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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.

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

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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