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葛高翔


研究员,研究组长,博士生导师
电话:54921105
E-mail: gxge@@sibcb.ac.cn

 

个人简介:

 1992年-1996年南京大学生物化学系,理学学士;1996年-2001年中国科学院上海生物化学研究所,理学博士;2001年-2002年University of Tennessee Health Science Center,博士后;2002年-2007年University of Wisconsin-Madison,先后为博士后,Scientist;2007年起任中国科学院上海生物化学与细胞生物学研究所研究员,研究组长。

研究方向:

细胞微环境对肿瘤发生及转移的调控

研究工作:

 细胞对外界刺激的反应不仅取决于细胞本身特性,同时也受到细胞微环境(microenvironment)的调节。以上皮细胞为例,其细胞微环境包括细胞外基质(Extracellular Matrix, ECM),生长因子/激素,蛋白酶等活性分子以及成纤维细胞,微血管,免疫系统等其它细胞形态。细胞微环境的组成也处于动态的平衡当中。细胞与细胞微环境的相互作用在组织发育以及疾病发生过程当中起到至关重要的作用。本课题组将主要以乳腺癌作为模型,利用生物化学,细胞生物学的手段以及小鼠模型研究在肿瘤发生及转移过程中癌症细胞与细胞微环境的相互作用,并着重研究:
1) 癌细胞对细胞微环境的调节。特别是成纤维细胞向癌症耦联成纤维细胞/活性成纤维细胞(cancer-associated fibroblasts, CAFs;reactive fibroblasts)的转化。
2) 癌症耦联的细胞微环境诱导上皮细胞的恶性转化。
3) 癌细胞对细胞微环境的入侵及肿瘤的转移。


代表性论文:

