Jia Chen    Associate Professor, PI
InstituteSchool of Life Science and Technology
Research AreaDNA repair, gene editing and carcinogenesis
Contact Info.chenjia@@shanghaitech.edu.cn

Dr. Jia Chen obtained his bachelor's degree at Department of Biochemistry and Molecular Biology, Nankai University in 2002 and then obtained his Ph. D. at Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences in 2009. From 2009-2014, Dr. Chen received his postdoctoral training in National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health. Since November 2014, Dr. Chen joined ShanghaiTech University as a Tenure-track Assistant Professor, PI in School of Life Sciences and Technology. He was promoted to Tenured Associate Professor in October 2019. Dr. Chen was selected to the “Pujiang Talents Program” organized by Shanghai Science and Technology Commission in 2016.

Research Interests
Species survival is closely related to genome stability, which is monitored and maintained by DNA repair pathways. However, cell can initiate error-prone DNA repair in various physiological and pathological conditions. Thus, the fidelity of DNA repair affects aging, evolution and certain diseases.

Genome editing is a type of genetic engineering in which DNA is inserted, deleted or replaced in the genome of a living organism using engineered nucleases. Utilizing genome editing tools to genetically manipulate the genome of cells and living organism has broad application interest in life sciences research, biotechnology/agricultural technology development and most importantly pharmaceutical/clinical innovation. Though CRISPR/Cas gene editing system is efficient in gene knockout, the efficiency of CRISPR/Cas-mediated base substitution is usually low. Recently, a novel gene editing system, base editing, which combines nucleotide deaminase with the CRISPR/Cas system, has been developed to induce targeted base substitution efficiently.

Our group has revealed the mechanism of APOBEC cytidine deaminase-mediated mutagenesis during the repair of CRISPR/Cas9-generated DNA breaks and developed various base editors for different purposes, including enhanced base editors (eBEs) with improved editing precision and efficiency, dCpf1 base editors (dCpf1-BEs) for base editing in A/T-rich regions and hAPOBEC3A base editors (hA3A-BEs) for efficient base editing in G/C rich and/or highly-methylated regions.

Our group will focus on DNA repair-induced mutagenesis, which underlines the precision of gene editing, the development of certain cancers and aging. We are particularly interested in: 1) Mechanism of DNA repair-induced mutagenesis in gene editing; 2) Development of novel gene editing tools; 3) New proteins and pathways involved in DNA repair-induced mutagenesis; 4) Role of DNA repair-induced mutagenesis in carcinogenesis.

Selected Publications

(# co-first author, * corresponding author)

1.Jia Chen*, Bei Yang* and Li Yang*. To BE or not to BE, that is the question. Nat Biotechnol, 2019, doi: 10.1038/s41587-019-0119-x

2.Bei Yang*, Li Yang* and Jia Chen*. Development and Application of Base Editors. CRISPR J, 2019, 2: 91-104

3.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, 29: 174-176

4.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)

5.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

6.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

7.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

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

9.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)

10.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

11.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

12.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

13.Bei Yang*Xiaosa Li, Liqun Lei and Jia Chen*. APOBEC: from mutator to editor. J Genet Genomics2017, 44: 423-437

14.Jia Chenand Anthony V. Furano*. Breaking bad: The mutagenic effect of DNA repair. DNA Repair2015, 32: 43-51

15.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)

16.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 storyHighlighted by Christian Preußer and Albrecht Bindereif, Exo-endo trans splicing: a new way to link. Cell Res, 2013, 23: 1071-1072)

17.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

18.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

19.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

20.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

21.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

22.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)