陈刚
副教授
博士 (美国罗切斯特大学化学系)
硕士 (美国罗切斯特大学化学系)
学士 (中国科学技术大学化学系)
陈刚教授于2001年本科毕业于中国科技大学化学系,后赴美国罗切斯特大学(Univ. of Rochester)化学系(2001-2005)攻读生物物理化学博士学位,先后于美国加州大学伯克利分校化学系(UC Berkeley, 2006-2009)和美国斯克利普斯研究所加州校区(Scripps Research, 2009-2010)从事博士后研究。他于2010年加入新加坡南洋理工大学(NTU, Singapore)数理科学院化学与生物化学系并担任助理教授。2020年他加入香港中文大学(深圳),目前担任医学院副教授。
研究团队一直致力于1. 利用生物物理/生物化学方法(包括高分辨率光镊操纵单分子)来表征分子识别作用力如何调控RNA和RNA-配体复合物的结构、稳定性、动力学和生物功能;2. 发展靶向RNA二级结构的可编程修饰肽核酸(PNA)和其它功能分子作为化学生物学研究工具和疾病诊断治疗方法。在靶向识别RNA双螺旋结构的高影响力研究已经引起了RNA学术界的极大兴趣。并撰写了一篇关于RNA三链体的特邀综述文章(Wiley Interdisciplinary Reviews: RNA,2015, 6,111-128);发表了关于碱基三联体对于RNA三维结构和催化活性的重要性的新闻和观点文章(Nature Chemical Biology,2015,11,830-831);贡献了一个特邀书籍章节(2016, Springer出版)综述关于通过双链和三链结构形成来分别识别和靶向成熟miRNA和miRNA发夹前体;受Biochemistry总编辑(Alanna Schepartz)邀请,为 Future of Biochemistry 专刊撰文(Biochemistry, 2018, 57, 149-159)。我们将会不断吸引人才和加强合作以进一步提高研究团队在RNA折叠和分子识别领域的核心竞争力,进一步发展现代生物化学技术、疾病诊断和精准药物设计方法。
Book Chapter
1. Patil, K.M., and Chen, G.* (2016) Recognition of RNA sequence and structure by duplex and triplex formation: targeting miRNA and pre-miRNA, in Modified Nucleic Acids in Biology and Medicine, (Volker A. Erdmann, Stefan Jurga and Jan Barciszewski, Eds.), Springer series: RNA Technologies. Doi: 10.1007/978-3-319-34175-0_13
Patents Filed
1. Singapore Provisional patent: 10201906239R. Title: Compositions and Methods For Inhibition of RNA Editing For Treatment of Cancer.
Inventors: 1) Leilei CHEN; 2) Daryl Jin Tai TAY; 3) Gang CHEN
Applicants: 1) National University of Singapore; 2) Nanyang Technological University
2. PAT/179/14/15/PCT, Title: Modified Peptide Nucleic Acids And Their Use.
Inventors: 1) Gitali DEVI; 2) Desiree-Faye TOH Kaixin; 3) Kiran M. PATIL; 4) QU Qiuyu; 5) Manikantha MARASWAMI; 6) Elzbieta KIERZEK; 7) XIAO Yunyun; 8) LOH Teck Peng; 9) ZHAO Yanli; 10) CHEN Gang.
Applicants: 1) Nanyang Technological University; 2) Institute of Bioorganic Chemistry Polish Academy of Sciences. Singapore PCT Application No: PCT/SG2015/050319. International Filing Date: 15 September 2015.
