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LeukemiaEnviron SIGNED

SIGNALING PROPENSITY IN THE MICROENVIRONMENT OF B CELL CHRONIC LYMPHOCYTIC LEUKEMIA

Total Cost €

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EC-Contrib. €

0

Partnership

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 LeukemiaEnviron project word cloud

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

adults    node    transferable    therapy    constantly    disease    cells    animal    regulation    interactions    interaction    therapeutically    mir    see    therapeutic    circulate    il4    re    peripheral    mediated    mouse    inhibitors    acts    normal    reveal    microenvironmental    function    proliferative    inhibited    leukemia    regulator    mechanisms    blood    malignant    cd20    unknown    responsible    complicates    lymph    signalling    integrate    mirnas    cell    data    interleukin    frequent    rituximab    therapies    biology    figure    implication    utilized    proteins    survival    cll    influences    engraftment    relevance    nodes    12    activation    print    29    pro    signals    led    samples    hypothesize    immune    first    finger    receptor    pdx    course    times    proliferation    primary    propensity    dependency    universal    signaling    malignancies    vs    transplantable    bcr    lymphocytic    cd40    microenvironment    obtain    microenvironments    niches    model    stable    stream    chronic    nfkb   

Project "LeukemiaEnviron" data sheet

The following table provides information about the project.

Coordinator
Masarykova univerzita 

Organization address
address: Zerotinovo namesti 9
city: BRNO STRED
postcode: 60177
website: http://www.muni.cz

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 Czech Republic [CZ]
 Total cost 1˙499˙990 €
 EC max contribution 1˙499˙990 € (100%)
 Programme 1. H2020-EU.1.1. (EXCELLENT SCIENCE - European Research Council (ERC))
 Code Call ERC-2018-STG
 Funding Scheme ERC-STG
 Starting year 2019
 Duration (year-month-day) from 2019-06-01   to  2024-05-31

 Partnership

Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 
1    Masarykova univerzita CZ (BRNO STRED) coordinator 1˙499˙990.00

Map

 Project objective

B cell chronic lymphocytic leukemia (CLL) is the most frequent leukemia in adults. CLL cells are characterized by their universal dependency on pro-survival and pro-proliferative signals from immune niches. To achieve this they constantly re-circulate between blood and lymph nodes, which is inhibited by novel microenvironment-targeting therapies such as “BCR inhibitors”. We aim to reveal how the malignant B cells change the propensity of their signalling pathways in response to the different microenvironments such as peripheral blood vs lymph node to obtain the proliferative signals. This is of major relevance for CLL, but also transferable to the biology of some other B cell malignancies and/or normal B cells. We analyzed the “finger print” of microenvironmental interactions in many CLL samples at various times during the disease course or during therapy. The obtained data led us to hypothesize on the mechanisms of regulation of signalling propensity of two pathways that are responsible for proliferation and survival of CLL cells, namely B Cell Receptor (BCR) signalling and signals from T-cells mediated by CD40/IL4. In aim 1 we hypothesize that CD20 is one of the key proteins involved in CLL cell activation, and influences BCR and interleukin signalling (see figure). This has important therapeutic implication since CD20 is used as a therapeutic target for 20 years (rituximab), but its function in CLL/normal B cells is unknown. In aim 2 we hypothesize that miR-29 acts a key regulator of T-cell signalling from CD40 and down-stream NFkB activation (see figure). This represents the first example of miRNAs‘ role in the propensity of T-cell interaction, and could be also utilized therapeutically. In aim 3 we will integrate our data on microenvironmental signaling (aim 12) and develop a first mouse model for PDX that would allow stable engraftment of primary CLL cells. Currently, CLL is non-transplantable to any animal model which complicates studies of its biology.

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

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