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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.

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

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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