Department of Biophysics and Structural Biology

Department of Biophysics and Structural biology provides graduate and undergraduate training in cellular and molecular biophysics, method of modern biophysics, proteomics and cell ultramicrostructure. Areas of research interests include (1) development of novel bioanalytical methods; (2) application of modern biophysics methods to study macromolecule assembly, protein-protein interaction, and screen biomarkers; (3) cancer immunotherapy and vaccine development

Zhili Li, Professor of mass spectrometry and biophysics, Ph.D.

Contact information:
E-mail: lizhili@ibms.pumc.edu.cn
Voice: 86-10-65296475
Fax: 86-10-65296475

Ph.D. in physical chemistry at Changchun Institute of Applied chemistry, the Chinese Academy of Sciences, Changchun, China
Postdoctoral fellow at Analytical Center, China pharmaceutical University, Nanjing, China.
Postdoctoral Associate, Associate Research Scientist at Department of Pharmacology, Yale University, New Haven. USA
.
Research interests of Professor Li’Group
Our goals are to use and develop novel bioanalytical tools, specifically within the field of mass spectrometry and chromatography, to address the important clinical questions. Our current research interests include (1) the development of techniques and methods for clinical proteomic analysis, using 1- and 2-dimensional gel electrophoresis and micro/nano-chromatography for protein separation; (2) the application of micro/nano-chromatographic separation techniques for the study of serum and plasma proteomics of the important diseases; (3) the application of an integrated reliable, easy-to-use automated mass spectrometry-based platform for non-abundance protein characterization of serum and plasma; (4) the development of biochemical methods used to isolated protein assemblies, such as ubiquitin-proteasome complexes, systematic analysis of noncovalent protein complexes to chart native biological relevant protein-protein interactions, characterize the components by mass spectrometry (MS); (4) the development and application of bioanalytical methods for the structural characterization of proteins and post-translational modifications, (6) biomarker screening of cancer, such as pancreatic cancer using the novel proteomic techniques.

Current Group Members

Technican

Yanchun Deng

Graduate students

Haijing Zhang, Guoqiang Chen, Xinli Wang, Hui Liu, Liyan Lv, Peixuan Pi, Lei Cui, Zhiyun Zhao, Wan Wang

Selected Publications

 

  1. Zhili Li, Apurba K. Sau, Cristina M. Furdui and Karen S. Anderson*, Probing the role of tightly bound phosphoenolpyruvate in Escherichia coli 3-deoxy-d-manno-octulosonate 8-phosphate synthase catalysis using quantitative time-resolved electrospray ionization mass spectrometry in the millisecond time range, Analytical Biochemistry, 2005, 343(1), 35-47.
  2. Apurba K. Sau, Zhili Li and Karen S Anderson*, Probing the role of metal ions in the catalysis of Helicobacter pylori 3-deoxy-D-manno-octulosonate-8-phosphate synthase using a transient kinetic analysis, The Journal of Biological Chemistry， 2004, 279(16), 15787-15794.
  3. Zhili Li*, Shuying Liu, Substituent Effect on Ion-Molecule Reaction of Disubstituted Benzenes with Acetone Plasma, International Journal of Mass Spectrometry, 2004, 231, 69-75.
  4. Zhili Li, Apurba Sau, Shida Shen, Craig Whitehouse, Timor Baasov and Karen S. Anderson* , A snapshot of enzyme catalysis using electrospray ionization mass spectrometry, Journal of the American Chemical Society，2003,125, 9938-9939.
  5. Ding Gang*, Dong Zibo, Zhili Li, Longsheng Sheng, Bingren Xiang and Dengkui An, Biochromatography and its application in pharmaceutical research, Journal of China pharmaceutical University, 2002, 33(4), 354-357
  6. Zhili Li*, Fengrui Song, Shuying Liu, Studies of the ortho effect in fragmentations of acetyl ion adducts of disubstituted benzenes, Rapid Communications in Mass Spectrometry, 2001, 15, 1893-1898.
  7. Li Zhili*, Song Fengrui, Liu Shuying, H/D exchange reaction of cyclopropane derivatives in the ion system of CD3OD, Chinese Journal of Analytical Chemistry, 2001, 29(1), 23-27.
  8. Ji, Kejian; Liu, Yuanjun; Zhang, Yinsheng; Li, Zhili; Zhang, Songqing; Yu, Yanhua.  NMR characterization of polyunsaturated fatty acid ethyl ester in fish oils. Huaxue Fenxi Jiliang,  2001, 10(3), 3-8.
  9. Li Zhili*, Liu Shuying, Long Longsheng, Fragmentation reactions of Adduct Ions [M + CH3CO]+ of Isomeric Phenylenediamines, Journal of Chinese Mass Spectrometry Society, 2000, 20(3), B14-18.
  10. Zhili Li*, Studies on the Adduct Reactions of Bisubstituted Benzenes in Ion System of Acetyl chloride in the Gas Phase, Chemical Research in Chinese Universities，2000, 16(4), 334-340.
  11. Zhili Li*, Shuying Liu, Hydrogen-deuterium exchange reactions of cis- and trans-cyclopropane derivatives with D2O and CD3OD in the gas phase, Rapid Communications in Mass Spectrometry, 2000, 14, 180-187.

