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Faculty

Members of CAS, CAE
National Outstanding Young Scientists Award
Principal Investigators
Address: 320 Yue Yang Road, Shanghai 200031, P.R. China
Tel: 86-21-54920000
Fax: 86-21-54921011
Email: sibcb@sibs.ac.cn
Website: www.sibcb.ac.cn
Principal Investigators
GE Gaoxiang
Ph.D., Professor
Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 320 Yue-yang Road, Shanghai 200031, China.
Email: gxge@@sibcb.ac.cn

Research Areas
microenvironment; extracellular matrix (ECM); cancer-associated fibroblasts (CAFs); malignant transformation; metastasis; metalloproteinase

Research Interests
Microenvironments of cells, via cell-cell contact, cell-extracellular matrix (ECM) interaction and growth factors, retain the characteristics of cells, as well as their response to stimuli. The importance of microenvironment in pathogenesis is becoming much more recognized, from the role of ECM and matrix density in determining polarity and growth potential of tissues, to the extracellular metabolism of growth factors and matrix molecules during inflammation and cancer. The long-term objective of Ge laboratory is to understand the cross-talk between cells and microenvironment during morphogenesis and homeostasis. Much attention will be paid to pathological conditions, where disordered microenvironment and abnormal cell behavior have occurred. Cancer is the No. 2 killer worldwide. Despite much efforts, tumor progression and metastasis remain largely mysterious, which unfortunately retards the invention of effective therapeutic strategies and medicine. Accompanying growth of tumor cells, local microenvironment undergoes dynamic morphological and molecular changes, which further facilitate uncontrolled growth of tumor cells. The global and systematic impact of tumor cells is reflected by the fact that tumor cells induce the establishment of pre-metastatic niche in distant organs. The communication between tumor cells and foreign microenvironment in distant organs leads to ultimate organ-specific metastasis. Ge laboratory studies the interaction of tumor cells and microenvironment in breast cancer onset, progression and metastasis, by utilizing breast cancer model mice, as well as approaches of biochemistry, molecular biology and cell biology. The work in Ge laboratory focuses on 1) Dynamic remodeling of ECM during breast cancer progression; 2) Differential responses of cells to microenvironment with varied ECM protein composition and organization, as well as availability/ activity of growth factors; 3) Conversion of resting, normal fibroblasts to reactive, cancer- associated fibroblasts (CAFs); 4) Communication between breast cancer cells and CAFs; 5) Dynamic changes of microenvironment during metastasis and organ-specific metastasis.

Selected Publications

  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 47 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/EBP mediates TNF--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 I 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) 3(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, Fernndez 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 2-macroglobulin. J Biol Chem, 281: 39096-39104.
  26. Ge G and Greenspan DS*. (2006) BMP1 controls TGF1 activation via cleavage of latent TGF-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.

Education Background & Academic Experience
1992-1996       B.S., Department of Biochemistry, Nanjing University
1996-2001       Ph.D., Shanghai Institute of Biochemistry, Chinese Academy of Sciences
2001-2002       Postdoctoral fellowDepartment of Pharmacology, University of Tennessee Health Science Center
2002-2007       Research Associate, Scientist, Department of Pathology and Laboratory Medicine, University of Wisconsin- Madison

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