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StroMaP SIGNED

Stromal stress networks underlying phenotypic plasticity and tumor fitness

Total Cost €

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EC-Contrib. €

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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.

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

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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