Journal papers:
1. Maity, A., Winnerdy, F.R., Chang, W.D., Chen, G., and Phan, A.T.* (2020) Intra-locked G-quadruplex structures formed by irregular DNA G-rich motifs. Nucleic Acids Res. 48, 3315–3327. (IF: 11.561)
2. Ong, A.A.L.#, Tan, J.#, Bhadra, M., Dezanet, C., Patil, K.M., Chong, M.S., Kierzek, R., Decout, J.-L., Roca, X., and Chen, G.* (2019) RNA secondary structure-based design of antisense peptide nucleic acids for modulating disease-associated aberrant tau pre-mRNA alternative splicing. Molecules, 24, 3020. (IF: 3.098)
3. Krishna, M.S., Wang, Z., Bowry, J., Wang, Z., Zheng, L., Bowry, J., Ong, A.A.L., Mu, Y., Prabakaran, M., and Chen, G.* (2019) Incorporating G-C Pair-Recognizing Guanidinium into PNAs for Sequence and Structure Specific Recognition of dsRNAs over dsDNAs and ssRNAs. Biochemistry, 58, 3777-3788. (IF: 2.997)
4. Ong, A.A.L.#, Toh, D.-F.K.#, Krishna, M.S., Patil, K.M., Okamura, K., and Chen, G.* (2019) Incorporating 2-thiouracil into short dsRNA-binding PNAs for enhanced recognition of A-U pairs and for targeting a microRNA hairpin precursor. Biochemistry, 58, 3444-3453. (IF: 2.997)
5. Krishna, M.S., Toh, D.-F.K., Meng, Z., Ong, A.A.L., Wang, Z., Lu, Y., Xia, K., Prabakaran, M., and Chen, G.* (2019) Sequence- and structure-specific probing of RNAs by short nucleobase-modified dsRNA-binding PNAs incorporating a fluorescent light-up uracil analog. Anal. Chem., 91, 5331-5338. (IF: 6.042)
6. Tan, J.#, Yang, L.#, Ong, A.A.L., Shi, J., Zhong, Z., Lye, M.L., Liu, S., Lisowiec-Wachnicka, J., Kierzek, R., Roca, X.,* Chen, G.* (2019) A disease-causing intronic point mutation C19G alters tau exon 10 splicing via RNA secondary structure rearrangement. Biochemistry, 58, 1565-1578. (IF: 2.997)
7. Kesy, J.#, Patil, K.M.#, Kumar, S.M.#, Shu, Z., Yee, Y.H., Zimmermann, L., Ong, A.A.L., Toh, D.-F.K., Krishna, M.S., Yang, L., Decout, J.-L., Luo, D., Prabakaran, M.,* Chen, G.,* and Kierzek, E.* (2019) A short chemically modified dsRNA-binding PNA (dbPNA) inhibits influenza viral replication by targeting viral RNA panhandle structure. Bioconjugate Chem., 30, 931-943. (IF: 4.485)
8. Ong, A.A.L.#, Toh, D.-F.K.#, Patil, K.M.#, Meng, Z., Yuan, Z., Krishna, M.S., Devi, G. Haruehanroengra, P., Lu, Y., Xia, K., Okamura, K., Sheng, J., and Chen, G.* (2019) General recognition of U-G, U-A, and C-G pairs by double-stranded RNA-binding PNAs incorporating an artificial nucleobase. Biochemistry, 58, 1319-1331. (IF: 2.997)
9. Yang, L., Zhong, Z., Tong, C., Jia, H., Liu, Y., and Chen, G.* (2018) Single-molecule mechanical folding and unfolding of RNA hairpins: Effects of single A-U to A∙C pair substitutions and single proton binding and implications for mRNA structure-induced −1 ribosomal frameshifting. J. Am. Chem. Soc. 140, 8172-8184. (IF: 14.357)
10. Patil, K.M.#, Toh, D.-F.K.#, Yuan, Z.#, Meng, Z.#, Shu, Z., Zhang, H., Ong, A.A.L., Krishna, M.S., Lu, L., Lu, Y.,* and Chen, G.* (2018) Incorporating uracil and 5-halouracils into short peptide nucleic acids for enhanced recognition of A-U pairs in dsRNAs. Nucleic Acids Res. 46, 7506-7521. (IF: 11.561)
11. Maraswami, M., Chen, G.,* and Loh, T.-P.* (2018) Iridium(III)-catalyzed selective and mild C-H amidation of cyclic N-sulfonyl ketimines with organic azides. Adv. Synth. Catal. 360, 416-421. (IF: 5.123)
