Xian en ZHANG

Title: Principle Investigator E-mail: x.zhang@wh.iov.cn


Xian-En Zhang received his first degree in Hubei University in 1982, MPhil. (microbiology, 1985) and Ph.D. (biochemistry, 1995) in the Chinese Academy of Science (CAS).

Research Interests

1) Nanobiology

we have exploited macrobiomolecules, such as viral capsid proteins and microbial surface layer proteins, as building blocks for construction of nanostructures with designed functions, e.g. biosensing and drug carriers. The current interest focuses on profiling cell surface proteins at super resolution level.

2) Sensing molecular events in living cells

we have developing red, far red and near infrared fluorescent protein molecular sensing systems (BiFC, TriFC, etc.) and "color virus" to achieve the visualization of molecular interactions in living cells and in vivo. The current interests include constructing cell sensors for detection of toxicity of chemicals at subcellular level and building molecular sensors for study of 3D genomics.

3) Biosensors

We have developed a series of biosensor and biochips, including microbial sensors, multiple/cascade enzyme electrodes, gene optode, Mycobacterium tuberculosis proteome microarray for environmental monitoring, bioprocess control, clinical diagnosis and new biomarkers screening. The current study emphasizes portability and flexibility of biosensors.

4) Microbial enzymology for biosensors

we have exploited and engineered a number of microbial enzymes to built some unique methods for improving biosensor performance, e.g. orientation control of enzyme immobilization, homogeneity of biosensor surface, enhanced electron transfer between enzyme molecules and the electrode, cascade enzyme sensors, etc. We continue to promote the research in this area.


1. Xianxun Sun, Wei Li, Xiaowei Zhang, Mi Qi, Zhiping Zhang, Xian-En Zhang*, Zongqiang Cui*(2016). In Vivo Targeting and Imaging of Atherosclerosis Using Multifunctional Virus-Like Particles of Simian Virus 40. NANO LETTERS, 16:6164?6171.

2. Yingxin Ma, Zhike He, Tianwei Tan, Wei Li, Zhiping Zhang, Shuang Song, Xiaowei Zhang, Qinxue Hu, Peng Zhou, Yuntao Wu, Xian-En Zhang*, and Zongqiang Cui*(2016). Real-Time Imaging of Single HIV-1 Disassembly with Multicolor Viral Particles. ACS NANO, 10: 6273?6282.

3. Minghai Chen, Sanying Liu, Wei Li, Zhiping Zhang, Xiaowei Zhang, Xian-En Zhang*, Zongqiang Cui*(2016). Three-Fragment Fluorescence Complementation Coupled with Photoactivated Localization Microscopy for Nanoscale Imaging of Ternary Complexes. ACS NANO, 10: 8482?8490.

4. Dong Men*, Juan Zhou, Wei Li, Yan Leng, Xinwen Chen, Sheng-ce Tao, Xian-En Zhang*(2016). Fluorescent Protein Nanowire-Mediated Protein Microarrays for Multiplexed and Highly Sensitive Pathogen Detection. ACS APPLIED MATERIALS & INTERFACES, 8:17472-17477.

5. Xian-En Zhang*, Zongqiang Cui, Dianbing Wang(2016). Sensing of biomolecular interactions using fluorescence complementing systems in living cells. Biosensors and Bioelectronic, 76:243-250.

6. Yingxin Ma, Zongqiang Cui, Zhike He, Wei Li, Zhi-Ping, Zhang, Xiaowei Zhang, Xian-En Zhang*, Tianwei Tan*(2016). Delaying Photobleaching of a Light-Switch Complex for Real-Time Imaging of Single Viral Particle Uncoating. ANALYTICAL CHEMISTRY, 88:10675-10679.

7. Ting Wang, Zhenhua Zheng, Xian-En Zhang*, Hanzhong Wang*(2016). Quantum dot-fluorescence in situ hybridisation for Ectromelia virus detection based on biotin-streptavidin interactions. TALANTA, (2016)179–184.

