Research Interests
   Our group is interested in exploring molecular mechanisms of human hepatocellular carcinoma (HCC) and research areas are focusing on: tumor microenvironment and cancer metastasis, cancer metabolomics, biomarker, drug discovery, etc.
Using techniques of Marathon-RACE and SMART-RACE, we identified several novel full-length cDNAs involved in hepatocarcinogenesis. We designated these novel genes as BNIPL, LASS2, ANGPTL4, ASB8, and C17orf25, respectively. The detailed and latest information for these novel genes can be found on the HUGO Gene Nomenclature Committee (HGNC) web site (http://www.genenames.org) and in our publications.
In the field of cancer metastasis, we focus on the role of tumor acidic-microenvironment in cancer invasion and metastasis. One of our studies in this area was published recently (Cancer Res 2005, Cancer Res 2007). The articles reveal the relationship between vacuolar H+-ATPases (V-ATPases) and cancer metastasis in HCC. V-ATPases have been proposed to have an important role in tumor metastasis, because they play an essential role in maintaining neural cytosolic pH, very acidic luminal pH, and acidic extracellular pH. Our findings firstly report that the inhibition of V-ATPase function via knockdown of ATP6L (a key subunit of V-ATPase complex) expression using RNA interfering technology can effectively retard the cancer growth and suppress the cancer metastasis by the decrease of proton extrusion and the down-regulation of gelatinase activity. Therefore, our results implicate the potential for cancer treatment using V-ATPase as a candidate target.
Using systems biology approach and cancer metabolomics, our group is currently involved in projects discovering biomarkers of diagnosis and prognosis for HCC and drug targets for cancer treatment.

Area of Expertise
Cancer/Hepatocellular Carcinoma, Tumor Microenvironment, Cancer Metastasis, Cancer Metabolomics, Biomarker, Drug Discovery.

Supports
National Key Basic Research Program of China, 2009CB521803 (PI)
National Key Sci-Tech Special Project of China, 2008ZX10002-019 (Co-PI)
National Natural Science Foundation of China, 30973492 (PI)
Shanghai Municipal Program of International Cooperation in Science and Technology, 08410700900 (PI)

Selected Publications
1) Yu B, Yang X, Xu Y, Yao G, Shu H, Lin B, Hood L, Wang H, Yang S, Gu J, Fan J*, Qin W*. Elevated expression of DKK1 is associated
    withcytoplasmic/nuclear beta-catenin accumulation and poor prognosis in hepatocellular carcinomas. J Hepatol. 2009 May;50(5):
    948-57.
2) You H, Jin J, Shu H, Yu B, De Milito A, Lozupone F, Deng Y, Tang N, Yao G, Fais S, Gu J, Qin W*. Small interfering RNA targeting the
     subunit ATP6L of proton pump V-ATPase overcomes chemoresistance of breast cancer cells. Cancer Lett. 2009 Jul 18;280(1):110-9.
3) Jin J, You H, Yu B, Deng Y, Tang N, Yao G, Shu H, Yang S, Qin W*. Epigenetic inactivation of SLIT2 in human hepatocellular
    carcinomas. Biochem Biophys Res Commun. 2009 Jan 30;379(1):86-91.
4) Sheng SL, Huang G*, Yu B, Qin WX*. Clinical significance and prognostic value of serum Dickkopf-1 concentrations in patients with
     lung cancer. Clin Chem. 2009 Sep;55(9):1656-64.
5) Fais S, De Milito A, You H, Qin W*. Targeting vacuolar H+-ATPases as a new strategy against cancer. Cancer Res. 2007 Nov
     15;67(22):10627-30. Review.
6) Xie L, Qin W*, Li J, He X, Zhang H, Yao G, Shu H, Yao M, Wan D, Gu J. BNIPL-2 promotes the invasion and metastasis of human
     hepatocellular carcinoma cells. Oncol Rep. 2007 Mar;17(3):605-10.
7) Lu X, Qin W*, Li J, Tan N, Pan D, Zhang H, Xie L, Yao G, Shu H, Yao M, Wan D, Gu J, Yang S. The growth and metastasis of human
     hepatocellular carcinoma xenografts are inhibited by small interfering RNA targeting to the subunit ATP6L of proton pump. Cancer Res.
     2005 Aug 1;65(15):6843-9.
8) Xie L, Qin W*, Li JJ, He XH, Shu HQ, Yao GF, Wan DF, Gu JR. cDNA expression array analysis of gene expression in human
     hepatocarcinoma Hep3B cells induced by BNIPL-1. Acta Biochim Biophys Sin (Shanghai). 2005 Sep;37(9):618-24.
9) Wan D#, Gong Y#, Qin W#, Zhang P#, Li J#, Wei L#, Zhou X, Li H, Qiu X, Zhong F, He L, Yu J, Yao G, Jiang H, Qian L, Yu Y, Shu H, Chen
     X, Xu H, Guo M, Pan Z, Chen Y, Ge C, Yang S, Gu J. Large-scale cDNA transfection screening for genes related to cancer development
     and progression. Proc Natl Acad Sci U S A. 2004 Nov 2;101(44):15724-9.
10) Xie L, Qin W*, He XH, Shu HQ, Yao GF, Wan DF, Gu JR. Differential gene expression in human hepatocellular carcinoma Hep3B
      cells induced by apoptosis-related gene BNIPL-2. World J Gastroenterol. 2004 May 1;10(9):1286-91.

