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IL7sigNETure SIGNED

IL-7/IL-7R signaling networks in health and malignancy

Total Cost €

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EC-Contrib. €

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Partnership

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 IL7sigNETure project word cloud

Explore the words cloud of the IL7sigNETure project. It provides you a very rough idea of what is the project "IL7sigNETure" about.

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Project "IL7sigNETure" data sheet

The following table provides information about the project.

Coordinator
INSTITUTO DE MEDICINA MOLECULAR JOAO LOBO ANTUNES 

Organization address
address: AVENIDA PROF EGAS MONIZ
city: LISBOA
postcode: 1649 028
website: www.imm.ul.pt

contact info
title: n.a.
name: n.a.
surname: n.a.
function: n.a.
email: n.a.
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 Coordinator Country Portugal [PT]
 Project website https://imm.medicina.ulisboa.pt/en/investigacao/labs/barata-joao-t-lab/
 Total cost 1˙988˙125 €
 EC max contribution 1˙988˙125 € (100%)
 Programme 1. H2020-EU.1.1. (EXCELLENT SCIENCE - European Research Council (ERC))
 Code Call ERC-2014-CoG
 Funding Scheme ERC-COG
 Starting year 2015
 Duration (year-month-day) from 2015-09-01   to  2020-08-31

 Partnership

Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 
1    INSTITUTO DE MEDICINA MOLECULAR JOAO LOBO ANTUNES PT (LISBOA) coordinator 1˙988˙125.00

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 Project objective

Deregulation of signal transduction is a feature of tumor cells and signaling therapies are gaining importance in the growing arsenal against cancer. However, their full potential can only be achieved once we overcome the limited knowledge on how signaling networks are wired in cancer cells. Interleukin 7 (IL7) and its receptor (IL7R) are essential for normal T-cell development and function. However, they can also promote autoimmunity, chronic inflammation and cancer. We showed that patients with T-cell acute lymphoblastic leukemia (T-ALL), an aggressive hematological cancer, can display IL7R gain-of-function mutations leading to downstream signaling activation and cell transformation. Despite the biological relevance of IL7 and IL7R, the characterization of their signaling effectors remains limited. Here, we propose to move from the single molecule/pathway-centered analysis that has characterized the research on IL7/IL7R signaling, into a ‘holistic’ view of the IL7/IL7R signaling landscape. To do so, we will employ a multidisciplinary strategy, in which data from complementary high throughput analyses, informing on different levels of regulation of the IL7/IL7R signaling network, will be integrated via a systems biology approach, and complemented by cell and molecular biology experimentation and state-of-the-art in vivo models. The knowledge we will generate should have a profound impact on the understanding of the fundamental mechanisms by which IL7/IL7R signaling promotes leukemia and reveal novel targets for fine-tuned therapeutic intervention in T-ALL. Moreover, the scope of insights gained should extend beyond leukemia. Our in-depth, systems-level characterization of IL7/IL7R signaling will constitute a platform with extraordinary potential to illuminate the molecular role of the IL7/IL7R axis in other cancers (e.g. breast and lung) and pathological settings where IL7 has been implicated, such as HIV infection, multiple sclerosis and rheumatoid arthritis.

 Publications

year authors and title journal last update
List of publications.
2017 F Buontempo, J A McCubrey, E Orsini, M Ruzzene, A Cappellini, A Lonetti, C Evangelisti, F Chiarini, C Evangelisti, J T Barata, A M Martelli
Therapeutic targeting of CK2 in acute and chronic leukemias
published pages: 1-10, ISSN: 0887-6924, DOI: 10.1038/leu.2017.301
Leukemia 32/1 2019-06-06
2017 Mariana L. Oliveira, Padma Akkapeddi, Isabel Alcobia, Afonso R. Almeida, Bruno A. Cardoso, Rita Fragoso, Teresa L. Serafim, João T. Barata
From the outside, from within: Biological and therapeutic relevance of signal transduction in T-cell acute lymphoblastic leukemia
published pages: 10-25, ISSN: 0898-6568, DOI: 10.1016/j.cellsig.2017.06.011
Cellular Signalling 38 2019-06-06
2018 Mariana L. Oliveira, Padma Akkapeddi, Daniel Ribeiro, Alice Melão, João T. Barata
IL-7R-mediated signaling in T-cell acute lymphoblastic leukemia: An update
published pages: , ISSN: 2212-4926, DOI: 10.1016/j.jbior.2018.09.012
Advances in Biological Regulation 2019-04-18
2018 Daniel Ribeiro, Alice Melão, Ruben van Boxtel, Cristina I. Santos, Ana Silva, Milene C. Silva, Bruno A. Cardoso, Paul J. Coffer, João T. Barata
STAT5 is essential for IL-7–mediated viability, growth, and proliferation of T-cell acute lymphoblastic leukemia cells
published pages: 2199-2213, ISSN: 2473-9529, DOI: 10.1182/bloodadvances.2018021063
Blood Advances 2/17 2019-04-18
2016 Alice Melão, Maureen Spit, Bruno A. Cardoso, João T. Barata
Optimal interleukin-7 receptor-mediated signaling, cell cycle progression and viability of T-cell acute lymphoblastic leukemia cells rely on casein kinase 2 activity
published pages: 1368-1379, ISSN: 0390-6078, DOI: 10.3324/haematol.2015.141143
Haematologica 101/11 2019-06-06

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