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HepatoRiSK TERMINATED

A new tumor suppressor role for RSK2 in hepatocellular carcinoma

Total Cost €

0

EC-Contrib. €

0

Partnership

0

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 HepatoRiSK project word cloud

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

validated    function    stepping    injection    patient    acute    partly    cas9    reagents    back    mutated    hampers    inhibit    editing    raf    lab    liver    found    vein    fellowship    independent    dependent    landscape    genetics    techniques    assistant    genetic    responsibilities    genome    inhibitor    nearly    ranks    frequently    carcinoma    formal    hcc    suppressor    hepatocellular    cancer    co    tail    model    poor    mutations    samples    aberrations    ras    phenotypic    gene    activates    context    vitro    potently    unexpectedly    mice    whereby    mechanistic    functionally    supervision    mouse    hydrodynamic    therapies    professor    molecular    options    biochemical    hypothesize    months    subject    crispr    rsk2    stone    kinase    genes    cells    me    tumor    worldwide    kinases    mapped    combines    revealed    career    host    mechanism    feed    erk    postdoc    intervention    sequencing    altogether    elucidate    adult    treatment    mutating    acting    mortality    uncover    performed    mechanisms    limited    basis    models   

Project "HepatoRiSK" data sheet

The following table provides information about the project.

Coordinator
KOBENHAVNS UNIVERSITET 

Organization address
address: NORREGADE 10
city: KOBENHAVN
postcode: 1165
website: www.ku.dk

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 Denmark [DK]
 Total cost 212˙194 €
 EC max contribution 212˙194 € (100%)
 Programme 1. H2020-EU.1.3.2. (Nurturing excellence by means of cross-border and cross-sector mobility)
 Code Call H2020-MSCA-IF-2014
 Funding Scheme MSCA-IF-EF-ST
 Starting year 2015
 Duration (year-month-day) from 2015-10-01   to  0000-00-00

 Partnership

Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 
1    KOBENHAVNS UNIVERSITET DK (KOBENHAVN) coordinator 212˙194.00

Map

 Project objective

Hepatocellular carcinoma (HCC) ranks third in cancer mortality worldwide. In spite of this, effective treatment options are limited, partly due to a poor understanding of the molecular basis of HCC, which hampers development of targeted therapies. Recently, cancer genome sequencing mapped the landscape of genetic aberrations in HCC and unexpectedly revealed the kinase RSK2 as the most frequently mutated gene in the RAS-RAF-ERK pathway. I hypothesize that RSK2 is a tumor suppressor in HCC by acting as a feed-back inhibitor of the RAS-ERK pathway, since I find that RSK2 mutations are nearly all loss-of-function and that RSK2 loss potently activates ERK kinases in liver cells. The goal of this proposal is to functionally establish RSK2 as a novel and important tumor suppressor in HCC and identify the mechanism(s) whereby RSK2 may feed-back inhibit the RAS-ERK pathway to promote this cancer. This will be achieved through modelling RSK2 loss in liver cells in vitro and in mice. Among other approaches, I will model RSK2-dependent HCC development by mutating genes found co-mutated with RSK2 directly in the adult mouse liver via hydrodynamic tail vein injection of CRISPR/Cas9 reagents, which may cause HCC within months. I will subject cells and mouse models to mechanistic biochemical and phenotypic studies to elucidate the role and mechanism of RSK2 as a tumor suppressor in HCC. Key findings will be validated in HCC patient samples. The work will be performed in the context of my new role as assistant professor in the host lab, where I will be given formal supervision and management responsibilities. The work combines my postdoc experience in cancer genetics with my host´s beyond-state-of-the-art CRISPR/Cas9 genome editing techniques. Altogether, this fellowship has the potential to uncover new mechanisms for targeted intervention in HCC. Furthermore, it will be an important stepping stone for me towards an independent research career.

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

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