12. Puah, R.Y.#, Jia, H.#, Maraswami, M.#, Toh, D.-F.K.#, Ero, R.#, Yang, L., Patil, K.M., Ong, A.A.L., Krishna, M.S., Sun, R., Tong, C., Huang, M., Chen, X., Loh, T.-P., Gao, Y.G., Liu, D.X.,* and Chen, G.* (2018) Selective binding to mRNA duplex regions by chemically modified peptide nucleic acids stimulates ribosomal frameshift. Biochemistry 57, 149-159. (IF: 2.997)
Invited for the Future of Biochemistry special issue,
Cover highlight of 44 faces representing the Future of Biochemistry,
Editorial
13. Maraswami, M., Pankajakshan, S., Chen, G.,* and Loh, T.-P.* (2017) Palladium-catalyzed direct C-H trifluoroethylation of aromatic amides. Org. Lett. 19, 4223-4226. (IF: 6.492)
14. Chen, H., Jia, H., Tham, H.P., Qu, Q., Xing, P., Zhao, J., Phua, S.Z.F., Chen, G.,* and Zhao, Y.* (2017) Theranostic prodrug vesicles for imaging guided co-delivery of camptothecin and siRNA in synergetic cancer therapy. ACS Appl. Mater. Interfaces 9, 23536-23543. (IF: 8.097)
15. Toh, D.-F.K.#, Patil, K.M.#, and Chen, G.* (2017) Sequence-specific and selective recognition of double-stranded RNAs over single-stranded RNAs by chemically modified peptide nucleic acids. J. Vis. Exp. 127, e56221. (IF: 1.325)
16. Zhong, Z., Yang, L., Zhang, H., Shi, J., Vandana, J., Lam, D.T.U.H., Olsthoorn, R.C.L., Lu, L., and Chen, G.* (2016) Mechanical unfolding kinetics of the SRV-1 gag-pro mRNA pseudoknot: possible implications for −1 ribosomal frameshifting stimulation. Sci. Rep. 6, 39549. (IF: 4.122)
17. Toh, D.-F.K.#, Devi, G.#, Patil, K.M., Qu, Q., Maraswami, M., Xiao, Y., Loh, T.-P., Zhao, Y.,* and Chen, G.* (2016) Incorporating a guanidine-modified cytosine base into triplex-forming PNAs for the recognition of a C-G pyrimidine-purine inversion site of an RNA duplex. Nucleic Acids Res. 44, 9071-9082. (IF: 11.561)
18. Tan, J., Ho, J.X.J., Zhong, Z., Luo, S., Chen, G., and Roca, X.* (2016) Noncanonical registers and base pairs in human 5’ splice-site selection. Nucleic Acids Res. 44, 3980-3921. (IF: 11.561)
19. Guo, S., Kierzek, E., Chen, G., Zhou, Y.J., and Wong, S.K.* (2015) TMV mutants with poly(A) tracts of different lengths demonstrate structural variations in 3′UTR affecting viral RNAs accumulation and symptom expression. Sci. Rep. 5, 18412. (IF: 4.122)
20. Zhong, Z., and Chen, G.* (2015) How RNA catalyzes cyclization. Nat. Chem. Biol. 11, 830-831. (IF: 13.843)
21. Zhong, Z., Soh, L.H., Lim, M.H., and Chen, G.* (2015) A U∙U pair-to-U∙C pair mutation-induced RNA native structure destabilization and stretching-force-induced RNA misfolding. ChemPlusChem 80, 1267-1278. (IF: 3.205)
22. Zhang, L., Liu, H., Shao, Y.,* Lin, C., Jia, H., Chen, G.,* Yang, D.,* and Wang, Y. (2015) Selective lighting up of epiberberine alkaloid fluorescence by fluorophore-switching aptamer and stoichiometric targeting of human telomeric DNA G-quadruplex multimer. Anal. Chem. 87, 730-737. (IF: 6.042)
23. Devi, G.#, Zhou, Y.#, Zhong, Z.#, Toh, D.-F.K.#, and Chen, G.* (2015) RNA triplexes: From structural principles to biological and biotech applications. Wiley Interdiscip. Rev. RNA 6, 111-128. (IF: 5.844)
24. Ma, X.#, Devi, G.#, Qu, Q., Toh, D.-F.K., Chen, G.,* and Zhao, Y.* (2014) Intracellular delivery of antisense peptide nucleic acid by fluorescent mesoporous silica nanoparticles. Bioconjugate Chem. 25, 1412-1420. (IF: 4.485)
25. Devi, G., Yuan, Z., Lu, Y., Zhao, Y.,* and Chen, G.* (2014) Incorporation of thio-pseudoisocytosine into triplex-forming peptide nucleic acids for enhanced recognition of RNA duplexes. Nucleic Acids Res. 42, 4008-4018. (IF: 11.561)
