Exploring novel pathways governing immunity and leukemia by studying the genetic basis of human myeloid cell defects - from genetics to gene therapy


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 Nazionalità Coordinatore Germany [DE]
 Totale costo 2˙496˙648 €
 EC contributo 2˙496˙648 €
 Programma FP7-IDEAS-ERC
Specific programme: "Ideas" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013)
 Code Call ERC-2010-AdG_20100317
 Funding Scheme ERC-AG
 Anno di inizio 2012
 Periodo (anno-mese-giorno) 2012-01-01   -   2016-12-31


# participant  country  role  EC contrib. [€] 

 Organization address address: GESCHWISTER SCHOLL PLATZ 1
postcode: 80539

contact info
Titolo: Ms.
Nome: Monika
Cognome: Bernhardt
Email: send email
Telefono: +49 89 21803449
Fax: +49 89 2180 2985

DE (MUENCHEN) hostInstitution 2˙496˙648.00

 Organization address address: GESCHWISTER SCHOLL PLATZ 1
postcode: 80539

contact info
Titolo: Prof.
Nome: Christoph
Cognome: Klein
Email: send email
Telefono: +49 89 5160 2811
Fax: +49 89 5160 7702

DE (MUENCHEN) hostInstitution 2˙496˙648.00


 Word cloud

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nejm    endoplasmic    strategies    nat    immunity    human    clinical    gene    therapeutic    myeloid    iquest    leukemogenesis    genetic    murine    defects    pathways    reticulum    cell    function    hax    med   

 Obiettivo del progetto (Objective)

'Genomic system biology approaches offer new aspects to understand the basis of diseases and to develop new therapeutic strategies. Here, we propose to study rare human variants of the immune system to provide novel explanations of mechanisms governing inflammation and leukemogenesis. Following a full circle of translational research, our group has previously defined several novel clinical entities and elucidated their molecular defects (Nat Med 2007, NEJM 2009). Further studies have highlighted the critical role of new pathways for general biological principles (Immunity 2005, Nat Gen 2007, Nat Med 2008). Finally, we have developed innovative gene and cell-based therapeutic strategies and tested their feasibility in clinical trials (JCO 2007, NEJM2009).

The overall goal of ¿Explore¿ is to decipher novel pathways controlling myeloid cell function and leukemogenesis. The following specific aims are proposed: 1. To elucidate genetic defects causing neutrophil disorders in children by homozygosity mapping and to perform functional studies in vitro and in vivo using relevant animal models 2. To identify novel genes controlling endoplasmic reticulum cell function and the secretory pathway in myeloid cells by employing RNA-interference technology 3. To define the role of novel factors involved in controlling the topology of the endoplasmic reticulum and ER-stress in murine model systems 4. To study the role of HAX1 in hematopoisis and leukemogenesis using a new murine HAX1flox allele and to develop a clinical gene therapy approach for patients with severe congenital neutropenia due to HAX1-deficiency

These studies will not only identify novel genetic factors controlling human immunity and leukemogenesis, but may ultimately impact on the development of novel therapeutic strategies.'

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