8. ZhaoYang Li, ZhiPing Zhang, LiJun Bi, ZongQiang Cui, JiaoYu Deng, DianBing Wang*, Xian-En Zhang* (2016). Mutagenesis of mNeptune Red-Shifts Emission Spectrum to 681-685 nm. PLOS ONE, 11(4):e0148749.   

9. D. Men, T. T. Zhang, L. W. Hou, J. Zhou, Z. P. Zhang, Y. Y. Shi, J. L. Zhang, Z. Q. Cui, J. Y. Deng, D. B. Wang and X. E. Zhang* (2015) Self-Assembly of Ferritin Nanoparticles into an Enzyme Nanocomposite with Tunable Size for Ultrasensitive Immunoassay. ACS Nano 9(11), 10852-10860.

10. Chuangyan Li, Feng Li*, Yejun Zhang, Wenjing Zhang, Xian-En Zhang, Qiangbin Wang* (2015). Real-time monitoring surface chemistry-dependent in vivo behaviors of protein nanocages via encapsulating an NIR-II Ag2S quantum dot, ACS nano 9(12), 12255-12263.

11. X. L. Zhang, D. F. Li, J. Fleming, L. W. Wang, Y. Zhou, D. C. Wang, X. E. Zhang* and L. J. Bi* (2015) Core component EccB1 of the Mycobacterium tuberculosis type VII secretion system is a periplasmic ATPase. FASEB J 29(12), 4804-4814.

12. X. Y. Wang, D. B. Wang*, Z. P. Zhang, L. J. Bi, J. B. Zhang, W. Ding and X. E. Zhang* (2015) A S-Layer Protein of Bacillus anthracis as a Building Block for Functional Protein Arrays by In Vitro Self-Assembly. Small 11(43), 5826-5832

13. D. B. Wang, B. Tian, Z. P. Zhang, X. Y. Wang, J. Fleming, L. J. Bi, R. F. Yang and X. E. Zhang* (2015) Detection of Bacillus anthracis spores by super-paramagnetic lateral-flow immunoassays based on "Road Closure". Biosens Bioelectron 67, 608-614.

14. M. Chen, W. Li, Z. Zhang, S. Liu, X. Zhang, X. E.* Zhang and Z. Cui* (2015) Novel near-infrared BiFC systems from a bacterial phytochrome for imaging protein interactions and drug evaluation under physiological conditions. Biomaterials 48, 97-107.

15. Q. Dong, J. Wang, H. Yang, C. Wei, J. Yu, Y. Zhang, Y. Huang, X. E. Zhang* and H. Wei* (2015) Construction of a chimeric lysin Ply187N-V12C with extended lytic activity against staphylococci and streptococci. Microb Biotechnol 8(2), 210-220.

16. S. Fan, D. F. Li, D. C. Wang, J. Fleming, H. Zhang, Y. Zhou, L. Zhou, J. Zhou, T. Chen, G. Chen, X. E. Zhang* and L. Bi* (2015) Structure and function of Mycobacterium smegmatis 7-keto-8-aminopelargonic acid (KAPA) synthase. Int J Biochem Cell Biol 58, 71-80.

17. S. H. Fan, Y. Zhou, H. T. Zhang, J. Fleming, Z. N. Yu, X. E. Zhang* and L. J. Bi* (2015) MutM Interaction Partners Detected in Mycobacterium smegmatis by Tandem Affinity Purification. Progress in Biochemistry and Biophysics 42(10), 935-946.

18. Z. Chen, M. K. Yang, C. Y. Li, Y. Wang, J. Zhang, D. B. Wang, X. E. Zhang* and F. Ge* (2014) Phosphoproteomic analysis provides novel insights into stress responses in Phaeodactylum tricornutum, a model diatom. J Proteome Res 13(5), 2511-2523.

