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H I C I SIGNED

Transcriptional and epigenetic control of tissue regenerative HB-EGF in autoimmune CNS inflammation

Total Cost €

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EC-Contrib. €

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Partnership

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 H I C I project word cloud

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

hb    sites    monitoring    serum    cerebrospinal    acute    exacerbated    recover    nasal    accumulation    explore    neurological    therapeutically    astrocytes    ahr    dna    egf    animal    protective    mediated    preliminary    inflammation    prevented    biomarkers    chronic    mechanisms    translational    central    epigenetic    progressive    induce    induction    hydrocarbon    sclerosis    promoter    led    tissue    regulation    worsening    stages    diseases    disease    inflammatory    nervous    model    autoimmune    gain    therapy    regeneration    ligand    revealed    knocking    decreased    cns    ms    heparin    regenerative    concomitantly    multiple    methylation    cells    transcription    glial    status    methyltransferase    blockade    therapeutic    unknown    degenerative    aryl    fail    destruction    untreatable    validate    risk    patients    modifications    inhibited    deficits    activation    dnmt1    discovered    fluid    binding    inhibit    ligands    receptor    knock    astrocytic   

Project "H I C I" data sheet

The following table provides information about the project.

Coordinator
KLINIKUM RECHTS DER ISAR DER TECHNISCHEN UNIVERSITAT MUNCHEN 

Organization address
address: ISMANINGER STRASSE 22
city: MUENCHEN
postcode: 81675
website: http://www.med.tu.muenchen.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˙499˙706 €
 EC max contribution 1˙499˙706 € (100%)
 Programme 1. H2020-EU.1.1. (EXCELLENT SCIENCE - European Research Council (ERC))
 Code Call ERC-2019-STG
 Funding Scheme ERC-STG
 Starting year 2020
 Duration (year-month-day) from 2020-03-01   to  2025-02-28

 Partnership

Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 
1    KLINIKUM RECHTS DER ISAR DER TECHNISCHEN UNIVERSITAT MUNCHEN DE (MUENCHEN) coordinator 1˙499˙706.00

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 Project objective

Multiple Sclerosis (MS) is an autoimmune inflammatory disease of the central nervous system (CNS), in which chronic inflammation and failure of regenerative mechanisms lead to progressive tissue destruction and accumulation of neurological deficits. Glial cells such as astrocytes induce regenerative processes in acute inflammation, but fail to inhibit tissue destruction for yet unknown reasons in chronic disease. In preliminary studies, we identified heparin-binding EGF-like growth factor (HB-EGF) in astrocytes as novel tissue protective factor. Indeed, knock-down of HB-EGF in astrocytes led to exacerbated disease and failure to recover in an animal model of MS. Promoter studies revealed induction of HB-EGF by the ligand-induced transcription factor aryl hydrocarbon receptor (AHR) in acute inflammation. However, astrocytic HB-EGF decreased in chronic stages concomitantly with progressive disease worsening. Analyses of AHR binding sites in the HB-EGF promoter revealed epigenetic modifications mediated by DNA-Methyltransferase 1 (DNMT1) in chronic inflammation, which inhibited promoter activation by AHR. Knocking down DNMT1 prevented epigenetic changes and increased HB-EGF production in chronic stages. Thus, we have discovered astrocytic HB-EGF as a novel regenerative factor and its regulation by AHR and DNMT1, which could be targeted therapeutically to enhance tissue regeneration in chronic stages. In this project, we will define the role of HB-EGF in acute and chronic autoimmune CNS inflammation (Aim 1), its regulation by AHR and DNMT1 (Aim 2), and the therapeutic value of nasal HB-EGF application or DNMT1 blockade (Aim 3). In a translational approach, we will validate AHR ligands, HB-EGF and HB-EGF promoter methylation status in serum and cerebrospinal fluid of MS patients as novel biomarkers for MS (Aim 4). These high risk/high gain studies explore novel concepts for monitoring and therapy of yet untreatable stages of MS and other degenerative diseases of the CNS.

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The information about "H I C I" are provided by the European Opendata Portal: CORDIS opendata.

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