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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.

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

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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