071010 Biochemistry and molecular biology

0710J3 Bioinformatics

0710Z1 Genomics

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Molecular Genetics and Epigenetics

Omics in Diseases

Dr. CHEN Fei is currently a professor in “100 talents program” of Chinese Academy of Sciences (CAS). He received his Ph.D. degree in biochemistry and molecular biology in 2003 from Jilin University. In 2005, he entered the University of Florida as a postdoctoral associate in the group of Dr Steven Benner. From 2006 to 2012, he worked as a research scientist, then a senior research scientist in the Foundation for Applied Molecular Evolution, Inc. His research interest is mainly focused on the structural and functional genomics of pathogens, as well as metagenomics. He has published number of peer-reviewed papers in scientific journals including “PNAS”, “JACS”, and “Nucleic Acid Res”, and also jointly owned three patents.

Dr. Chen’s research mainly focuses on precision genomics, including precision genome and epigenome characterization of pathogenic microorganisms (such as Mycobacterium tuberculosis, Klebsiella Pneumoniae, Pseudomonas aeruginosa and other important pathogens), metagenomics and cancer genomics. Besides, based on quick and accurate technology to detect nucleic acid in clinical samples, we are developing differential diagnosis kit for HIV drug-resistant genotype and various respiratory pathogens. Specific research fields are as followings: 

1，Precision genomics research of major diseases: Precision genomics research of pathogenic microorganisms (Mycobacterium tuberculosis, Klebsiella pneumoniae, etc), metagenomic study of intestinal microbiota in type II diabetes and non-coding RNA research concerned with cancer and other major diseases are all included. Our group panoramically studies genome structure, variation, function and evolution of the aforementioned diseases through the integration of multi-omics analysis with large samples of patients. We also discover disease-related functional elements or target sites and further reveal the molecular mechanisms of these diseases, providing a basis for accurate diagnosis and treatment of disease. 

1) Precision genomics research of pathogenic microorganisms: Our research group, cooperating with the General Hospital of the People's Liberation Army (PLAGH), Peking University People's Hospital, Beijing Tuberculosis and Thoracic Tumor Research Institute and other hospitals, selects Mycobacterium tuberculosis, Klebsiella Pneumoniae, Pseudomonas aeruginosa and other important pathogens for study. Through integrating multiple sets of data of genomics, transcriptomics, proteomics and metabolomics, we study systematically on the life history of these pathogenic strains and pathogenesis to reveal the molecular regulation mechanisms of pathogenicity, antigenicity, drug resistance and persistence of these pathogens during infecting and residing, providing technical support for accurate diagnosis and treatment of infectious diseases. 

2）Metagenomic study of intestinal microbiota in type II diabetes: Our group is now cooperating with Xiyuan hospital (CACMS) and other hospitals on this project. We select patients with type II diabetes in different courses as research object. By sequencing large samples of intestinal microbiota, we fully analyze intestinal microbial features of type II diabetes patients, including specific bacterial flora, community structure and metabolism pathway, to create a metagenomic database of Chinese type II diabetes crowd. Base on this, this project is designed to further reveal the mechanism of the interaction between genetic factors and intestinal microbiota of type II diabetes patients in depth, and identify molecular targets that can be used to treat type II diabetes, which might provide guidance for prevention and early detection of type II diabetes. 

3）Related non-coding RNA research on major diseases like cancer: A non-coding RNA (ncRNA) is an RNA molecule which is not translated into a protein. They widely exist in different organisms. In recent years, growing research suggests that ncRNAs previously known as "junk" actually play a very important role in many life processes. Generalized non-coding RNA can be divided into rRNA, tRNA, snRNA, snoRNA, siRNA, miRNA, piRNA, ecRNA, etc. With the in-depth study, a variety of novel ncRNAs are continuously being discovered with various features. Evidence is accumulating that there exists a parallel RNA regulatory network in the living organisms. Although ncRNA has been a hotspot in the biological field, the majority of its research is still in the early stage. Thus, our group select tumor as our research object, investigating the role of two recently discovered ncRNA, circular RNA and exRNA (Extracellular RNA), in tumorigenesis, tumor progression and metastasis and exploring their regulatory mechanism. We expect to get some forward-looking synthesis results supposed to be more comprehensive and more accurate at the genomic level, and finally pinpoint precision cancer medicine. 

4）Research on cancer epigenome: Epigenomics is an emerging discipline in recent years. It is based on second generation high-throughput sequencing technology, along with base conversion, chemical concentration or antibody capture, to detect modified nucleotides, their distribution over a whole genome and the genetic function. Epigenomics is the interdisipline and development of genomics and epigenetics. It reveals a new regulatory network that lay behind life phenomena. The early period of epigenomics almost focus on DNA 5-methyl pyrimidine (5mC, also named fifth alkali base). With the development of modified nucleic acid sequencing technology, we have successfully achieved whole genome sequencing of variety new modified nucleic acid. Related research results showed that these new modifications existing in DNA or RNA, such as 5-hydroxymethylcytosine (5hmC, also named sixth alkali base), 5-formylcytosine (5fC), 5-carboxylcytosine (5caC) and N6-methyladenosine (m6A), are playing an extremely important role in gene expression, genome variation, cell differentiation and other life processes. Nevertheless, epigenomics is still at the starting stage and there exists expanses of virgin land in this field. Over 130 RNA base modifications, for instance, have been reported; however, most of the related research is only confined in m6A (has not achieved single modified base sequencing yet). In addition, there are very few reports concerning the relationship between modified nucleic acid and DNA/RNA advanced structure. Aiming at the above scientific problems, we find tumor as research object to identify new types of modified nucleotide and their functions with high throughput sequencing technology and nucleic acid chemistry methods. We also develop new sequencing technology that applies to different modified nucleic acid across the whole genome and further reveal the effect of modified nucleic acid regulatory network on life phenomena.                              

