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PhaseControl SIGNED

How cellular suicide programmes control phase transitions in fatty liver disease and liver cancer

Total Cost €

0

EC-Contrib. €

0

Partnership

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 PhaseControl project word cloud

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

patients    hepatocarcinogenesis    stage    risk    exploring    healthy    relevance    human    hepatocellular    warning    transition    unexpected    apoptosis    functions    functionally    independent    driver    myeloid    form    hepatocytes    networks    serves    death    systematic    inflammatory    examine    mlkl    signs    explore    nash    mutations    white    alcoholic    interact    mediate    adipose    road    made    tissue    metabolic    regulation    regulate    progression    fundamental    phasecontrol    wat    breaking    necroptosis    reactivity    definition    discovered    prevention    chemoprevention    ground    decompensation    chronic    critical    transitions    alterations    innovative    drivers    stable    modulate    molecular    carcinoma    undergoes    disease    regulatory    organ    molecules    hcc    solid    dependent    cells    ripk3    diseases    cohort    liver    genetic    indicating    programmed    inflammation    steatohepatitis    phases    mediators    cell    initially    murine    prediction    newly    model    cancer    demonstrating   

Project "PhaseControl" data sheet

The following table provides information about the project.

Coordinator
UNIVERSITAETSKLINIKUM AACHEN 

Organization address
address: Pauwelsstrasse 30
city: AACHEN
postcode: 52074
website: www.ukaachen.de

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 Germany [DE]
 Total cost 1˙997˙840 €
 EC max contribution 1˙997˙840 € (100%)
 Programme 1. H2020-EU.1.1. (EXCELLENT SCIENCE - European Research Council (ERC))
 Code Call ERC-2017-COG
 Funding Scheme ERC-COG
 Starting year 2018
 Duration (year-month-day) from 2018-11-01   to  2023-10-31

 Partnership

Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 
1    UNIVERSITAETSKLINIKUM AACHEN DE (AACHEN) coordinator 1˙997˙840.00

Map

 Project objective

The progression from a healthy liver towards non-alcoholic steatohepatitis (NASH) and hepatocellular carcinoma (HCC) serves as a model for chronic diseases in a solid organ, demonstrating how an initially stable stage undergoes critical transitions along several defined phases. Defining the molecular drivers of these phase transitions will open the road for the definition of warning signs, risk prediction approaches and prevention of disease decompensation in human liver disease. We recently made several ground-breaking findings indicating that the molecules RIPK3 and MLKL – which regulate a novel form of programmed cell death called necroptosis – are crucial mediators of these phase transitions, but they might have unexpected and cell-death-independent functions. Therefore, PhaseControl aims at exploring the specific functions of these molecules at the critical phase transitions towards NASH/HCC. Specifically, I propose to apply a systematic approach and innovative methods to

1) explore cell-type specific RIPK3- and MLKL-dependent regulatory networks in white adipose tissue (WAT), hepatocytes and myeloid cells in murine NASH development and define cell-death independent functions of MLKL in metabolic regulation; 2) explore how inflammatory pathways in hepatocytes modulate the reactivity and specific responses towards necroptosis at the transition towards hepatocellular carcinoma (HCC); 3) examine apoptosis- and necroptosis-specific genetic alterations and driver mutations that mediate the transition from chronic inflammation to HCC; 4) evaluate in a cohort of human patients if these newly discovered pathways can be used for risk-prediction approaches and might be chemoprevention targets against HCC.

The expected results will establish a novel concept how programmed cell death, inflammation and metabolic pathways functionally interact in hepatocarcinogenesis with fundamental relevance for risk prediction and chemoprevention of human liver cancer.

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

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