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陈佳    助理教授、研究员
所在学院 生命科学与技术学院
研究方向 DNA修复、基因编辑与癌症发生
联系方式 chenjia@@shanghaitech.edu.cn
备注 优青
 
  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。
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。
目前承担国家自然科学基金委青年项目、面上项目、优青项目,科技部重点研发计划等项目。
  主要研究内容  
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。
  代表性论文  

(#co-first author, * corresponding author)

1.  Jianan Li#, Zhen Liu#, Shisheng Huang#, Xiao Wang, Guanglei Li, Yuting Xu, Wenxia Yu, Shanshan Chen, Yu Zhang, Hanhui Ma, Zunfu Ke, Jia Chen*, Qiang Sun* and Xingxu Huang*. Efficient base editing in G/C-rich regions to model androgen insensitivity syndrome. Cell Res, 2019, doi: 10.1038/s41422-018-0133-4

2.  Xiao Wang#, Jianan Li#, Ying Wang#, Bei Yang#, Jia Wei#, Jing Wu, Ruixuan Wang, Xingxu Huang*, Jia Chen* and Li Yang*. Efficient base editing in methylated regions with a human APOBEC3A-Cas9 fusion. Nat Biotechnol, 2018, 36: 946-949 (Highlighted by Nicole Rusk, Better base editors. Nat Methods, 2018, 15: 763)

3.  Yanting Zeng#, Jianan Li#, Guanglei Li#, Shisheng Huang, Wenxia Yu, Yu Zhang, Dunjin Chen, Jia Chen, Jianqiao Liu* and Xingxu Huang*. Correction of the Marfan Syndrome pathogenic FBN1 mutation by base editing in human cells and heterozygous embryos. Mol Ther, 2018, 26: 2631-2637

4.  Zhen Liu#, Zongyang Lu#, Guang Yang#, Shisheng Huang, Guanglei Li, Songjie Feng, Yajing Liu, Jianan Li, Wenxia Yu, Yu Zhang, Jia Chen, Qiang Sun* and Xingxu Huang*. Efficient generation of mouse models of human diseases via ABE-and BE-mediated base editing. Nat Commun, 2018, 9: 2338

5.  Wen Jiang#, Songjie Feng#, Shisheng Huang, Wenxia Yu, Guanglei Li, Guang Yang, Yajing Liu, Yu Zhang, Lei Zhang, Yu Hou, Jia Chen, Jieping Chen* and Xingxu Huang*. BE-PLUS: a new base editing tool with broadened editing window and enhanced fidelity. Cell Res, 2018, 28: 855-861

6.  Jia Chen, Weizhi Ji and Prashant Mali. The Future of Genome Editing. Cell, 2018, 173: 1311-1313

7.   Xiaosa Li#, Ying Wang#, Yajing Liu#, Bei Yang#, Xiao Wang, Jia Wei, Zongyang Lu, Yuxi Zhang, Jing Wu, Xingxu Huang*, Li Yang* and Jia Chen*. Base editing with a cpf1-cytidine deaminase fusion. Nat Biotechnol, 2018, 36: 324-327 (Highlighted in Tools in Brief, Expanding the range of base editors. Nat Methods, 2018, 15: 314)

8. Liqun Lei#, Hongquan Chen#, Wei Xue#, Bei Yang#, Bian Hu#, Jia Wei, Lijie Wang, Yiqiang Cui, Wei Li, Jianying Wang, Lei Yan, Wanjing Shang, Jimin Gao, Jiahao Sha, Min Zhuang, Xingxu Huang, Bin Shen*, Li Yang* and Jia Chen*. APOBEC3 induces mutations during repair of CRISPR–Cas9-generated DNA breaks. Nat Struct Mol Biol, 2018, 25: 45-52

9.  Lijie Wang#, Wei Xue#, Lei Yan#, Xiaosa Li, Jia Wei, Miaomiao Chen, Jing Wu, Bei Yang*, Li Yang* and Jia Chen*. Enhanced base editing by co-expression of free uracil DNA glycosylase inhibitor. Cell Res, 2017, 27: 1289-1292

