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V-EPC SIGNED

Inherited disfunctions of brain microcirculation

Total Cost €

0

EC-Contrib. €

0

Partnership

0

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 V-EPC project word cloud

Explore the words cloud of the V-EPC project. It provides you a very rough idea of what is the project "V-EPC" about.

expression    skull    medical    expansion    epcs    vessels    anyone    cells    clonal    reminiscent    missing    capacity    epc    vascular    mesenchymal    function    initiating    possibility    differentially    treatments    familial    introduce    co    expressing    functions    resident    proliferation    proliferative    prevent    preliminary    cavernous    paralysis    reduce    hypothesis    angiogenic    venous    express    isolated    originates    focal    tools    stimuli    hemorrhages    maturation    genetic    located    nervous    endothelial    gene    divided    undergoing    cell    malformations    ecs    bleed    ccm1    mouse    genes    combined    profile    disease    lining    mutation    normal    ccm    endothelium    nature    therapy    human    selective    markers    intermingled    mature    tumor    form    signaling    capillary    mutations    vivo    specimens    cerebral    patients    surgery    trigger    stem    population    successful    identification    biology    models    rare    therapeutic    inducing    cavernomas    sensitive    observation    seizures    fragile    pharmacological    central    inactivation   

Project "V-EPC" data sheet

The following table provides information about the project.

Coordinator
IFOM FONDAZIONE ISTITUTO FIRC DI ONCOLOGIA MOLECOLARE 

Organization address
address: VIA ADAMELLO 16
city: MILANO
postcode: 20139
website: www.ifom-firc.it

contact info
title: n.a.
name: n.a.
surname: n.a.
function: n.a.
email: n.a.
telephone: n.a.
fax: n.a.

 Coordinator Country Italy [IT]
 Total cost 2˙451˙250 €
 EC max contribution 2˙451˙250 € (100%)
 Programme 1. H2020-EU.1.1. (EXCELLENT SCIENCE - European Research Council (ERC))
 Code Call ERC-2016-ADG
 Funding Scheme ERC-ADG
 Starting year 2017
 Duration (year-month-day) from 2017-09-01   to  2022-08-31

 Partnership

Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 
1    IFOM FONDAZIONE ISTITUTO FIRC DI ONCOLOGIA MOLECOLARE IT (MILANO) coordinator 2˙451˙250.00

Map

 Project objective

Cerebral cavernous malformations (CCM) is a disease characterized by focal capillary-venous cavernomas located in the central nervous system. These malformations are fragile and bleed leading to seizures, paralysis and cerebral hemorrhages. The familial form of CCM is due to loss of function mutations of anyone of three genes called Ccm1, Ccm 2 and Ccm 3. Open skull surgery is the only possible therapy since effective medical treatments are still missing. In mouse models of CCM and human patients’ specimens, endothelial cells (ECs) lining the cavernomas co-express endothelial, mesenchymal and stem cell markers. These features combined to high cell proliferation are reminiscent of tumor initiating cells. In preliminary work, we isolated a rare population of highly proliferative ECs (V-EPC) intermingled with the normal vascular endothelium in vivo and co-expressing endothelial and stem cell markers. Our working hypothesis is that CCM originates from the clonal expansion of these V-EPCs that are more sensitive than mature endothelium to inactivation of Ccm genes. This possibility is supported by the observation that V-EPCs present a comparable gene expression profile and selective markers than the ECs lining CCM cavernomas. The project is divided in three related objectives: 1) To define the nature and functions of V-EPCs in normal vessels; 2) to test the capacity of V-EPCs to trigger the formation of CCM by undergoing clonal expansion in vivo; 3) to test whether targeting V-EPCs or inducing V-EPC maturation by pharmacological tools reduce or prevent the formation of CCM. If successful this work will introduce novel concepts in vascular biology such as: 1) the presence of resident V-EPCs that are differentially sensitive than mature endothelium to the same genetic mutation and angiogenic stimuli; 2) the identification of specific signaling pathways in V-EPC that explain their high proliferative potential; 3) the identification of V-EPC as therapeutic targets for CCM.

 Publications

year authors and title journal last update
List of publications.
2019 Monica Corada, Fabrizio Orsenigo, Ganesh Parameshwar Bhat, Lei Liu Conze, Ferruccio Breviario, Sara Isabel Cunha, Lena Claesson-Welsh, Galina V. Beznoussenko, Alexander A. Mironov, Marco Bacigaluppi, Gianvito Martino, Mara E. Pitulescu, Ralf H. Adams, Peetra Magnusson, Elisabetta Dejana
Fine-Tuning of Sox17 and Canonical Wnt Coordinates the Permeability Properties of the Blood-Brain Barrier
published pages: 511-525, ISSN: 0009-7330, DOI: 10.1161/circresaha.118.313316
Circulation Research 124/4 2019-10-29
2018 Marco F. Morini, Costanza Giampietro, Monica Corada, Federica Pisati, Elisa Lavarone, Sara I. Cunha, Lei L. Conze, Nicola O’Reilly, Dhira Joshi, Svend Kjaer, Roger George, Emma Nye, Anqi Ma, Jian Jin, Richard Mitter, Michela Lupia, Ugo Cavallaro, Diego Pasini, Dinis P. Calado, Elisabetta Dejana, Andrea Taddei
VE-Cadherin–Mediated Epigenetic Regulation of Endothelial Gene Expression
published pages: 231-245, ISSN: 0009-7330, DOI: 10.1161/circresaha.117.312392
Circulation Research 122/2 2019-10-08
2017 Sara I. Cunha, Peetra U. Magnusson, Elisabetta Dejana, Maria Grazia Lampugnani
Deregulated TGF-β/BMP Signaling in Vascular Malformations
published pages: 981-999, ISSN: 0009-7330, DOI: 10.1161/circresaha.117.309930
Circulation Research 121/8 2019-10-08
2018 Elisabetta Dejana, Maria Grazia Lampugnani
Endothelial cell transitions
published pages: 746-747, ISSN: 0036-8075, DOI: 10.1126/science.aas9432
Science 362/6416 2019-10-08

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