Objective
Anthracyclines, in particular doxorubicin, are the most effective anticancer drugs. However, their serious side effect is a cardiotoxicity, which is not entirely understood. We propose a novel hypothesis, namely that anthracycline-induced cardiac damage is related to impaired cellular responses to energy depletion, and possibly also to other forms of stress (oxidative, genotoxic), inducing a “catastrophe”, fatal for cardiac (and cancer) cells. The aim of the project is to verify this hypothesis in different models: perfused heart, cultured cardiomyocytes, and an in vivo model of cardiotoxicity newly established in our group, the doxorubicin-treated rat. Our project will integrate: (i) a non-biased phosphoproteomic approach extending our transcriptomic study and aiming at the identification of new phosphorylation events mediating response to doxorubicin; (ii) a targeted approach focusing on pathways identified by our targeted and non-biased in vitro studies, as e.g. signaling by LKB1-AMPK-mTOR, MAPK, HIF, VEGF, and NDPK, a metabolic kinase that we have recently identified as doxorubicin target. We will analyse the effects of doxorubicin on these pathways (including gene and protein expression, phosphorylation, activity) and their consequences for cardiac function, energy state, apoptotic status, and response to an additional stress (ischemia). This multidisciplinary project will combine biophysical, biochemical, molecular, physiological and systems biology (phosphoproteomics, modeling) state-of-the-art approaches. We expect to identify new signaling pathways mediating doxorubicin cardiotoxic action. Further integration of the fellow with the host will allow full valorisation of projects initiated during the present Marie-Curie Fellowship, further supervision of PhD and master students, and access to a permanent position in Grenoble at the group leader level. This would enable the fellow to pursue a dual academic career with her spouse at the same geographic location.
Fields of science (EuroSciVoc)
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: https://op.europa.eu/en/web/eu-vocabularies/euroscivoc.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: https://op.europa.eu/en/web/eu-vocabularies/euroscivoc.
- natural sciences biological sciences biochemistry biomolecules proteins
- medical and health sciences clinical medicine oncology
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Programme(s)
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
Topic(s)
Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
Call for proposal
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
FP7-PEOPLE-2009-RG
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Funding Scheme
Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
Coordinator
38041 GRENOBLE
France
The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.