Lymphangiogenomics

 

 
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Specification of endothelial identity and identification of novel lymphangiogenic genes

 

 

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Last Update: June 23, 2009

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

  

 

 

 

  

 

 

 

 

Our work aims at defining conditions for the isolation, expansion, and induction of differentiation of EPCs. The work focuses on the identification of genes specifically expressed at early stages of endothelial differentiation and definition of the EPC phenotype. Transcription factors and other relevant genes associated with endothelial specification will be identified and eventually used to induce and manipulate endothelial differentiation.

 

 

Responsible for this project:

 

 

Dr. Elisabetta Dejana

IFOM Fondazione Istituto FIRC di Oncologia Molecolare

Via Adamello 16

20139 Milan, Italy

Phone: +39 02 574 303 234

Fax: +39 02 574 303 231

E-mail: dejana(at)ifom-firc.it

Homepage: www.semm.it/phd_programme/faculty/dejana.html

 

 

Selected recent publications:

  1. Liebner S, Corada M, Bangsow T, Babbage J, Taddei A, Czupalla CJ, Reis M, Felici A, Wolburg H, Fruttiger M, Taketo MM, von Melchner H, Plate KH, Gerhardt H, Dejana E. Wnt/beta-catenin signaling controls development of the blood-brain barrier. J Cell Biol. 3;183(3):409-17, 2008.
     
  2. Taddei A, Giampietro C, Conti A, Orsenigo F, Breviario F, Pirazzoli V, Potente M, Daly C, Dimmeler S, Dejana E. Endothelial adherens junctions control tight junctions by VE-cadherin-mediated upregulation of claudin-5. Nat Cell Biol. 10(8):923-34, 2008.
     
  3. Rudini N, Felici A, Giampietro C, Lampugnani M, Corada M, Swirsding K, Garrè M, Liebner S, Letarte M, ten Dijke P, Dejana E.VE-cadherin is a critical endothelial regulator of TGF-beta signalling. EMBO J. 27(7):993-1004, 2008.
     
  4. Bazzoni G, Dejana E. Endothelial cell-to-cell junctions: molecular organization and role in vascular homeostasis. Physiol Rev 84:869-901, 2004.
     

  5. Iurlaro M, Demontis F, Corada M, Zanetta L, Drake C, Gariboldi M, Peiro S, Cano A, Navarro P, Cattelino A, Tognin S, Marchisio PC, Dejana E. VE-Cadherin Expression and Clustering Maintain Low Levels of Survivin in Endothelial Cells. Am J Pathol 165:181-189, 2004.
     

  6. Spagnuolo R, Corada M, Orsenigo F, Zanetta L, Deuschle U, Sandy P, Schneider C, Drake CJ, Breviario F, Dejana E. Gas1 is induced by VE-cadherin and vascular endothelial growth factor and inhibits endothelial cell apoptosis. Blood 103:3005-3012, 2004.
     

  7. Cusella De Angelis MG, Balconi G, Bernasconi S, Zanetta L, Boratto R, Galli D, Dejana E, Cossu G. Skeletal myogenic progenitors in the endothelium of lung and yolk sac. Exp Cell Res 290:207-216, 2003.
     

  8. Cattelino A, Liebner S, Gallini R, Zanetti A, Balconi G, Corsi A, Bianco P, Wolburg H, Moore R, Oreda B, Kemler R, Dejana E. The conditional inactivation of the beta-catenin gene in endothelial cells causes a defective vascular pattern and increased vascular fragility. J Cell Biol 162:1111-1122, 2003.
     

  9. Lindblom P, Gerhardt H, Liebner S, Abramsson A, Enge M, Hellstrom M, Backstrom G, Fredriksson S, Landegren U, Nystrom HC, Bergstrom G, Dejana E, Ostman A, Lindahl P, Betsholtz C. Endothelial PDGF-B retention is required for proper investment of pericytes in the microvessel wall. Genes Dev 17:1835-1840, 2003.
     