26. Zhou, Y., Kierzek, E., Loo, Z.P., Antonio, M., Yau, Y.H., Chuah, Y.W., Geifman-Shochat, S., Kierzek, R.,* and Chen, G.* (2013) Recognition of RNA duplexes by chemically modified triplex-forming oligonucleotides. Nucleic Acids Res. 41, 6664-6673. (IF: 11.561)
27. Tinoco, I., Jr.,* Chen, G., and Qu, X. (2010) RNA reactions one molecule at a time, in RNA Worlds, (Gesteland, R.F., Cech, T.R., and Atkins, J.F., Eds.), Cold Spring Harbor Laboratory Press. Cold Spring Harb. Perspect. Biol. 2, a003624. doi: 10.1101/cshperspect.a003624. (IF: 9.274)
28. Chen, G., Chang, K.Y., Chou, M.Y., Bustamante, C., and Tinoco, I., Jr.* (2009) Triplex structures in an RNA pseudoknot enhance mechanical stability and increase efficiency of –1 ribosomal frameshifting. Proc. Natl. Acad. Sci. USA 106, 12706-12711. (IF: 9.504)
29. Chen, G., Kennedy, S.D., and Turner, D.H.* (2009) A CA+ pair adjacent to a sheared GA or AA pair stabilizes size-symmetric RNA internal loops. Biochemistry 48, 5738-5752. (IF: 2.997)
30. Chen, G., Wen, J.D., and Tinoco, I., Jr.* (2007) Single-molecule mechanical unfolding and folding of a pseudoknot in human telomerase RNA. RNA 13, 2175-2188. (IF: 4.490)
31. Chen, G., Kierzek, R., Yildirim, I., Krugh, T.R., Turner, D.H.,* and Kennedy, S.D. (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, 6718-6727. (IF: 3.146)
32. Shankar, N., Kennedy, S.D., Chen, G., Krugh, T.R., and Turner, D.H.* (2006) The NMR structure of an internal loop from 23S ribosomal RNA differs from its structure in crystals of 50S ribosomal subunits. Biochemistry 45, 11776-11789. (IF: 2.997)
33. Chen, G., Kennedy, S.D., Qiao, J., Krugh, T.R., and Turner, D.H.* (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, 6889-6903. (IF: 2.997)
34. Chen, G., and Turner, D.H.* (2006) Consecutive GA pairs stabilize medium-size RNA internal loops. Biochemistry 45, 4025-4043. (IF: 2.997)
35. Chen, G., Znosko, B.M., Kennedy, S.D., Krugh, T.R., and Turner, D.H.* (2005) Solution structure of an RNA internal loop with three consecutive GA pairs. Biochemistry 44, 2845-2856. (IF: 2.997)
36. Chen, G., Znosko, B.M., Jiao, X., and Turner, D.H.* (2004) Factors affecting thermodynamic stabilities of RNA 3 × 3 internal loops. Biochemistry 43, 12865-12876. (IF: 2.997)
37. Cui, Y.,* Chen, G., Ren, J., Shao, M., Xie, Y., and Qian, Y.* (2003) Solvothermal syntheses of β-Ag2Se crystals with novel morphologies. J. Solid State Chem. 172, 17-21. (IF: 2.179)
38. Cui, Y.,* Chen, J., Chen, G., Ren, J., Yu, W., and Qian, Y. (2001) Bis(2,2-bipyridine-N,N')tetra-µ-chloro-tetracopper(I). Acta Crystallogr. Sect. C 57, 349-351. (IF: 8.678)
39. Shao, M., Mo, M., Cui, Y., Chen, G., and Qian, Y.* (2001) The effect of agitation states on hydrothermal synthesis of Bi2S3 nanorods. J. Cryst. Growth 233, 799-802. (IF: 1.573)
40. Cui, Y.,* Ren, J., Chen, G., Qian, Y.,* and Xie, Y. (2001) A simple route to synthesize MInS2 (M = Cu, Ag) nanorods from single-molecule precursors. Chem. Lett., (3) 236-237. (IF: 1.485)
41. Cui, Y.,* Ren, J., Chen, G., Yu, W., and Qian Y. (2000) Poly[lead(II)-µ-4,4-bipyridine-N:N'-di-µ-bromo]. Acta Crystallogr. Sect. C 56, E552-E553. (IF: 8.678)
42. Cui, Y., Chen, G., Ren, J., Qian, Y.,* and Huang, J.* (2000) Syntheses, structures and magnetic behaviors of di- and trinuclear pivalate complexes containing both cobalt(II) and lanthanide(III) ions. Inorg. Chem. 39, 4165-4168. (IF: 4.700)
43. Cui, Y.,* Zhang, X., Zheng, F., Ren, J., Chen, G., Qian, Y., and Huang J. (2000) Two mixed-metal carboxylate-base adducts. Acta Crystallogr. Sect. C 56, 1198-1200. (IF: 8.678)