 

Tumor Virus Research Group

Xuemei Xu, Ph.D
Professor
Ph.D University of Peking Union Medical College
Cancer Immunotherapy and Vaccine Development
The squamous epithelia of man could be infected by human papillomaviruses (HPVs). Certain types of HPVs (for instance, HPV6, HPV11) generally induce localized benign proliferation. However, the lesions induced by HPVs, such as HPV16, HPV18, HPV31, HPV45 and HPV58 might undergo malignant change. There is a strong association between malignant progression of human genital lesions and certain HPV types, most frequently HPV16.
The major goals of this laboratory are to elucidate the role of HPVs in carcinogenesis, to develop a safe and effective vaccine for prevention and treatment of malignancy induced by genital HPV.
Cervical cancers enable to express unique tumor-specific or tumor-associated antigens, E6 and E7 are consistently expressed in HPV-associated lesions and are responsible for malignant transformation of infected cells. The therapeutic vaccines developed in this laboratory were E7 based naked DNA vaccines, chimeric virus-like particle vaccine, or recombinant protein vaccine. It’s difficult in studying HPV virions, due to lack of efficient methods in vitro, however, this problem was partially overcome by the fact that virion proteins can –ssemble by itself into virus-like particles (VLPs) when they were over-expressed in eukaryotic cells. We have developed a variety of VLPs of different kind of HPVs, proved to be highly immunogenetic in mice and rabbit modelshave been developed in this laboratory. Chimeric VLPs, bearing the cervical cancer specific antigens and immune stimulating molecular have been investigated. The biological and chemical studies of VLPs are also on going.
A variety of techniques including advanced cell culture, cellular immunology including cyto-fluorometry, molecular biology and immunoc-histochemistry have been adopted. Overall the research program will lead to a fundamental understanding of virus-host interactions, antigen presentation, tumor-immune system interactions and the design of effective immunotherapeutic approaches for cancers stated in above and possibly also for other types of cancer.
Other Research Interests

  • Cancer Vaccines
  • Cancer Immunotherapy
  • Tumor Immunology
  • Tumor Immune Escape Mechanisms
  • Viral Immunology

Selected Publications

Joeli A. Brinkman, Xuemei Xu, and W. Martin Kast. The efficacy a DNA vaccine containing inserted and replicated regions of the E7 gene for treatment of HPV 16 induced tumors. Vaccine, 2007, in press.
Y.-F. Xu, Q.-Y. Wang, H.-Tao.Zhang,Y.-H. Han, Xuemei Xu*. The artificial HPV16 mE7 protein can be encapsidated in HPV6b L1/L2 Virus-Like Particles. Chinese Medical Journal (CMJ) 2007, in press.
Y.-F. Xu, Y.-Q. Zhang, X.-M. Xu*, and G.-X. Song. Papillomavirus virus-like particles as vehicles for the delivery of epitopes or genes. Arch Virol 2006，PMID: 16791442 published online.
Li,D-D., Gal,V., Alegre,M-L., Chong,A.S.F., Chen, L., Shao, Q., Xu,X., Koreny,T., Mikecz,K., Finnegan,A, Glant,T.T., Zhang,J.: Cutting Edge: Cbl-b: One of the key molecules tunning CD28-and CTLA-4-mediated T cell costimulation. J.Immunol. 2004,173:7135.
Zhao Xin, Xu Xuemei*, Song Guoxing. Heat shock proteins and immunotherapy. J Microbiol Immunol. 2005, 3 (1): 1-14.
Jian Zhang，Xuemei Xu, Yong Liu. Activation-induced cell death in T cells and autoimmunity. Cellular & Molecular Immunology. 2004,1(3): 186-192.
Xuemei Xu, Guoxing Song, Mingzao Zhu, Jingyi Si, Kun Li. The study on the immune responses induced by human papillomavirus type 16 modified E6E7 gene. Basic Medical Sciences and Clinics. 2003, 23(3): 269-273.
Mingzhao Zhu, Xuemei Xu, Liu Hongwei, Yang Baoling, Guoxing Song. Enhancement of DNA vaccine potency against herpes simplex virus-1 by co-administration of interleukin-18 expression plasmid as genetic adjuvant. Journal Medicine Micrology. 2003, 52(3): 223-228.
Xuemei Xu, Mingzao Zhu, Guoxing Song, Jingyi Si, Kun Li. Coimmunization B7-1 co-stimulating genes enhanced human papillomavirus type 16 E6E7 DNA vaccine-induced specific immune responses. Acta Academiae Medicine Science. 2003,25(3):301-306.

