Group leader:
Dr Chen have been pursuing biological research in the area of microbial genomics and synthetic biology for more than 20 years, and published more than 50 peer-reviewed papers in scientific journals including PNAS, JACS, Nucleic Acids Res, Clin Infect Dis (CID) and Angew Chem Int Edit. He received his Ph.D. degree in biochemistry and molecular biology in 2003 from Key Lab for Molecular Enzymology and Engineering of Ministry of Education, College of Life Science, Jilin University. Then he worked there as an Assistant Professor for two years. During that period, he conducted research on developing a novel beta-lactamase inhibitor using DNAzyme (one type of DNA molecule with catalytic activity), and published three papers on the SCI journals as first author (Nucleic Acids Res, 2004; Oligonucleotides, 2004; Chem Res. Chinese U, 2008). Notably, he developed a novel replicating circular DNAzyme against the ampicillin-resistant gene, which displayed inhibitory effects on drug-resistant bacteria (Chinese patent: CN 02109145. 5). In 2005, He joined Dr. Steven Benner (a pioneer in the field of "synthetic biology") group at University of Florida as a Postdoctoral Associate. From 2006 to 2012, he worked as a Research Scientist, then was promoted to a Senior Research Scientist in the “Foundation for Applied Molecular Evolution” (Director: Steven A Benner). He has published more than ten papers on internationally peer reviewed journals as either first author or co-author [PNAS (2010), JACS (2011), Nucleic Acids Res (2011) and Angew Chem Int Edit (Jan 2010, Jul 2010)], and was granted three joint patents (PCT Patent: US2009 004718, 2009; PCT Patent: US2009 003595, 2009; US Patent: 12383776, 2009). During this period, his research mainly focused on development of high-throughput sequencing and molecular diagnostic technology based on synthetic biology. Notably, he combined structural analyses with a "Reconstructed Evolutionary Adaptive Path" (REAP) analysis to substitute the amino acids of DNA polymerase based on its evolutionary and functional history, which enables the modified DNA polymerase to accept a novel high-throughput sequencing reagent (3'-ONH2 reversible terminator). This important finding had been published in PNAS (2010) as the first author, and also he was co-patented (2009) with US Patent number of 12383776. In September 2011, he joined BIG as a Professor under the “100 talents program of CAS”. His current research interests are mainly focused on microbial genomics and metagenomics, especially genomic analysis of respiratory pathogenic bacteria such as M. tuberculosis and K. pneumonia. Since 2012, he has published many peer-reviewed papers in the SCI journals including Clin Infect Dis (CID, 2019), Nucleic Acid Res (2016), RNA Biology (2019), Front Microbiol (2017, 2018), Front Cell Infect Microbiol (2017), Antimicrob Agents Chemother (AAC, 2019), and meanwhile, owned three joint patents (CN201710422881.X; CN201710711058.0; CN201611161033.X).
Introduction:
1. Microbial genomics and metagenomics:
(1) Precision genomic analysis of pathogenic microorganism: according to the World Health Organization’s reports, tuberculosis (TB) and multidrug resistant bacteria-origin pneumonia have been categorized as the two most lethal respiratory infections based on the survey data that TB has exceeded HIV as the most lethal infectious disease globally since 2014 as well as in 2016, ~3 million people died from non-TB respiratory infections mainly caused by drug-resistant pathogens such as Klebsiella pneumonia. Clarification of pathogenic and drug-resistant characteristics of the respiratory pathogens at genetic/epigenetic levels is imperative to eventually control these deadly diseases. Rapid progress on high-throughput sequencing technology provides an opportunity for achieving this goal. Our research interests are mainly focused on microbial genomics, especially genomic analysis of respiratory pathogenic bacteria, such as Mycobacterium tuberculosis (Mtb) and Klebsiella pneumonia (Kpn), through integrating multi-omics data, which is specified as follows. 1) Systematically analyzing the relationship between genotype and phenotype of various respiratory pathogenic bacteria, and exploring the genetic basis/molecular mechanism for their pathogenesis and drug-resistance through associating omics data with clinical phenotypes; 2) Constructing precision methylome of the aforementioned bacteria, and further revealing their epigenetic regulatory mechanism through mining the DNA methylation modification data; 3) Establishing the immune network of the host-cells infected with respiratory pathogenic bacteria using suitable cell or animal models; 4) Discovering novel diagnostic markers and therapeutic targets by integrating the above data in aims to promote the development of precision medicine in human respiratory infectious diseases.
