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MSCFate

Fate of mammary stem cells during tumorigenesis and clinical implications

Total Cost €

0

EC-Contrib. €

0

Partnership

0

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 MSCFate project word cloud

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

msc    investigation    resistance    cancer    cells    differentiation    pi3k    biomarkers    acquires    catalytic    standard    occurs    phosphoinositide    responsible    coding    perturbation    molecular    inhibitors    oncogenic    conditional    pik3ca    phenotype    reduces    kinase    mutations    gene    perturb    genetic    subunit    portrait    vivo    biology    poorly    therapies    ing    tracing    fate    e545k    preclinical    pinpoint    ultimately    mouse    cell    one    questions    elucidate    progression    found    lineage    trigger    hyperactive    events    shown    combination    tumor    suggests    heterogeneity    drug    mammary    procr    h1047r    unbiased    clinical    regulates    consequently    explored    knew    origin    promotion    hypothesis    proliferation    first    transformation    metastasis    model    chemotherapy    patients    accumulating    hotspot    generate    stem    panel    models    initiate    tissue    tumors    situ    event    mechanisms    expression    homeostasis    eventual    therapy    reports    contribution    breast    hypothesize   

Project "MSCFate" data sheet

The following table provides information about the project.

Coordinator
UNIVERSITAT BASEL 

Organization address
address: PETERSPLATZ 1
city: BASEL
postcode: 4051
website: www.unibas.ch

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 Switzerland [CH]
 Project website https://bentireslab.org/
 Total cost 175˙419 €
 EC max contribution 175˙419 € (100%)
 Programme 1. H2020-EU.1.3.2. (Nurturing excellence by means of cross-border and cross-sector mobility)
 Code Call H2020-MSCA-IF-2016
 Funding Scheme MSCA-IF-EF-ST
 Starting year 2017
 Duration (year-month-day) from 2017-09-01   to  2019-08-31

 Partnership

Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 
1    UNIVERSITAT BASEL CH (BASEL) coordinator 175˙419.00

Map

 Project objective

One of the most challenging questions in breast cancer biology is to elucidate the origin of tumor heterogeneity and its contribution to therapy failure. Accumulating evidence suggests that the cell-of-origin, the cell that acquires the first oncogenic event, may define the molecular portrait of the resulting tumor. The fate of mammary Stem Cells (MSC) upon oncogenic perturbation has been poorly explored. Moreover, the Phosphoinositide 3-kinase (PI3K) pathway regulates proliferation/differentiation of MSC and is found hyperactive in breast cancer cells, for example through mutations in PIK3CA, the gene coding for its catalytic subunit. I hypothesize that expression of PIK3CA mutations will perturb mammary tissue homeostasis, initiate mammary cancer and trigger formation of stem-like cancer cells. Using state-of-the-art in situ genetic lineage tracing, I will determine the fate of MSC (identified recently as Procr cells) after conditional expression of PIK3CA hotspot mutations (H1047R, E545K). I will also characterize early molecular events responsible for promotion of transformation (Aim 1). When tumors develop, I will determine tumor phenotype and eventual progression to metastasis (Aim 2). Consequently, this study will generate a new mouse model of breast cancer that will be useful for preclinical studies. A panel of PI3K inhibitors is currently under Clinical investigation and clinical reports have shown that the combination of standard chemotherapy with PI3K inhibitors reduces tumor growth but drug-resistance often occurs. To identify resistance mechanisms to PI3K inhibitors, I will generate in vivo models of drug-resistance (Aim 3). My studies will use both hypothesis driven and unbiased approaches, they should: 1. better elucidate transformation of MSC and the resulting tumor heterogeneity, 2. pinpoint novel targets/biomarkers. Ultimately this knew knowledge should result in better therapies for patients.

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The information about "MSCFATE" are provided by the European Opendata Portal: CORDIS opendata.

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