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SLIM TERMINATED

Synthetic Lethal Interactions with nucleophosMin 1

Total Cost €

0

EC-Contrib. €

0

Partnership

0

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 SLIM project word cloud

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

designed    first    localization    complement    cellular    aml    malignancies    molecules    screening    chemical    more    hematological    progress    patients    lethal    imaging    elucidation    driver    acute    drugs    therapy    expertise    wild    appear    synthesis    diagnosed    synthetic    35    points    techniques    treatment    multiple    less    vulnerabilities    severe    animal    interactions    survive    mode    small    bear    elucidate    liquid    rounded    molecular    disease    tumor    solid    host    hosting    action    entry    pattern    laboratory    gain    selectively    acting    mutated    proteins    cytoplasm    relapse    biology    biologist    assay    hampered    25    expression    cancers    nucleolar    longstanding    background    researcher    international    npm1    yield    events    therapies    network    mutations    leukemia    collaborations    lack    gene    stable    regimen    cytotoxic    nucleophosmin    expand    kill    myeloid    cells    underlying    uniquely    longer    protein    builds    courses   

Project "SLIM" data sheet

The following table provides information about the project.

Coordinator
CEMM - FORSCHUNGSZENTRUM FUER MOLEKULARE MEDIZIN GMBH 

Organization address
address: LAZARETTGASSE 14 AKH BT 25.3
city: WIEN
postcode: 1090
website: http://www.oeaw.ac.at/

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 Austria [AT]
 Project website https://cemm.at/research/projects/fellowships/ec-msca-postdoc-fellowship-slim/
 Total cost 178˙156 €
 EC max contribution 178˙156 € (100%)
 Programme 1. H2020-EU.1.3.2. (Nurturing excellence by means of cross-border and cross-sector mobility)
 Code Call H2020-MSCA-IF-2015
 Funding Scheme MSCA-IF-EF-ST
 Starting year 2016
 Duration (year-month-day) from 2016-07-01   to  2018-06-30

 Partnership

Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 
1    CEMM - FORSCHUNGSZENTRUM FUER MOLEKULARE MEDIZIN GMBH AT (WIEN) coordinator 178˙156.00

Map

 Project objective

Less than 25% of patients diagnosed with acute myeloid leukemia (AML) survive longer than 5 years. Current treatment regimen are based on non-specifically acting cytotoxic drugs that cause severe side effects. More effective and more specific, targeted therapies are thus needed. Progress, however, has long been hampered by a lack of understanding of the molecular vulnerabilities of the disease.

We here propose to identify and study synthetic lethal interactions with mutations in nucleophosmin 1 (NPM1) in AML. Up to 35% of AML patients bear mutations in NPM1 leading to a localization of this nucleolar protein to the cytoplasm and a characteristic change in gene expression pattern. Moreover, NPM1 mutations appear to be driver events and stable over multiple courses of therapy and relapse. Identifying cellular pathways or proteins that are essential in an NPM1 mutated background but not in NPM1 wild type cells may thus not only contribute to a better understanding of NPM1 biology but also yield entry points for the development of drugs that selectively kill NPM1 mutated AML cells.

We will take an integrated chemical biology approach to first identify small molecules that selectively kill NPM1 mutated over NPM1 wild type cells and then elucidate their mode of action to gain insight into the underlying biology. This project thus uniquely builds on the longstanding experience of the host laboratory and institute in chemical screening, the elucidation of the mode of action of small molecules and in hematological malignancies.

The proposal is designed to complement the experienced researchers current knowledge in chemical synthesis, assay development, solid tumor biology and small animal imaging techniques to become a well-rounded chemical biologist with a disease focus on solid and liquid cancers. The hosting institution will gain from the researcher´s chemical expertise and find opportunities to expand its network of international collaborations.

 Publications

year authors and title journal last update
List of publications.
2017 Berend Snijder, Gregory I Vladimer, Nikolaus Krall, Katsuhiro Miura, Ann-Sofie Schmolke, Christoph Kornauth, Oscar Lopez de la Fuente, Hye-Soo Choi, Emiel van der Kouwe, Sinan Gültekin, Lukas Kazianka, Johannes W Bigenzahn, Gregor Hoermann, Nicole Prutsch, Olaf Merkel, Anna Ringler, Monika Sabler, Georg Jeryczynski, Marius E Mayerhoefer, Ingrid Simonitsch-Klupp, Katharina Ocko, Franz Felberbauer, Leonhard Müllauer, Gerald W Prager, Belgin Korkmaz, Lukas Kenner, Wolfgang R Sperr, Robert Kralovics, Heinz Gisslinger, Peter Valent, Stefan Kubicek, Ulrich Jäger, Philipp B Staber, Giulio Superti-Furga
Image-based ex-vivo drug screening for patients with aggressive haematological malignancies: interim results from a single-arm, open-label, pilot study
published pages: e595-e606, ISSN: 2352-3026, DOI: 10.1016/S2352-3026(17)30208-9
The Lancet Haematology 4/12 2019-06-13
2017 Gregory I Vladimer, Berend Snijder, Nikolaus Krall, Johannes W Bigenzahn, Kilian V M Huber, Charles-Hugues Lardeau, Kumar Sanjiv, Anna Ringler, Ulrika Warpman Berglund, Monika Sabler, Oscar Lopez de la Fuente, Paul Knöbl, Stefan Kubicek, Thomas Helleday, Ulrich Jäger, Giulio Superti-Furga
Global survey of the immunomodulatory potential of common drugs
published pages: 681-690, ISSN: 1552-4450, DOI: 10.1038/nchembio.2360
Nature Chemical Biology 13/6 2019-06-13

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

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