(2) Metagenomics analysis: we focused on the oral and gut microbiota analysis of type II diabetes, Parkinson's disease and respiratory diseases (such as pulmonary tuberculosis, pneumonia and lung cancer). By sequencing large samples of microbiota, we tried to investigate the microbial feature of the diseases (including specific bacterial flora, community structure and metabolism pathway), and further figure out the relationship between the diseases and microbiota. Our ultimate goal is to discover some microbial markers in the diagnosis, prevention and treatment of the aforementioned diseases.
2. Research on DNA (digital) data storage: DNA (digital) data storage is defined as the process of encoding and decoding binary data to and from synthesized DNA strands. It stores the data information in nucleotide sequence (i. e., arrangement and combination of A, T, C, G). As an emerging technology, it breaks through the traditional data storage method using solid media (hard disk, CD, tape, etc). In addition, compared with traditional data storage technology, DNA data storage technology has many advantages such as high data-storage density, long storage time, low energy consumption, easy to carry and transport. We have worked on development of a new DNA data storage technology to achieve the aforementioned goals.
Selected Publication
1. Hairong Huang, Nan Ding, Tingting Yang, Cuidan Li, Xinmiao Jia, Guirong Wang, Jun Zhong, Ju Zhang, Guanglu Jiang, Shuqi Wang, Zhaojing Zong, Wei Jing, Yongliang Zhao, Shaofa Xu*, Fei Chen*. Cross-sectional whole-genome sequencing and epidemiological study of multidrugresistant Mycobacterium tuberculosis in China. Clin Infect Dis (CID), doi:10.1093/cid/ciy883, 2019.
2.Dingxia Shen, Guannan Ma, Cuidan Li, Xinmiao Jia, Chuan Qin, Tingting Yang, Lifeng Wang, Nan Ding, Liya Yue, Zhe Yin, Lijun Zeng, Yongliang Zhao, Dongsheng Zhou*, Fei Chen*. Emergence of a multidrug-resistant hypervirulent Klebsiella pneumoniae of ST23 with a rare blaCTX-M-24-harboring virulence plasmid. Antimicrob Agents Chemother (AAC), 63(3): e02273-18, 2019.
3.Ju Zhang, Xiuli Zhang, Cuidan Li, Liya Yue, Nan Ding, Tim Riordan, Li Yang, Yang Li, Charles Jen, Sen Lin, Dongsheng Zhou, Fei Chen*. Circular RNA profiling provides insights into their subcellular distribution and molecular characteristics in HepG2 cells. RNA Biology, 10.1080/15476286.2019.1565284, 2019.
4.Tingting Yang, Jun Zhong, Ju Zhang, Cuidan Li, Xia Yu, Jingfa Xiao, Xinmiao Jia, Nan Ding, Guannan Ma, Guirong Wang, Liya Yue, Qian Liang, Yongjie Sheng, Yanhong Sun, Hairong Huang* and Fei Chen*. Pan-genomic study of Mycobacterium tuberculosis reflecting the primary/secondary genes, generality/individuality, and the interconversion through copy number variations. Front Microbiol, 9: 1886, 2018.
5.Yongbing Zhao, Chen Sun, Dongyu Zhao, Yadong Zhang, Yang You, Xinmiao Jia, Junhui Yang, Lingping Wang, Jinyue Wang, Haohuan Fu, Yu Kang, Fei Chen, Jun Yu, Jiayan Wu* and Jingfa Xiao*. PGAP-X: extension on pan-genome analysis pipeline. BMC Genomics, 19 (Suppl 1): 36, 2018.
6.Xinmiao Jia, Li Yang, Mengxing Dong, Suting Chen, Lingna Lv, Dandan Cao, Jing Fu, Tingting Yang, Ju Zhang, Xiangli Zhang, Yuanyuan Shang, Guirong Wang, Yongjie Sheng, Hairong Huang* and Fei Chen*. The Bioinformatics Analysis of Comparative Genomics of Mycobacterium tuberculosis Complex (MTBC) Provides Insight into Dissimilarities between Intraspecific Groups Differing in Host Association, Virulence, and Epitope Diversity. Front Cell Infect Microbiol, 7: 88, 2017.
7.Lingna Lv, Cuidan Li, Xiuli Zhang, Nan Ding, Tianshu Cao, Xinmiao Jia, Jinghui Wang, Liping Pan , Hongyan Jia, Zihui Li, Ju Zhang, Fei Chen* and Zongde Zhang*. RNA Profiling Analysis of the Serum Exosomes Derived from Patients with Active and Latent Mycobacterium tuberculosis Infection. Front Microbiol, 8: 1051, 2017.