19. J. Deng, L. Bi, L. Zhou, S. J. Guo, J. Fleming, H. W. Jiang, Y. Zhou, J. Gu, Q. Zhong, Z. X. Wang, Z. Liu, R. P. Deng, J. Gao, T. Chen, W. Li, J. F. Wang, X. Wang, H. Li, F. Ge, G. Zhu, H. N. Zhang, J. Gu, F. L. Wu, Z. Zhang, D. Wang, H. Hang, Y. Li, L. Cheng, X. He, S. C. Tao* and X. E. Zhang* (2014) Mycobacterium tuberculosis proteome microarray for global studies of protein function and immunogenicity. Cell Rep 9(6), 2317-2329.

20. Y. Han, S. Wang, Z. Zhang, X. Ma, W. Li, X. Zhang, J. Deng, H. Wei, Z. Li, X. E. Zhang* and Z. Cui* (2014) In vivo imaging of protein-protein and RNA-protein interactions using novel far-red fluorescence complementation systems. Nucleic Acids Res 42(13), e103.

21. F. Li, H. Chen, L. Ma, K. Zhou, Z. P. Zhang, C. Meng, X. E. Zhang* and Q. Wang* (2014) Insights into stabilization of a viral protein cage in templating complex nanoarchitectures: roles of disulfide bonds. Small 10(3), 536-543.

22. Z. Y. Li, D. B. Wang, Z. P. Zhang, L. J. Bi, Z. Q. Cui, J. Y. Deng and X. E. Zhang* (2014) The S28H mutation on mNeptune generates a brighter near-infrared monomeric fluorescent protein with improved quantum yield and pH-stability. Acta Biochim Biophys Sin 46,802-809.

23. F. Liu, J. Gu, X. Wang, X. E. Zhang* and J. Deng* (2014a) Acs is essential for propionate utilization in Escherichia coli. Biochem Biophys Res Commun 449(3), 272-277.

24. F. Liu, M. Yang, X. Wang, S. Yang, J. Gu, J. Zhou, X. E. Zhang*, J. Deng* and F. Ge* (2014b) Acetylome analysis reveals diverse functions of lysine acetylation in Mycobacterium tuberculosis. Mol Cell Proteomics 13(12), 3352-3366.

25. F. Zhao, X. D. Wang, L. N. Erber, M. Luo, A. Z. Guo, S. S. Yang, J. Gu, B. J. Turman, Y. R. Gao, D. F. Li, Z. Q. Cui, Z. P. Zhang, L. J. Bi, A. D. Baughn, X. E. Zhang* and J. Y. Deng* (2014) Binding pocket alterations in dihydrofolate synthase confer resistance to para-aminosalicylic acid in clinical isolates of Mycobacterium tuberculosis. Antimicrob Agents Chemother 58(3), 1479-1487.

Selected papers before 2014

1. D. Gao, Z. P. Zhang, F. Li, D. Men, J. Y. Deng, H. P. Wei, X. E. Zhang* and Z. Q. Cui* (2013) Quantum dot-induced viral capsid assembling in dissociation buffer. Int J Nanomedicine 8, 2119-2128.

2. F. Li, J. Yu, Z. Zhang, Z. Cui, D. Wang, H. Wei* and X. E. Zhang* (2013) Use of hGluc/tdTomato pair for sensitive BRET sensing of protease with high solution media tolerance. Talanta 109, 141-146.

3. D. B. Wang, B. Tian, Z. P. Zhang, J. Y. Deng, Z. Q. Cui, R. F. Yang, X. Y. Wang, H. P. Wei and X. E. Zhang* (2013) Rapid detection of Bacillus anthracis spores using a super-paramagnetic lateral-flow immunological detection system. Biosens Bioelectron 42, 661-667.

4. R. B. Yang, L. J. Bi* and X. E. Zhang* (2013) A novel T-type overhangs improve the enzyme-free cloning of PCR products. Mol Biotechnol 55(1), 10-16.

5. J. Yin, D. Zhu, Z. Zhang, W. Wang, J. Fan, D. Men, J. Deng, H. Wei, X. E. Zhang* and Z. Cui* (2013) Imaging of mRNA-protein interactions in live cells using novel mCherry trimolecular fluorescence complementation systems. PLoS One 8(11), e80851.

