、缺失、置换等方式,对生物体基因组DNA特定片段进行改造从而达到对目标基因进行编辑的一种基因工程,可广泛应用于生命科学基础研究、生物技术开发、农业技术开发以及医药研发领域。传统的CRISPR/Cas基因编辑技术虽然具有较高的基因敲除效率,但在执行碱基替换时效率通常较低。近年内,将CRISPR/Cas与核酸脱氨酶整合发展出的碱基编辑系统,可在单碱基水平对基因组实现高效率的靶向性编辑改造。 我们实验室长期从事DNA修复以及基因编辑相关的研究工作,已阐明胞嘧啶脱氨酶APOBEC在CRISPR/Cas9介导的基因编辑过程中产生突变的分子机制,成功创建更高精度和更高效率的增强型Cas9碱基编辑器(eBE)、可在基因组A/T富集区域内开展有效编辑的Cpf1碱基编辑器(dCpf1-BE)、以及可在G/C富集区域和高甲基化区域内开展高效编辑的普适型Cas9碱基编辑器(hA3A-BE)。 未来几年中,我们实验室将进一步探索由DNA修复引发的突变在基因编辑、疾病发生以及衰老等过程中所起的作用,主要集中于以下几个方面:1)研究DNA修复在基因编辑过程中引发突变的分子机制;2)创建新型基因编辑系统;3)鉴定并分析DNA修复引发突变的新分子和新通路;4)探索DNA修复引发突变在癌症发生以及衰老过程中的作用。我们的研究将有助于发展新型基因编辑系统,揭示癌症发生的新机制以及完善衰老的DNA损伤学说

