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StroMaP SIGNED

Stromal stress networks underlying phenotypic plasticity and tumor fitness

Total Cost €

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EC-Contrib. €

0

Partnership

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 StroMaP project word cloud

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

multiplexed    hsf1    co    cancer    transcriptional    outcome    diversity    map    plasticity    tfs    tissue    valuable    implicated    despite    single    tumors    malignancies    reprogrammed    network    stroma    lack    stable    rewiring    genomically    rewired    cell    microenvironment    massive    patient    evolve    phenotypic    vital    evolution    heterogeneously    biology    reprogramming    global    overarching    landscape    intervention    patients    epigenetic    mice    leads    generally    space    context    cycles    discovered    malignancy    orchestrated    mouse    shock    hypothesis    immunofluorescence    models    treatments    genetic    sequencing    hypothesize    nodes    patterns    view    heterogeneity    cells    tumor    cultures    stress    progression    hoemostasis    discover    signatures    theory    adapt    player    transcription    disease    cytoprotective    tme    actionable    first    resolution    aggressiveness    tradeoffs    time    evolutionary    heat    interrogate    activation    malignant    aggressive    rna    complement    ways    tf    contribution    diverse    me   

Project "StroMaP" data sheet

The following table provides information about the project.

Coordinator
WEIZMANN INSTITUTE OF SCIENCE 

Organization address
address: HERZL STREET 234
city: REHOVOT
postcode: 7610001
website: www.weizmann.ac.il

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 Israel [IL]
 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-2017-STG
 Funding Scheme ERC-STG
 Starting year 2017
 Duration (year-month-day) from 2017-10-01   to  2022-09-30

 Partnership

Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 
1    WEIZMANN INSTITUTE OF SCIENCE IL (REHOVOT) coordinator 1˙499˙990.00

Map

 Project objective

The contribution of genetic and epigenetic changes to rewiring of cancer cells into their malignant state has been much studied. But tumors are more than cancer cells and the tumor microenvironment (TME) is a key player in tumor progression. We lack an overarching view of how, despite being genomically stable, the TME is heterogeneously reprogrammed across time and space to promote evolution of aggressive disease. Recently I discovered that Heat-Shock Factor 1 (HSF1), a cytoprotective transcription factor (TF), is vital to this reprogramming, promoting malignancy in patients and mice upon activation in the stroma. Other stress TFs have also been implicated. This leads me to hypothesize that stress responses help tumors adapt and evolve into aggressive malignancies, by enabling heterogeneity and phenotypic diversity in the TME. This plasticity is achieved through cycles of massive transcriptional rewiring orchestrated by a network of stress TFs. To test this hypothesis in a global way we will proceed in three aims. First we will define patterns of stress response activation in the TME by multiplexed immunofluorescence of patient tumors. Then, we will map the associated transcriptional landscape in patients by RNA-sequencing down to single cell resolution and interrogate it in the context of a novel theory of evolutionary tradeoffs so as to discover signatures that promote tumor aggressiveness. Next, we will identify actionable nodes for intervention and test them in cell co-cultures and mouse models. The expected outcome of the proposed research is a detailed network of stress responses that can explain how the TME is rewired in tumors and how variable this rewiring is. This knowledge will provide new ways to target the TME in order to complement treatments focused on cancer cells. More generally, we address key aspects of stress responses, tissue plasticity, hoemostasis and evolution that are expected to be valuable across diverse fields of biology.

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