6. H. Zhang, D. Li, L. Zhao, J. Fleming, N. Lin, T. Wang, Z. Liu, C. Li, N. Galwey, J. Deng, Y. Zhou, Y. Zhu, Y. Gao, T. Wang, S. Wang, Y. Huang, M. Wang, Q. Zhong, L. Zhou, T. Chen, J. Zhou, R. Yang, G. Zhu, H. Hang, J. Zhang, F. Li, K. Wan, J. Wang, X. E. Zhang* and L. Bi* (2013) Genome sequencing of 161 Mycobacterium tuberculosis isolates from China identifies genes and intergenic regions associated with drug resistance. Nat Genet 45(10), 1255-1260.

7. Q. F. Zhang, J. Gu, P. Gong, X. D. Wang, S. Tu, L. J. Bi, Z. N. Yu, Z. P. Zhang, Z. Q. Cui, H. P. Wei, S. C. Tao, X. E. Zhang* and J. Y. Deng* (2013) Reversibly acetylated lysine residues play important roles in the enzymatic activity of Escherichia coli N-hydroxyarylamine O-acetyltransferase. FEBS J 280(9), 1966-1979.

8. J. Yu, M. Guan, F. Li, Z. Zhang, C. Wang, C. Shu*, H. Wei* and X. E. Zhang* (2012) Effects of fullerene derivatives on bioluminescence and application for protease detection. Chem Commun (Camb) 48(89), 11011-11013.

9. F. Li, Y. Chen, H. Chen, W. He, Z. P. Zhang, X. E. Zhang* and Q. Wang* (2011) Monofunctionalization of protein nanocages. J Am Chem Soc 133(50), 20040-20043.

10. X. D. Wang, J. Gu, T. Wang, L. J. Bi, Z. P. Zhang, Z. Q. Cui, H. P. Wei, J. Y. Deng* and X. E. Zhang* (2011) Comparative analysis of mycobacterial NADH pyrophosphatase isoforms reveals a novel mechanism for isoniazid and ethionamide inactivation. Mol Microbiol 82(6), 1375-1391.

11. F. Li, D. Gao, X. Zhai, Y. Chen, T. Fu, D. Wu, Z. P. Zhang, X. E. Zhang* and Q. Wang* (2011) Tunable, discrete, three-dimensional hybrid nanoarchitectures. Angew Chem Int Ed Engl 50(18), 4202-4205.

12. Y. Liang, Z. Zhang, H. Wei, Q. Hu, J. Deng, D. Guo, Z. Cui* and X. E. Zhang* (2011) Aptamer beacons for visualization of endogenous protein HIV-1 reverse transcriptase in living cells. Biosens Bioelectron 28(1), 270-276.

13. R. Z. Hao, H. B. Song, G. M. Zuo, R. F. Yang, H. P. Wei, D. B. Wang, Z. Q. Cui, Z. Zhang*, Z. X. Cheng* and X. E. Zhang* (2011) DNA probe functionalized QCM biosensor based on gold nanoparticle amplification for Bacillus anthracis detection. Biosens Bioelectron 26(8), 3398-3404.

14. Y. Leng, H. P. Wei, Z. P. Zhang, Y. F. Zhou, J. Y. Deng, Z. Q. Cui, D. Men, X. Y. You, Z. N. Yu, M. Luo and X. E. Zhang* (2010) Integration of a fluorescent molecular biosensor into self-assembled protein nanowires: a large sensitivity enhancement. Angew Chem Int Ed Engl 49(40), 7243-7246.

15. H. Han, Z. Q. Cui, W. Wang, Z. P. Zhang, H. P. Wei, Y. F. Zhou and X. E. Zhang* (2010) New regulatory mechanisms for the intracellular localization and trafficking of influenza A virus NS1 protein revealed by comparative analysis of A/PR/8/34 and A/Sydney/5/97. J Gen Virol 91(Pt 12), 2907-2917.