近期论文

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(#co-firstauthor,*correspondingauthor) 1.YingWang#,RunzeGao#,JingWu#,Yi-ChunXiong,JiaWei,SipinZhang,BeiYang,JiaChen*andLiYang*.ComparisonofcytosinebaseeditorsanddevelopmentoftheBEable-GPSdatabasefortargetingpathogenicSNVs.GenomeBiol,2019,20:218-224 2.JiaChen*,BeiYang*andLiYang*.ToBEornottoBE,thatisthequestion.NatBiotechnol,2019,37:520-522 3.BeiYang*,LiYang*andJiaChen*.DevelopmentandApplicationofBaseEditors.CRISPRJ,2019,2:91-104 4.JiananLi#,ZhenLiu#,ShishengHuang#,XiaoWang,GuangleiLi,YutingXu,WenxiaYu,ShanshanChen,YuZhang,HanhuiMa,ZunfuKe,JiaChen*,QiangSun*andXingxuHuang*.EfficientbaseeditinginG/C-richregionstomodelandrogeninsensitivitysyndrome.CellRes,2019,29:174-176 5.XiaoWang#,JiananLi#,YingWang#,BeiYang#,JiaWei#,JingWu,RuixuanWang,XingxuHuang*,JiaChen*andLiYang*.EfficientbaseeditinginmethylatedregionswithahumanAPOBEC3A-Cas9fusion.NatBiotechnol,2018,36:946-949(HighlightedbyNicoleRusk,Betterbaseeditors.NatMethods,2018,15:763) 6.YantingZeng#,JiananLi#,GuangleiLi#,ShishengHuang,WenxiaYu,YuZhang,DunjinChen,JiaChen,JianqiaoLiu*andXingxuHuang*.CorrectionoftheMarfanSyndromepathogenicFBN1mutationbybaseeditinginhumancellsandheterozygousembryos.MolTher,2018,26:2631-2637 7.ZhenLiu#,ZongyangLu#,GuangYang#,ShishengHuang,GuangleiLi,SongjieFeng,YajingLiu,JiananLi,WenxiaYu,YuZhang,JiaChen,QiangSun*andXingxuHuang*.EfficientgenerationofmousemodelsofhumandiseasesviaABE-andBE-mediatedbaseediting.NatCommun,2018,9:2338 8.WenJiang#,SongjieFeng#,ShishengHuang,WenxiaYu,GuangleiLi,GuangYang,YajingLiu,YuZhang,LeiZhang,YuHou,JiaChen,JiepingChen*andXingxuHuang*.BE-PLUS:anewbaseeditingtoolwithbroadenededitingwindowandenhancedfidelity.CellRes,2018,28:855-861 9.JiaChen,WeizhiJi,PrashantMaliandAprilPawluk.TheFutureofGenomeEditing.Cell,2018,173:1311-1313 10.XiaosaLi#,YingWang#,YajingLiu#,BeiYang#,XiaoWang,JiaWei,ZongyangLu,YuxiZhang,JingWu,XingxuHuang*,LiYang*andJiaChen*.Baseeditingwithacpf1-cytidinedeaminasefusion.NatBiotechnol,2018,36:324-327(HighlightedinToolsinBrief,Expandingtherangeofbaseeditors.NatMethods,2018,15:314) 11.LiqunLei#,HongquanChen#,WeiXue#,BeiYang#,BianHu#,JiaWei,LijieWang,YiqiangCui,WeiLi,JianyingWang,LeiYan,WanjingShang,JiminGao,JiahaoSha,MinZhuang,XingxuHuang,BinShen*,LiYang*andJiaChen*.APOBEC3inducesmutationsduringrepairofCRISPR–Cas9-generatedDNAbreaks.NatStructMolBiol,2018,25:45-52 12.LijieWang#,WeiXue#,LeiYan#,XiaosaLi,JiaWei,MiaomiaoChen,JingWu,BeiYang*,LiYang*andJiaChen*.Enhancedbaseeditingbyco-expressionoffreeuracilDNAglycosylaseinhibitor.CellRes,2017,27:1289-1292 13.GuangleiLi,YajingLiu,YantingZeng,JiananLi,LijieWang,GuangYang,DunjinChen,XiaoyunShang,JiaChen,XingxuHuang*andJianqiaoLiu*.Highlyefficientandprecisebaseeditingindiscardedhumantripronuclearembryos.ProteinCell,2017,8:776-779 14.BeiYang*,XiaosaLi,LiqunLeiandJiaChen*.APOBEC:frommutatortoeditor.JGenetGenomics,2017,44:423-437 15.JiaChenandAnthonyV.Furano*.Breakingbad:ThemutageniceffectofDNArepair.DNARepair,2015,32:43-51 16.JiaChen,BrendanF.MillerandAnthonyV.Furano*.RepairofnaturallyoccurringmismatchescaninducemutationsinflankingDNA.eLife,2014,3:e02001(HighlightedbySamuelH.Wilson,ThedarksideofDNArepair.eLife,2014,3:e03068) 17.Guang-JingHu#,JiaChen#,Xiao-NanZhao#,Jia-JiaXu,Dong-QingGuo,MingLu,MingZhu,YingXiong,QinLi,CatherineCYChang,Bao-LiangSong,Ta-YuanChangandBo-LiangLi*.ProductionofACAT156-kDaisoforminhumancellsviatrans-splicinginvolvingtheampicillinresistancegene.CellRes,2013,23:1007-1024(Coverstory,HighlightedbyChristianPreußerandAlbrechtBindereif,Exo-endotranssplicing:anewwaytolink.CellRes,2013,23:1071-1072) 18.LeiLei,YingXiong,JiaChen,Jin-BoYang,YiWang,Xin-YingYang,CantherineC.Y.Chang,Bao-LiangSong,Ta-YuanChangandBo-LiangLi*.TNF-alphastimulatestheACAT1expressionindifferentiatingmonocytestopromotetheCE-ladencellformation.JLipidRes,2009,50:1057-1067 19.Xiao-NanZhao#,JiaChen#,LeiLei,Guang-JingHu,YingXiong,Jia-JiaXu,QinLi,Xin-YingYang,CatherineCYChang,Bao-LiangSong,Ta-YuanChangandBo-LiangLi*.Theoptionallong5'-untranslatedregionofhumanACAT1mRNAsimpairstheproductionofACAT1proteinbypromotingitsmRNAdecay.ActaBiochimBiophysSin,2009,41:30-41 20.JiaChen#,Xiao-NanZhao#,LiYang,Guang-JingHu,MingLu,YingXiong,Xin-YingYang,CatherineCYChang,Bao-LiangSong,Ta-YuanChangandBo-LiangLi*.RNAsecondarystructureslocatedintheinterchromosomalregionofhumanACAT1chimericmRNAarerequiredtoproducethe56-kDaisoform.CellRes,2008,18:921-936 21.Bo-LiangLi*,Ta-YuanChang,JiaChen,CatherineCYChangandXiao-NanZhao.HumanACAT1geneexpressionanditsinvolvementinthedevelopmentofatherosclerosis.FutureCardiol,2006,2:93-99 22.LiYang,OneilLee,JiaChen,JiangChen,CatherineC.Y.Chang,PeiZhou,Zhen-ZhenWang,Han-HuiMa,Hui-FangSha,Jiu-XianFeng,YiWang,Xin-YingYang,LiWang,RuhongDong,KimOrnvold,Bo-LiangLi*andTa-YuanChang*.Humanacyl-coenzymeA:cholesterolacyltransferase1(Acat1)sequenceslocatedintwodifferentchromosomes(7and1)arerequiredtoproduceanovelACAT1isoenzymewithadditionalsequenceattheN-terminal.JBiolChem,2004,279:46253-46262 23.LiYang,Jin-BoYang,JiaChen,Guang-YaoYu,PeiZhou,LeiLei,Zhen-ZhenWang,CatherineC.Y.Chang,Xin-YingYang,Ta-YuanChang*andBo-LiangLi*.EnhancementofhumanACAT1geneexpressiontopromotethemacrophage-derivedfoamcellformationbydexamethasone.CellRes,2004,14:315-323(Coverstory)

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