8.Lei Zhang, Jun Zhong, Hao Liu, Kaiyun Xin, Chaoqiong Chen, Qiqi Li, Yahong Wei, Yao Wang, Fei Chen*, Xihui Shen*. Complete genome sequence of the drought resistance-promoting endophyte Klebsiella sp. LTGPAF-6F. J Biotechnol, 246: 36-39, 2017.
9.Yahong Wei , Jing Fu, Jianying Wu, Xinmiao Jia, Yunheng Zhou, Cuidan Li, Mengxing Dong, Shanshan Wang, Ju Zhang*, Fei Chen*. Bioinformatics analysis and characterization of highly efficient polyvinyl alcohol (PVA)-degrading enzymes from the novel PVA degrader Stenotrophomonas rhizophila QL-P4. Appl Environ Microbiol, 84 (1): e01898-17, 2017.
10.Qing Liu, Guocheng Liu, Ting Wang, Jing Fu, Rujiao Li, Linlin Song, Zhen-Gang Wang*, Baoquan Ding* and Fei Chen*. Enhanced Stability of DNA Nanostructures by Incorporation of Unnatural Base Pairs (UBPs). ChemPhysChem, 18(21): 2977-2980, 2017.
11.Fei Chen*, Yuan Zhang, Ashley B. Daugherty, Zunyi Yang, Ryan Shaw, Mengxing Dong, Steven A. Benner*. Biological phosphorylation of an Unnatural Base Pair (UBP) using a Drosophila melanogaster deoxynucleoside kinase (DmdNK) mutant. PLoS ONE, 12 (3), e0174163, 2017.
12.Mariko F. Matsuura, Christian B. Winiger, Ryan W. Shaw, Myong-Jung Kim, Myong-Sang Kim, Ashley B. Daugherty, Fei Chen, Patricia Moussatche, Jennifer D. Moses, Stefan Lutz, and Steven A. Benner*. A Single Deoxynucleoside Kinase Variant from Drosophila melanogaster Synthesizes Monophosphates of Nucleosides That Are Components of an Expanded Genetic System. ACS Synth Biol, 6 (3): 388 - 394, 2017.
13.Jun Yang, Yan Liu, Bing Wang, Hongzhen Lan, Ying Liu, Fei Chen, Ju Zhang and Jian Luo*. Sumoylation in p27kip1 via RanBP2 promotes cancer cell growth in cholangiocarcinoma cell line QBC939. BMC Mol Biol, 18: 23, 2017.
14.Lingxiang Zhu, Jun Zhong, Xinmiao Jia, Guan Liu, Yu Kang, Mengxing Dong, Xiuli Zhang, Qian Li, Liya Yue, Cuidan Li, Jing Fu, Jingfa Xiao, Jiangwei Yan, Bing Zhang, Meng Lei, Suting Chen, Lingna Lv, Baoli Zhu, Hairong Huang* and Fei Chen*. Precision methylome characterization of Mycobacterium tuberculosis complex (MTBC) using PacBio Single-Molecule Real-Time (SMRT) Technology. Nucleic Acids Res, 44(2): 730-743, 2016.
15.Xinpeng Tian, Zhewen Zhang, Tingting Yang, Meili Chen, Jie Li, Fei Chen, Jin Yang, Wenjie Li, Bing Zhang, Zhang Zhang, Jiayan Wu, Changsheng Zhang, Lijuan Long* and Jingfa Xiao*. Comparative Genomics Analysis of Streptomyces Species Reveals Their Adaptation to the Marine Environment and Their Diversity at the Genomic Level. Front Microbiol, 7: 998, 2016.
16.Zhang Z*, Hu S*, He H*, Zhang H*, Zhang Z, Hu S, He H, Chen F, Zhao W, Xiao J, Chen LL, Xue Y, Wang X, Xia L, Wang X, Luo Y, Wu S, Hao L, Zou D, Yang L, Huang D, Xu X, Yan W, Li Q, Zhong J, Hao L, Zou D, Xu X, Huang D, Xu X, Yuan F, Zhang Y, Sang J, Ma L, Liu S, Zou D, Cheng H, Wang Y, Deng W, Zhang Z, Hu S, He H, Chen F, Chen LL, Xue Y, Ji Z. IC4R Project Consortium, Information Commons for Rice (IC4R). Nucleic Acids Res, 44 (D1): D1172-80, 2016.
17.Yu Kang, Chaohao Gu, Lina Yuan, Yue Wang, Yanmin Zhu, Xinna Li, Qibin Luo, Jingfa Xiao, Daquan Jiang, Minping Qian, Aftab Ahmed Khan, Fei Chen, Zhang Zhang*, Jun Yu*. Flexibility and symmetry of prokaryotic genome rearrangement reveal lineage-associated core-gene-defined genome organizational frameworks. mBio, 5(6): e01867-14, 2015.