  1. Cheng T, Liu Q, Zhang R, Zhang Y, Chen J, Yu R, Ge G#. (2014) Lysyl oxidase promotes bleomycin-induced lung fibrosis through modulating inflammation. J Mol Cell Biol. Epub ahead of print.
  2. Chen C, Wang X, Xiong X, Liu Q, Huang Y, Xu W, Hu J, Ge G, Ling K. (2014) Targeting Type Iγ phosphatidylinositol phosphate kinase inhibits breast cancer metastasis. Oncogene. In press.
  3. Jiang Y, Zhao X, Xiao Q, Liu Q, Ding K, Yu F, Zhang R, Zhu T, Ge G#. (2014) Snail and Slug mediate tamoxifen resistance in breast cancer cells through activation of EGFR-ERK independent of epithelial-mesenchymal transition. J Mol Cell Biol. 6, 352-4.
  4. Han X, Li F, Fang Z, Gao Y, Li F, Fang R, Yao S, Sun Y, Li L, Zhang W, Ma H, Xiao Q, Ge G, Fang J, Wang H, Zhang L, Wong KK, Chen H, Hou Y, Ji H. (2014) Transdifferentiation of lung adenocarcinoma in mice with Lkb1 deficiency to squamous cell carcinoma. Nat Commun. 5, 3261
  5. Xiao Q, and Ge G#. (2012) Lysyl Oxidase, Extracellular Matrix Remodeling and Cancer Metastasis. Cancer Microenviron. 5, 261-73
  6. Xiao G, Deng A, Liu H, Ge G, and Liu, X. (2012) Activator protein 1 suppresses antitumor T-cell function via the induction of programmed death 1. Proc Natl Acad Sci U S A. 109, 15419-24
  7. Sun H, Wu Y, Qi J, Pan Y, Ge G, and Chen J. (2011) The CC’ and DE loops in Ig domains 1 and 2 of MAdCAM-1 play different roles in MAdCAM-1 binding to low- and high-affinity integrin α4β7. J Biol Chem. 286, 12086-12092
  8. Gao Y, Ge G, Ji H.(2011) LKB1 in lung cancerigenesis: a serine/threonine kinase as tumor suppressor. Protein Cell. 2, 99-107
  9. Huang G*, Ge G*, Wang D*, Gopalakrishnan B, Butz DH, Colman RJ, Nagy A, Greenspan DS. (2011) α3(V) Collagen is critical for glucose homeostasis in mice due to effects in pancreatic islets and peripheral tissues. J Clin Invest. 121, 769-783
  10. Gao Y, Xiao Q, Ma H, Li L, Liu J, Feng Y, Fang Z, Wu J, Han X, Zhang J, Sun Y, Wu G, Padera R, Chen H, Wong KK, Ge G#, Ji H#. (2010) LKB1 inhibits lung cancer progression through lysyl oxidase and extracellular matrix remodeling. Proc Natl Acad Sci U S A. 107:18892-7
  11. Huang G, Zhang Y, Kim B, Ge G, Annis DS, Mosher DF, Greenspan DS. (2009) Fibronectin binds and enhances the activity of bone morphogenetic protein 1. J Biol Chem. 284(38):25879-88
  12. Kobayashi K, Luo M, Zhang Y, Wilkes DC, Ge G, Grieskamp T, Yamada C, Liu TC, Huang G, Basson CT, Kispert A, Greenspan DS, Sato TN. (2009) Secreted Frizzled-related protein 2 is a procollagen C proteinase enhancer with a role in fibrosis associated with myocardial infarction. Nat Cell Biol. 11(1):46-55.
  13. Le Goff C, Morice-Picard F, Dagoneau N, Wang LW, Perrot C, Crow YJ, Bauer F, Flori E, Prost-Squarcioni C, Krakow D, Ge G, Greenspan DS, Bonnet D, Le Merrer M, Munnich A, Apte SS, Cormier-Daire V. (2008) ADAMTSL2 mutations in geleophysic dysplasia demonstrate a role for ADAMTS-like proteins in TGF-beta bioavailability regulation. Nat Genet. 40(9):1119-23.
  14. Song W, Wu J, Ge G, Lin Q. (2008) Two domains of the epidermal growth factor receptor are involved in cytoskeletal interactions. Biochem Biophys Res Commun. 370(4):589-93.
  15. Ge G, Fernández CA, Moses, MA and Greenspan DS. (2007) Bone Morphogenetic Protein 1 Processes Prolactin to a 17kDa Anti-Angiogenic Form. Proc Natl Acad Sci U S A. 104(24):10010-5.
  16. Jasuja R, Ge G, Voss N, Lyman-Gingerich J, Branam AB, Pelegri F and Greenspan DS. (2007) Bone Morphogenetic Protein 1 Prodomain Specifically Binds, Localizes and Regulates Signaling of Bone Morphogenetic Proteins 2 and 4. J Biol Chem, 282(12):9053-62.
  17. Zhang Y*, Ge G* and Greenspan DS. (2006) Inhibition of bone morphogenetic protein 1 by native and altered forms of α2-macroglobulin. J Biol Chem, 281: 39096-39104.
  18. Ge G and Greenspan DS. (2006) BMP1 controls TGFβ1 activation via cleavage of latent TGFβ-binding protein. J Cell Biol, 175(1):111-120.
  19. Jasuja R, Voss N, Ge G, Hoffman GG, Lyman-Gingerich J, Pelegri F and Greenspan DS. (2006) bmp1 and mini fin are functionally redundant in regulating formation of the zebrafish dorsoventral axis. Mech Dev, 123:548-558.
  20. Wang WM, Ge G, Lim NH, Nagase H and Greenspan DS. (2006) TIMP-3 inhibits the procollagen N-proteinase ADAMTS-2.Biochem J, 398:515-519.
  21. Ge G and Greenspan DS. (2006) Developmental roles of the BMP1/TLD metalloproteinases. Birth Defects Res C Embryo Today, 78:47-68. (Invited Review)
  22. Ge G, Zhang Y, Steiglitz BM and Greenspan DS. (2006) Mammalian tolloid-like 1 binds procollagen C-proteinase enhancer protein 1 and differs from bone morphogenetic protein 1 in the functional roles of homologous protein domains. J Biol Chem, 281:10786-10798.
  23. Ge G, Hopkins DR, Ho WB and Greenspan DS. (2005) GDF11 forms a bone morphogenetic protein 1-activated latent complex that can modulate nerve growth factor-induced differentiation of PC12 cells. Mol Cell Biol, 25:5846-5858.
  24. Ge G*, Seo NS*, Liang X, Hopkins DR, Hook M and Greenspan DS. (2004) Bone morphogenetic protein-1/tolloid-related metalloproteinases process osteoglycin and enhance its ability to regulate collagen fibrillogenesis. J Biol Chem, 279:41626-41633.
    * Equal contribution
    # Corresponding author
 
   
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