16. F. Li, Z. P. Zhang, J. Peng, Z. Q. Cui, D. W. Pang, K. Li, H. P. Wei, Y. F. Zhou, J. K. Wen and X. E. Zhang* (2009) Imaging viral behavior in Mammalian cells with self-assembled capsid-quantum-dot hybrid particles. Small 5(6), 718-726.

17. D. Men, Y. C. Guo, Z. P. Zhang, H. P. Wei, Y. F. Zhou, Z. Q. Cui, X. S. Liang, K. Li, Y. Leng, X. Y. You and X. E. Zhang* (2009) Seeding-induced self-assembling protein nanowires dramatically increase the sensitivity of immunoassays. Nano Lett 9(6), 2246-2250.

18. W. Wang, Z. Q. Cui, H. Han, Z. P. Zhang, H. P. Wei, Y. F. Zhou, Z. Chen and X. E. Zhang* (2008) Imaging and characterizing influenza A virus mRNA transport in living cells. Nucleic Acids Res 36(15), 4913-4928.

19. J. Y. Fan, Z. Q. Cui, H. P. Wei, Z. P. Zhang, Y. F. Zhou, Y. P. Wang and X. E. Zhang* (2008) Split mCherry as a new red bimolecular fluorescence complementation system for visualizing protein-protein interactions in living cells. Biochem Biophys Res Commun 367(1), 47-53.

20. S. H. Wang, J. B. Zhang, Z. P. Zhang, Y. F. Zhou, R. F. Yang, J. Chen, Y. C. Guo, F. You and X. E. Zhang* (2006) Construction of single chain variable fragment (ScFv) and BiscFv-alkaline phosphatase fusion protein for detection of Bacillus anthracis. Anal Chem 78(4), 997-1004.

21. F. You, Y. F. Zhou, X. E. Zhang, Z. Huang, L. J. Bi, Z. P. Zhang, J. K. Wen, Y. Y. Chen, G. B. Jiang and M. H. Zheng* (2006) Cell-free bioassay for measurement of dioxins based on fluorescence enhancement of fluorescein isothiocyanate-labeled DNA probe. Anal Chem 78(20), 7138-7144.

22. Y. C. Guo, Y. F. Zhou, X. E. Zhang*, Z. P. Zhang, Y. M. Qiao, L. J. Bi, J. K. Wen, M. F. Liang and J. B. Zhang (2006) Phage display mediated immuno-PCR. Nucleic Acids Res 34(8), e62.

23. L. J. Bi, Y. F. Zhou, X. E. Zhang*, J. Y. Deng, J. K. Wen and Z. P. Zhang (2005) Construction and characterization of different MutS fusion proteins as recognition elements of DNA chip for detection of DNA mutations. Biosens Bioelectron 21(1), 135-144.

24. Z. Q. Cui, Z. P. Zhang, X. E. Zhang*, J. K. Wen, Y. F. Zhou and W. H. Xie (2005) Visualizing the dynamic behavior of poliovirus plus-strand RNA in living host cells. Nucleic Acids Res 33(10), 3245-3252.

25. J. Y. Deng, X. E. Zhang*, Y. Mang, Z. P. Zhang, Y. F. Zhou, Q. Liu, H. B. Lu and Z. J. Fu (2004) Oligonucleotide ligation assay-based DNA chip for multiplex detection of single nucleotide polymorphism. Biosens Bioelectron 19(10), 1277-1283.

26. J. X. Shi, X. E. Zhang*, W. H. Xie, Y. F. Zhou, Z. P. Zhang, J. Y. Deng, A. E. Cass, Z. L. Zhang, D. W. Pang and C. G. Zhang (2004) Improvement of homogeneity of analytical biodevices by gene manipulation. Anal Chem 76(3), 632-638.

27. S. H. Wang, J. K. Wen, Y. F. Zhou, Z. P. Zhang, R. F. Yang, J. B. Zhang, J. Chen and X. E. Zhang* (2004) Identification and characterization of Bacillus anthracis by multiplex PCR on DNA chip. Biosens Bioelectron 20(4), 807-813.