18.Yiyangzi Ma, Na Shi, Mengtao Li, Fei Chen, Haitao Niu*. Applications of Next-generation Sequencing in Systemic Autoimmune Diseases. Genomics Proteomics Bioinformatics, 13(4):242-9, 2015.
19.Dai L, Xu C, Tian M, Sang J, Zou D, Li A, Liu G, Chen F, Wu J, Xiao J, Wang X, Yu J, Zhang Z. Community intelligence in knowledge curation: an application to managing scientific nomenclature. PLoS ONE. 8(2): e56961, 2013.
20.Yang Z, Durante M, Glushakova LG, Sharma N, Leal NA, Bradley KM, Chen F, Benner SA. Conversion strategy using an expanded genetic alphabet to assay nucleic acids. Anal Chem. 85 (9): 4705-12, 2013.
21.Fei Chen*, Mengxing Dong, Meng Ge, Lingxiang Zhu, Lufeng Ren, Guocheng Liu, and Rong Mu. The history and advances of reversible terminators used in new generations of sequencing technology. Genomics Proteomics Bioinformatics, 11(1):34-40, 2013.
22.Yang, ZY#., Chen, F.#, Brian, JA., Benner, SA. Amplification, Mutation, and Sequencing of a Six-Letter Synthetic Genetic System. (2011) J Am Chem Soc. 133(38), 15105-12. (#Co-First Author).
23.Chen, F., Yang ZY, Yan MC, Brian JA, Wang GG, Benner SA. Recognition of an expanded genetic alphabet by type-II restriction endonucleases and their application to analyze polymerase fidelity. (2011) Nucleic Acid Res. 39 (9), 3949-61.
24.Chen, F., Gaucher, E. A., Leal, N. A., Hutter, D., Havemann, S. A., Govindarajan, S., Ortlund, E. A., Benner, S. A. (2010) Reconstructed evolutionary adaptive paths give polymerases accepting reversible terminators for sequencing and SNP detection. Proc. Natl. Acad. Sci. USA. 107, 1948-1953.
25.Yang, Z., Chen, F., Chamberlin, S. G., Benner, S. A. (2010) Expanded genetic alphabets in the polymerase chain reaction. Angew. Chem. Int. Edit, 49, 177-180. (“Faculty of 1000 Biology” Selection).
26.Hoshika, S., Chen, F., Leal, N., Benner, S.A. (2010) Artificial genetic systems. Self-avoiding DNA in PCR and multiplexed PCR. Angew. Chem. Int. Edit, 49, 5554-5557 (“Hot paper” Selection).
27.Benner, S. A., Chen, F., Yang, Z. Y. (2011) Synthetic Biology, Tinkering Biology, and Artificial Biology: A Perspective from Chemistry. pp. 69-106. In Luisi, P. L., ed. Chemical Synthetic Biology, Cambridge University pp. 69 - 106.
28.Chen, F., Li, Z., Yang, S., Wang, RJ., Liu, B., Song, YM., Sun, YH., Hao, DY. and Wang, XP. Inhibition of Ampicillin-resistance in bacteria by modified DNAzymes. (2008) Chem Res. Chinese U. 24(4), 491-5.
29.Chen, F., Wang, R., Li, Z, Liu, B., Wang, XP., Sun, YH., Hao, DY., and Zhang, J. A novel replicating circular DNAzyme. (2004) Nucleic Acid Res, 32(8), 2336-2341.
30.Chen, F., Li, Z., Wang, R.J., Liu, B., Zeng, Z., Zhang, H.Y., Zhang, J. Inhibition of Ampicillin-resistant bacteria by novel mono- and di-DNAzymes targeted to β-lactamase mRNA. (2004) Oligonucleotides, 14(2), 80-89.
Group members:
Staff:
Nan Ding: Assistant Professor
Xiuli Zhang: Assistant Professor
Guannan Ma: Research Assistant
Liya Yue: Research Assistant
Graduate students:
PhD graduates:
Xinmiao Jia (2017), Jing Fu (2018);
Master graduates:
Ya Liu (2015), Hua Xue (2015), Liya Yue (2016), Qian Li (2016), Xiangli Zhang (2018), Shanshan Wang (2018)
PhD students:
Xiuli Zhang, Mengxing Dong, Cuidan Li, Tingting Yang, Li Yang, Gengchao Wang, Shuangshuang Li
Master students:
Chuan Qin, Dandan Lu, Jie Liu, Yicheng Shen, Yijia Tang, Chenyang Wang, Fengyang Cao, Jie Wang, Xue Yang
Contact:
Tel: +86-10-84097460, Fax: +86-10-84097720
