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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.

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

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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