Education Background & Academic Experience
1)2003-2009: Postdoctoral Fellow, Institute of Biochemistry, Medical Faculty, University of Cologne, Germany
2)2000-2003: Ph.D, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing
3)1997-2000: M.S., College of Life Science, Nanjing Agriculture University, Nanjing
4)1992-1996: B.S., College of Food Science, Nanjing Agriculture University, Nanjing

Research Interests
It is widely accepted that tumor microenvironment not only passively responds to carcinogenesis, but also actively contributes to tumor initiation, progression, and metastasis. In general, tumor microenvironment includes extracellular matrix (ECM), stromal cells, hypoxia, acidosis, etc. We are interested in tumor-stroma and tumor-ECM interactions in human hepatocellular carcinoma (HCC). After liver injury, activated hepatic stellate cells produce abundant ECM proteins, beneficial (repair and regeneration) or detrimental (cirrhosis and tumor) to the liver. In tumor microenvironment, ECM proteins also have both positive and negative effects on tumor growth by inhibiting or promoting tumor angiogenesis and metastasis. The purpose of our study is to identify ECM proteins as biomarkers of tumor diagnosis, to elucidate the molecular mechanism of ECM proteins on tumor progression, and eventually to determine them as potential therapeutic targets of HCC.

Area of Expertise
Hepatocellular Carcinoma, Tumor Microenviroment, Extracellular Matrix, Hepatic Stellate Cells.

Selected Publications
1) Has C, Herz C, Zimina E, Qu HY, He Y, Zhang ZG, Wen TT, Gache Y, Aumailley M, Bruckner-Tuderman L. Kindlin-1 is required for
     RhoGTPases-mediated lamellipodia formation in keratinocytes. Am J Pathol. (2009), 175, 1442-1452
2) Zhi-Gang Zhang, Ingo Bothe, Frank Hirche, Manon Zweers, Donald Gullberg, Gabriele Pfitzer, Thomas Krieg, Beate Eckes and Monique
    Aumailley. Interactions of primary fibroblasts and keratinocytes with extracellular matrix proteins: contribution of 21 integrin. J Cell Sci.
    (2006), 119, 1886-1895
3) Z.-G. Zhang, C.A. Lambert, S. Servotte, G. Chometon, B. Eckes, T. Krieg, C.M. Lapière, B.V. Nusgens and M.Aumailley. Effects of
    constitutively active GTPases on fibroblast behavior. Cell. Mol. Life Sci.(2006), 63, 0082–0091
4) Beate Eckes, Manon C Zweers, Zhi Gang Zhang, Ralf Hallinger, Cornelia Manch Monique Aumailley Thomas Krieg. Mechanical
    Tension and Integrin alpha2beta1 Regulate Fibroblast Functions. J Invest Dermatol. 2006 Sep;126 Suppl:66-72
5) Gretel Chometon, Zhi-Gang Zhang, Eric Rubinstein, Claude Boucheix, Cornelia Mauch, Monique Aumailley. Dissociation of the complex
     between CD151 and laminin-binding integrins permits migration of epithelial cells. Exp. Cell Res. (2006), 312, 983-995
6) Servotte S., Zhang Z.-G., Lambert C.A., Ho T.T.G., Chometon G., Eckes B., Krieg T., Lapière C.M., Nusgens B.V., Aumailley M.
     Establishment of stable human fibroblast cell lines constitutively expressing active Rho-GTPases. Protoplasma, 2006, 229, 215-220
     (Co-first author).
7) Zhi-Gang Zhang, Hua-Lin Zhou, Tao Chen, Yan Gong, Wan-Hong Cao, Yu-Jun Wang, Jin-Song Zhang and Shou-Yi Chen. Evidence for
    Serine/Threonine and Histidine Kinase Activity in the Tobacco Ethylene Receptor Protein NTHK2.Plant Physiol. (2004), 136,
    2971–2981
8) Zhi-Gang Zhang, GONG Yan, HE Xin-Jian, WANG Yu-Jun, SUN Zhong-Xu, ZHANG Jin-Song*, CHEN Shou-Yi*. Cloning of
    the full-length gene for tobacco ethylene receptor NTHK2 and characterization of its kinase domain.Acta Botanica Sinica (2003), 45
     (1):68-72
9) Zhi-Gang Zhang, RUI Qi, Xu Lang-Lai. Relationship between endopeptidase and H2O2 during the aging of wheat leaf. Acta Botanica
     Sinica (2001), 43, 127-131

Lab Members
Ronghu Ke, Ph. D., Research Scientist. +86-21-64436572
Aiyun Guo, M. Sc., Research Associate. +86-21-34206022
Genfu Yao, B. Sc., Senior Technician. +86-21-64436572
Huiqun Shu, B. Sc., Technician. +86-21-64436793
Wei Chu, +86-21-64436572

Graduate Students
Yongdong Niu, Ph. D. student, Shanghai Jiao Tong University. +86-21-64436572
Shaohua Fan, Ph. D. student, Shanghai Jiao Tong University. +86-21-64436572
Yun Deng, Graduate student, Shanghai Jiao Tong University. +86-21-64436572
Qiujin Shen, Graduate student, Shanghai Jiao Tong University. +86-21-34206022
Zheng Wu, Graduate student, Fudan University. +86-21-34206022