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首頁 全所PI名錄
  • 葛高翔
  • 研究員，研究組長，博士生導(dǎo)師
  • E-mail: gxge@@sibcb.ac.cn
  • 實驗室主頁: 
    個人簡介：

  • 　　1992年-1996年南京大學(xué)生物化學(xué)系，理學(xué)學(xué)士;1996年-2001年中國科學(xué)院上海生物化學(xué)研究所，理學(xué)博士;2001年-2002年University of Tennessee Health Science Center，博士后;2002年-2007年University of Wisconsin-Madison，先后為博士后，Scientist;2007年起任中國科學(xué)院上海生物化學(xué)與細(xì)胞生物學(xué)研究所研究員，研究組長。

    社會任職：
  •  
    研究方向：
  • 細(xì)胞微環(huán)境對腫瘤發(fā)生及轉(zhuǎn)移的調(diào)控
    研究工作：

  • 　　細(xì)胞對外界刺激的反應(yīng)不僅取決于細(xì)胞本身特性，同時也受到細(xì)胞微環(huán)境(microenvironment)的調(diào)節(jié)。以上皮細(xì)胞為例，其細(xì)胞微環(huán)境包括細(xì)胞外基質(zhì)(Extracellular Matrix, ECM)，生長因子/激素，蛋白酶等活性分子以及成纖維細(xì)胞，微血管，免疫系統(tǒng)等其它細(xì)胞形態(tài)。細(xì)胞微環(huán)境的組成也處于動態(tài)的平衡當(dāng)中。細(xì)胞與細(xì)胞微環(huán)境的相互作用在組織發(fā)育以及疾病發(fā)生過程當(dāng)中起到至關(guān)重要的作用。本課題組將主要以乳腺癌作為模型，利用生物化學(xué)，細(xì)胞生物學(xué)的手段以及小鼠模型研究在腫瘤發(fā)生及轉(zhuǎn)移過程中癌癥細(xì)胞與細(xì)胞微環(huán)境的相互作用，并著重研究：

    　　1) 癌細(xì)胞對細(xì)胞微環(huán)境的調(diào)節(jié)。特別是成纖維細(xì)胞向癌癥耦聯(lián)成纖維細(xì)胞/活性成纖維細(xì)胞(cancer-associated fibroblasts, CAFs;reactive fibroblasts)的轉(zhuǎn)化。

    　　2) 癌癥耦聯(lián)的細(xì)胞微環(huán)境誘導(dǎo)上皮細(xì)胞的惡性轉(zhuǎn)化。

    　　3) 癌細(xì)胞對細(xì)胞微環(huán)境的入侵及腫瘤的轉(zhuǎn)移。

    承擔(dān)科研項目情況：
    代表論著：
    1. Zhang R#, Gao Y#, Zhao X#, Gao M#, Wu Y, Han Y, Qiao Y, Luo Z, Yang L, Chen J, and Ge G*. (2018) FSP1-positive fibroblasts are adipogenic niche and regulate adipose homeostasis. PLOS Biol. 16(8): e2001493
    2. Wang S, Wu C, Zhang Y, Zhong Q, Sun H, Cao W, Ge G, Li G*, Zhang XF*, and Chen J*. (2018) Integrin α4β7 switches its ligand specificity via distinct conformer-specific activation.J Cell Biol. [Epub ahead of print]
    3. Zhang R#, Ma H#, Gao Y#, Wu Y, Qiao Y, Geng A, Cai C, Han Y, Zeng YA, Liu X*, and Ge G*. (2018) Th-POK regulates mammary gland lactation through mTOR-SREBP pathway. PLoS Genet. 14(2):e1007211. doi:10.1371/journal.pgen.1007211.
    4. Gao Y, Wu Y, Han Y, and Ge G*. (2017) Extracellular Matrix and Cancer-associated Fibroblasts. Progr Biochem Biophy. 44(8): 660~671
    5. Huang G, Ge G, Izzi V, and Greenspan DS*. (2017) a3(V) collagen regulates breast tumor growth via glypican-1. Nat Commun. 8:14351. doi: 10.1038/ncomms14351.
    6. Xiao Q, Jiang Y, Liu Q, Yue J, Liu C, Zhao X, Qiao Y, Ji H, Chen J and Ge G*. (2015) Minor type IV collagen a5 chain promotes cancer progression through discoidin domain receptor-1. PLOS Genet, 11(5): e1005249. doi:10.1371/journal.pgen.1005249
    7. Xia P, Zhang R and Ge G*. (2015) C/EBPβ mediates TNF-α-induced cancer cell migration by inducing MMP expression dependent on p38 MAPK. J Cell Biochem, 116(12):2766-77.
    8. Chen C#, Wang X#, Xiong X#, Liu Q, Huang Y, Xu W, Hu J, Ge G, Ling K*. (2015) Targeting Type Iγ phosphatidylinositol phosphate kinase inhibits breast cancer metastasis. Oncogene. 34(35):4635-46.
    9. Cheng T#, Liu Q#, Zhang R, Zhang Y, Chen J, Yu R, and Ge G*. (2014) Lysyl oxidase promotes bleomycin-induced lung fibrosis through modulating inflammation. J Mol Cell Biol. 6(6):506-15.
    10. Jiang Y#, Zhao X#, Xiao Q, Liu Q, Ding K, Yu F, Zhang R, Zhu T, and 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.
    11. 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
    12. Xiao Q, and Ge G*. (2012) Lysyl Oxidase, Extracellular Matrix Remodeling and Cancer Metastasis. Cancer Microenviron. 5, 261-73
    13. 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
    14. Ma HM, and Ge G*. (2012) Desmoplasia and cancer. Chin J Cell Biol. 34(7): 635-44.
    15. 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 a4b7. J Biol Chem. 286, 12086-12092
    16. Gao Y, Ge G*, Ji H*.(2011) LKB1 in lung cancerigenesis: a serine/threonine kinase as tumor suppressor. Protein Cell. 2, 99-107
    17. 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
    18. 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
    19. 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
    20. 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.
    21. 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.
    22. 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.
    23. 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.
    24. 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.
    25. 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.
    26. Ge G and Greenspan DS*. (2006) BMP1 controls TGFβ1 activation via cleavage of latent TGFβ-binding protein. J Cell Biol, 175(1):111-120.
    27. 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.
    28. 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.
    29. Ge G and Greenspan DS*. (2006) Developmental roles of the BMP1/TLD metalloproteinases. Birth Defects Res C Embryo Today, 78:47-68. (Invited Review)
    30. 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.
    31. 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.
    32. 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.
    33. Ge G, Wu, J, Wang Y and Lin QS*. (2002) Activation mechanism of solubilized epidermal growth factor tyrosine kinase. Biochem Biophys Res Commun, 290:914-20.
    34. Ge G#, Wu J# and Lin QS*. (2001) Effect of membrane fluidity on tyrosine kinase activity of reconstituted Epidermal Growth Factor Receptor. Biochem Biophys Res Commun, 282:511-514.
    35. Ge G, Wu J and Lin QS*. (2001) Non-radioisotopic method for the in vitro measurement of EGF receptor tyrosine kinase. Chinese Science Bulletin, 46:683-685.
    獲獎及榮譽：
    研究組成員：