个人简介

Education: B.Sc., University of Science and Technology of China (USTC); Ph.D., University of Rochester; Post-doc: University of California, Berkeley, The Scripps Research Institute

研究领域

Biophysical Chemistry/Single-Molecule Detection and Nanomanipulation/RNA Structures/Properties/and Functions/Therapeutics Targeting RNA and RNA-protein complex.

Research Interest The functions of RNA include coding (for protein, RNA, and DNA), gene regulation, catalysis, and immunomodulation. The overall goal of Gang CHEN research group is to better understand the structures and the physical-chemical properties of RNAs and RNA-ligand complexes to provide deeper insight into and to facilitate precise control of the diverse biological functions involving RNA. The research projects of current interests are: (1) characterizing the molecular recognition interactions (e.g., hydrogen bonding and aromatic base stacking) accounting for structure, stability, and dynamics of RNA structural building blocks such as internal loops, hairpins, triplexes, and pseudoknots, (2) probing the complex energy landscapes of RNA folding and assembly with protein, and (3) designing and discovering therapeutic ligands (small molecules, oligonucleotides, peptides, and peptide nucleic acids) targeting RNA and RNA-protein complex. We employ various conventional and cutting-edge biophysical, biochemical, and bioorganic techniques including single-molecule nano-manipulation using laser optical tweezers, NMR, UV-Vis, AFM, bulk and single-molecule fluorescence, SPR, ITC, chemical synthesis of modified oligonucleotides and peptides, PCR, gel electrophoresis, in vitro transcription and translation, and protein expression and purification. The research experience in the laboratory will help the students to grasp fundamental knowledge and experimental skills, to develop learning skills such as rigorous reasoning and innovative thinking, and to be able to ask and answer important questions within and beyond chemical and molecular sciences. Many viruses including HIV-1, SARS-CoV, and some agriculturally important plant viruses have evolved programmed ribosomal frameshift to express defined ratios of structural and enzymatic proteins. Highly efficient frameshift at an mRNA slippery sequence from X XXY YYZ (0 frame) to XXX YYY Z (–1 frame) is often stimulated by a down-stream mRNA structure, e.g., pstudoknot. Innate immune response is the first line of defense of host cells in mammals against virus infection. The discoveries concerning the activation of innate immunity were awarded the Nobel Prize in Physiology or Medicine in 2011. One major type of innate immune receptors, Toll-like receptors, have been the targets of nucleic acid vaccine adjuvants in clinical trials. RIG-I is a newly discovered cytosolic pattern-recognition receptor that senses viral RNAs released from replicating viruses in infected cells. (Left) Crystal structure (PDB: 3NCU) of the RIG-I C-terminal domain (CTD) (shown in blue) in complex with a 12-bp dsRNA with 5′-pp. RIG-I CTDs are bound to both ends of the dsRNA. (Right) Crystal structure (PDB: 2YKG) of the two-domain RIG-I helicase-CTD in complex with a 10-bp dsRNA with 5′-OH. RIG-I CTD is bound to one terminal end of the dsRNA, with the helicase domain wrapping around the dsRNA.