  10. Grazia Lampugnani M, Zanetti A, Corada M, Takahashi T, Balconi G, Breviario F, Orsenigo F, Cattelino A, Kemler R, Daniel TO, Dejana E. Contact inhibition of VEGF-induced proliferation requires vascular endothelial cadherin, beta-catenin, and the phosphatase DEP-1/CD148. J Cell Biol 161:793-804, 2003.
     

  11. Corada M, Zanetta L, Orsenigo F, Breviario F, Lampugnani MG, Bernasconi S, Liao F, Hicklin DJ, Bohlen P, Dejana E. A monoclonal antibody to vascular endothelial-cadherin inhibits tumor angiogenesis without side effects on endothelial permeability. Blood 100:905-911, 2002.
     

  12. Shay-Salit A, Shushy M, Wolfovitz E, Yahav H, Breviario F, Dejana E, Resnick N. VEGF receptor 2 and the adherens junction as a mechanical transducer in vascular endothelial cells. Proc Natl Acad Sci USA 99:9462-9467, 2002.
     

  13. Liao F, Doody JF, Overholser J, Finnerty B, Bassi R, Wu Y, Dejana E, Kussie P, Bohlen P, Hicklin DJ. Selective targeting of angiogenic tumor vasculature by vascular endothelial-cadherin antibody inhibits tumor growth without affecting vascular permeability. Cancer Res 62:2567-2575, 2002.
     

  14. Lampugnani MG, Zanetti A, Breviario F, Balconi G, Orsenigo F, Corada M, Spagnuolo R, Betson M, Braga V, Dejana E. VE-cadherin regulates endothelial actin activating Rac and increasing membrane association of Tiam. Mol Biol Cell 13:1175-1189, 2002.
     

  15. Zanetti A, Lampugnani MG, Balconi G, Breviario F, Corada M, Lanfrancone L, Dejana E. Vascular endothelial growth factor induces SHC association with vascular endothelial cadherin: a potential feedback mechanism to control vascular endothelial growth factor receptor-2 signaling. Arterioscler Thromb Vasc Biol 22:617-622, 2002.
     

  16. Bussolino F, Serini G, Mitola S, Bazzoni G, Dejana E. Dynamic modules and heterogeneity of function: a lesson from tyrosine kinase receptors in endothelial cells. EMBO Rep 2:763-767, 2001.
     

  17. Condorelli G, Borello U, De Angelis L, Latronico M, Sirabella D, Coletta M, Galli R, Balconi G, Follenzi A, Frati G, Cusella De Angelis MG, Gioglio L, Amuchastegui S, Adorini L, Naldini L, Vescovi A, Dejana E, Cossu G. Cardiomyocytes induce endothelial cells to trans-differentiate into cardiac muscle: implications for myocardium regeneration. Proc Natl Acad Sci USA 98:10733-10738, 2001.
     

  18. Kostrewa D, Brockhaus M, D'Arcy A, Dale GE, Nelboeck P, Schmid G, Mueller F, Bazzoni G, Dejana E, Bartfai T, Winkler FK, Hennig M. X-ray structure of junctional adhesion molecule: structural basis for homophilic adhesion via a novel dimerization motif. EMBO J 20:4391-4398, 2001.
     

  19. Corada M, Liao F, Lindgren M, Lampugnani MG, Breviario F, Frank R, Muller WA, Hicklin DJ, Bohlen P, Dejana E. Monoclonal antibodies directed to different regions of vascular endothelial cadherin extracellular domain affect adhesion and clustering of the protein and modulate endothelial permeability. Blood 97:1679-1684, 2001.
     

Reviews:

  1. Dejana E. Endothelial cell-cell junctions: happy together. Nat Rev Mol Cell Biol 5:261-270, 2004.
     

  2. Bazzoni G, Dejana E. Keratinocyte junctions and the epidermal barrier: how to make a skin-tight dress. J Cell Biol 156:947-949, 2002.
     

  3. Dejana E, Spagnuolo R, Bazzoni G. Interendothelial junctions and their role in the control of angiogenesis, vascular permeability and leukocyte transmigration. Thromb Haemost 86:308-315, 2001.
     

  4. Bazzoni G, Dejana E. Pores in the sieve and channels in the wall: control of paracellular permeability by junctional proteins in endothelial cells. Microcirculation 8:143-152, 2001.