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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.

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

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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