10.  Guanglei Li, Yajing Liu, Yanting Zeng, Jianan Li,Lijie Wang, Guang Yang, Dunjin Chen, Xiaoyun Shang, Jia Chen, Xingxu Huang* and Jianqiao Liu*. Highly efficient and precise base editing in discarded human tripronuclear embryos. Protein Cell, 2017, 8: 776-779

11.  Bei Yang*, Xiaosa Li, Liqun Lei and Jia Chen*. APOBEC: from mutator to editor. J Genet Genomics, 2017, 44: 423-437

12.  Jia Chen and Anthony V. Furano*. Breaking bad: The mutagenic effect of DNA repair. DNA Repair, 2015, 32: 43-51

13.  Jia Chen, Brendan F. Miller and Anthony V. Furano*. Repair of naturally occurring mismatches can induce mutations in flanking DNA. eLife, 2014, 3: e02001 (Highlighted by Samuel H. Wilson, The dark side of DNA repair. eLife, 2014, 3: e03068)

14.  Guang-Jing Hu#, Jia Chen#, Xiao-Nan Zhao#, Jia-Jia Xu, Dong-Qing Guo, Ming Lu, Ming Zhu, Ying Xiong, Qin Li, Catherine CY Chang, Bao-Liang Song, Ta-Yuan Chang and Bo-Liang Li*. Production of ACAT1 56-kDa isoform in human cells via trans-splicing involving the ampicillin resistance gene.Cell Res, 2013, 23: 1007-1024 (Cover story, Highlighted by Christian Preußer and Albrecht Bindereif, Exo-endo trans splicing: a new way to link. Cell Res, 2013, 23: 1071-1072)

15.  Lei Lei, Ying Xiong, Jia Chen, Jin-Bo Yang, Yi Wang, Xin-Ying Yang, Cantherine C. Y. Chang, Bao-Liang Song, Ta-Yuan Chang and Bo-Liang Li*. TNF-alpha stimulates the ACAT1 expression in differentiating monocytes to promote the CE-laden cell formation. J Lipid Res, 2009, 50: 1057-1067

16.  Xiao-Nan Zhao#, Jia Chen#, Lei Lei, Guang-Jing Hu, Ying Xiong, Jia-Jia Xu, Qin Li, Xin-Ying Yang, Catherine CY Chang, Bao-Liang Song, Ta-Yuan Chang and Bo-Liang Li*. The optional long 5'-untranslated region of human ACAT1 mRNAs impairs the production of ACAT1 protein by promoting its mRNA decay. Acta Biochim Biophys Sin, 2009, 41: 30-41

17.  Jia Chen#, Xiao-Nan Zhao#, Li Yang, Guang-Jing Hu, Ming Lu, Ying Xiong, Xin-Ying Yang, Catherine CY Chang, Bao-Liang Song, Ta-Yuan Chang and Bo-Liang Li*. RNA secondary structures located in the interchromosomal region of human ACAT1 chimeric mRNA are required to produce the 56-kDa isoform. Cell Res, 2008, 18: 921-936

18.  Bo-Liang Li*, Ta-Yuan Chang, Jia Chen, Catherine CY Chang and Xiao-Nan Zhao. Human ACAT1 gene expression and its involvement in the development of atherosclerosis. Future Cardiol, 2006, 2: 93-99

19.  Li Yang, Oneil Lee, Jia Chen, Jiang Chen, Catherine C.Y. Chang, Pei Zhou, Zhen-Zhen Wang, Han-Hui Ma, Hui-Fang Sha, Jiu-Xian Feng, Yi Wang, Xin-Ying Yang, Li Wang, Ruhong Dong, Kim Ornvold, Bo-Liang Li* and Ta-Yuan Chang*. Human acyl-coenzyme A:cholesterol acyltransferase 1(Acat1) sequences located in two different chromosomes (7 and 1) are required to produce a novel ACAT1 isoenzyme with additional sequence at the N-terminal. J Biol Chem, 2004, 279: 46253-46262

20.  Li Yang, Jin-Bo Yang, Jia Chen, Guang-Yao Yu, Pei Zhou, Lei Lei, Zhen-Zhen Wang, Catherine C.Y. Chang, Xin-Ying Yang, Ta-Yuan Chang* and Bo-Liang Li*. Enhancement of human ACAT1 gene expression to promote the macrophage-derived foam cell formation by dexamethasone. Cell Res, 2004, 14: 315-323 (Cover story)



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