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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

0

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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.

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

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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