2，Accurate detection technology of nucleic acid and development of diagnosis kit: Nucleic acid detection has many advantages such as fast, accurate and requiring less sample volume in comparison with traditional detection methods. Our group uses SAMRS (self-avoiding molecular-recognition system) and AEGIS (artificially expanded genetic information system) which have been both proved excellent in multiplex PCR, and the detection means of three-level gene amplification in order to detect various target pathogenic genes by multiplex PCR at the same time. The three-level detection can satisfy the requirement for sensitively and accurately detecting the amplification products of multiplex PCR, and can be gradually expanded according to demand in order to serve for clinical applications. In particular, introducing AEGIS into nested-PCR primers can not only make the complex multiplex PCR possible, but also greatly improve the sensitivity and specificity of gene amplification, avoiding off-target effects. Our group is currently focusing on the following projects: detection and analysis system for HIV drug resistant genotype (cooperating with National Institutes For Food And Drug Control), test kit for various respiratory pathogens and drug resistance genes detection (cooperating with Peking University People's Hospital and Beijing Tuberculosis and Thoracic Tumor Research Institute), molecular diagnosis kit of early screening for cancer and monitoring postoperative recurrence (cooperating with Repconex Company).

Selected papers

1. Zhu L^#, Zhong J^#, Jia X^#, Liu G^#, Kang Y^#, Dong M, Zhang X, Li Q, Yue L, Li C, Fu J, Xiao J, Yan J, Zhang B, Lei M, Chen S, Lv L, Zhu B, Huang H*, Chen F*. Precision methylome characterization of Mycobacterium tuberculosis complex (MTBC) using PacBio Single-Molecule Real-Time (SMRT) Technology. Nucleic Acids Research. 2016. 44(2): 730-743.(*Co-corresponding author)

2. Chen F, Yang Z, Yan M, Brian JA, Wang GG, Benner SA. Recognition of an expanded genetic alphabet by type-II restriction endonucleases and their application to analyze polymerase fidelity. Nucleic Acid Res. 2011. 39: 3949-61.

3. Yang Z^#, Chen F^#, Brian JA, Benner SA. Amplification, Mutation, and Sequencing of a Six-Letter Synthetic Genetic System. J Am Chem Soc. 2011. 133: 15105-12. (^#Co-First Author).

4. Chen F, Gaucher EA, Leal, NA, Hutter D, Havemann SA, Govindarajan S, Ortlund EA, Benner SA. Reconstructed evolutionary adaptive paths give polymerases accepting reversible terminators for sequencing and SNP detection. Proc. Natl. Acad. Sci. USA. 2010. 107: 1948-53.

5. Yang Z, Chen F, Chamberlin SG, Benner SA. Expanded genetic alphabets in the polymerase chain reaction. Angew. Chem. Int. Edit 2010. 49: 177-80. (“Faculty of 1000 Biology” selection). 

Patents

1. Steven A Benner, Daniel Hutter, Nicole A Leal, Fei Chen. Reagents for reversibly terminating primer extension. US Patent: 20110275124 (2011.11.10).

2. Steven A Benner, Shuichi Hoshika, Fei Chen. Self-avoiding molecular recognition systems in DNA amplification. PCT/US Patent: WO/2010/021702 (2010.02.25).

3. Steven A Benner, Fei Chen, Zunyi Yang. Polymerase Incorporation of Non-Standard Nucleotides. PCT/US Patent: WO/2009/154733 (2009.12.23).

Academic Monographs

Synthetic Biology, Tinkering Biology, and Artificial Biology: A Perspective from Chemistry. pp. 69-106. In Luisi, P. L., ed.，Cambridge University，2011-05，(the Second author)

Staff

Dr. Zhang Ju, Assistant Professor, zhangju@big.ac.cn

Dr. Zhong Jun, Assistant Professor, zhangju@big.ac.cn

Dr. Cao Dandan, Assistant Professor, caodd@big.ac.cn

Dr. Ding Nan, Assistant Professor, dingn@big.ac.cn

Ms. Ma Guannan, magn@big.ac.cn

Ms. Yue Liya, yuely@big.ac.cn

Students

Graduate Students：

FU Jing, 2013, PhD candidate, fujing@big.ac.cn

JIA Xinmiao, 2014, PhD candidate,jiaxm@big.ac.cn

YANG Tingting, 2015, doctor candidate, yangtt@big.ac.cn

YANG Li, 2015, PhD candidate, liyang@big.ac.cn

LI Cuidan, 2014, PhD candidate,licuidan@big.ac.cn

DONG Mengxing, 2014, PhD candidate,dongmx@big.ac.cn

ZHANG Xiangli, 2015, Masteral candidate, zhangxiangli@big.ac.cn

WANG Shanshan, 2015, Masteral candidate, wangshanshan@big.ac.cn

LU Dandan,2016, Masteral candidate, ludandan@big.ac.cn

LIU Jie,2016, Masteral candidate, 156961115@qq.com

Postdoctoral Fellows：

CAO Tianshu,2014