Xuemei Xu Progress in the papillomavrus therapeutic vaccines. Jounal of Cellular and Molecular Immunology. 2003,19(3):20-23.

Xuemei Xu, Mingce Zhang, Liqun Luo, Xiaojuan Liu, Mingzhao Zhu, Guoxing Song. Analysis of the transformation activity and the immunogenicity of a human papillomavirus type 16 variant E6E7 gene from a cervical carcinoma biopsy in Shangdong province. Chinese Journal of Microbiology and Immunology. 2002, 22(4):431-436.

Xuemei Xu, Guoxing Song, Jingyi Si. Progress in the mechanism study of DNA vaccine. Progress in Microbiology and Immunology. 2002, 30(1): 65-70.
Xuemei Xu, Guoxing Song, Jingyi Si. Sequence analysis of human papillomavirus type 16 E6E7 gene from cervical carcinoma biopsies of Chinese patients in Shandong province. Chinese J. Biomed. Eng, 2000,9(2):56-60.
Xuemei Xu, Jingyi Si, Shide Liu, Jianqing Xu, Zhaoqi Liu, Kun Li, Hao Chen, Guoxing Song. Isolating, cloning and sequencing of HPV16E6E7 gene from a cervical carcinoma biopsy in Shandong province. Acta Academiae Medicine Science. 1999,12(3):185-191.
Weiming Zhao, Xuemei Xu, Yabing Zhou, et al. Cloning and SSCP analysis of human papillomavirus type 16 E6 from cervical carcinomas in Chinese. Basic Medical Sciences and Clinics. 1999,19(4):86-91.
Jianqing Xu, Jingyi Si, Youhui Zhang, Guoxing Song, Shide Liu, Xuemei Xu, Tao Song. Human papillomavirus 16 E7-specific CTL induction through mouse B7-1 costimulating with E7C subgene. Chinese J Microbiol Immunol. 1999,19(3):227-231.
Chaoqi Liu, Jingyi Si, Shide Liu, Xuemei Xu, Guoxing Song, Kun Li. Cloning of human papillomavirus type16 E7 gene and expression in E.coli. Acta Academiae Medicine Science. 1998,20(3):167-172.
Xuemei Xu, Jingyi,Si, Shifang Zhou, Shide Liu, Kun Li, Guoxing Song. Simultaneous detection of human papillomavirus and chlamydia trachomatis with two sets of primes polymerase chain reaction. Chinese Journal of Microbiology and Immunology. 1997, (17): 471-474.

 

Grants:

Key Program of China International Science & Technology corporation (2005DFA30070) Development of a multi-valent vaccine to prevent infection of human papillomavirus. (Principal investigator)

Natural Scientific Foundation of China (30472002): Anti-tumor immune response with HPV16E7 DNA vaccines and co-administration of CD40LT as genetic adjuvant. (Principal Investigator)

National Natural Scientific Foundation of China (30271355): The study on induction of immune response with HPV16 E6E7/HSP70 DNA and IL-15 co-administration. (Principal Investigator)

National High-Tech R&D Program of China (2001AA215221): The research on the vaccines against HPV. (Principal Investigator)

National High-Tech R&D Program of China (2004AA215181): The research on the vaccines against HPV. (Principal Investigator)

National Natural Scientific Foundation of China:The study on anti-tumor immune responses induced by co-administration of B7-1 gene and mutated E6E7 genes of HPV16. (Principal Investigator)