近期论文

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Gitali Devi,= Yuan Zhou,= Zhensheng Zhong,= Desiree-Faye Kaixin Toh,= and Gang Chen,* (2015) RNA Triplexes – From Structural Principles to Biological and Biotech Applications. Wiley Interdiscip Rev RNA, 6, 111-28 Xing Ma,= Gitali Devi,= Qiuyu Qu, Desiree-Faye Kaixin Toh, Gang Chen,* Yanli Zhao,* (2014) Intracellular Delivery of Antisense Peptide Nucleic Acid by Fluorescent Mesoporous Silica Nanoparticles, Bioconjugate Chem, 25, 1412-20 Gitali Devi, Zhen Yuan, Yunpeng Lu, Yanli Zhao,* and Gang Chen,* (2014) Incorporation of thio-pseudoisocytosine into triplex-forming peptide nucleic acids for enhanced recognition of RNA duplexes. Nucleic Acids Res, 42, 4008-18. Yuan Zhou, Elzbieta Kierzek, Zi Ping Loo, Meraldo Antonio, Yin Hoe Yau, York Wieo Chuah, Susana Geifman-Shochat, Ryszard Kierzek,* and Gang Chen,* (2013) Recognition of RNA duplexes by chemically modified triplex-forming oligonucleotides. Nucleic Acids Res 41, 6664-73. Chen, G., Chang, K.-Y., Chou, M.-Y., Bustamante, C., and Tinoco, I., Jr.* (Aug 2009) Triplex structures in an RNA pseudoknot enhance mechanical stability and increase efficiency of –1 ribosomal frameshifting. Proc. Natl. Acad. Sci. USA 106(31), 12706-11 Chen, G., Kennedy, S.D., and Turner, D.H.* (Jun 2009) A CA+ pair adjacent to a sheared GA or AA pair stabilizes size-symmetric RNA internal loops. Biochemistry 48(24), 5738-52. Chen, G., Wen, J.-D., and Tinoco, I., Jr.* (Dec 2007) Single-molecule mechanical unfolding and folding of a pseudoknot in human telomerase RNA. RNA 13(12), 2175-88 Chen, G., Kierzek, R., Yildirim, I., Krugh, T.R., Turner, D.H.,* and Kennedy, S.D. (Jun 2007) Stacking effects on local structure in RNA: Changes in the structure of tandem GA pairs when flanking GC pairs are replaced by isoG-isoC pairs. J. Phys. Chem. B 111(24), 6718-27 Shankar, N., Kennedy, S.D., Chen, G., Krugh, T.R., and Turner, D.H.* (Oct 2006) The NMR structure of an internal loop from 23S ribosomal RNA differs from its structure in crystals of 50S ribosomal subunits. Biochemistry 45(39), 11776-89 Chen, G., Kennedy, S.D., Qiao, J., Krugh, T.R., and Turner, D.H.* (Jun 2006) An alternating sheared AA pair and elements of stability for a single sheared purine-purine pair flanked by sheared GA pairs in RNA. Biochemistry 45(22), 6889-903 Chen, G., and Turner, D.H.* (Mar 2006) Consecutive GA pairs stabilize medium-size RNA internal loops. Biochemistry 45(12), 4025-43 Chen, G., Znosko, B.M., Kennedy, S.D., Krugh, T.R., and Turner, D.H.* (Mar 2005) Solution structure of an RNA internal loop with three consecutive GA pairs. Biochemistry 44(8), 2845-56 Chen, G., Znosko, B.M., Jiao, X., and Turner, D.H.* (Oct 2004) Factors affecting thermodynamic stabilities of RNA 3 × 3 internal loops. Biochemistry 43(40), 12865-76 Cui, Y.,* Chen, G., Ren, J., Shao, M., Xie, Y., and Qian, Y.* (Apr 2003) Solvothermal syntheses of β-Ag2Se crystals with novel morphologies. J. Solid State Chem. 172(1), 17-21 Cui, Y.,* Chen, J., Chen, G., Ren, J., Yu, W., and Qian, Y. (Apr 2001) Bis(2,2-bipyridine-N,N')tetra-µ-chloro-tetracopper(I). Acta Crystallogr. Sect. C-Cryst. Struct. Commun. 57, 349-51 Shao, M., Mo, M., Cui, Y., Chen, G., and Qian, Y.* (Dec 2001) The effect of agitation states on hydrothermal synthesis of Bi2S3 nanorods. J. Cryst. Growth 233(4), 799-802 Cui, Y.,* Ren, J., Chen, G., Qian, Y.,* and Xie, Y. (Mar 2001) A simple route to synthesize MInS2 (M = Cu, Ag) nanorods from single-molecule precursors. Chem. Lett., (3) 236-7 Cui, Y.,* Ren, J., Chen, G., Yu, W., and Qian, Y. (Dec 2000) Poly[lead(II)-µ-4,4-bipyridine-N,N'-di-m-bromo]. Acta Crystallogr. Sect. C-Cryst. Struct. Commun. 56, E552-3 Cui, Y., Chen, G., Ren, J., Qian, Y.,* and Huang, J.* (Sep 2000) Syntheses, structures and magnetic behaviors of di- and trinuclear pivalate complexes containing both cobalt(II) and lanthanide(III) ions. Inorg. Chem. 39(18), 4165-8 Cui, Y.,* Zhang, X., Zheng, F., Ren, J., Chen, G., Qian, Y., and Huang, J. (Oct 2000) Two mixed-metal carboxylate-base adducts. Acta Crystallogr. Sect. C-Cryst. Struct. Commun. 56, 1198-200