Objectif "Clonal evolution represents a driving force for cancer cells and a major challenge for therapy. There is a long-standing knowledge that clonal diversification and selection allows cancer cells to pass through distinct steps of transformation. More recently has emerged the concept that ""more malignant"" leukemia subclones can persist after treatment leading to relapse. My research is focused on two diseases which represent privileged models to study clonal evolution: Fanconi anemia (FA), which is a genetic condition predisposing to acute leukemia, and T-cell acute lymphoblastic leukemia (T-ALL), an aggressive leukemia which frequently relapses. The goal of this project is to decipher the crucial molecular and cellular events that drive gain of malignancy and to design new strategies to follow up and treat the patients. Specifically, we aim to:1. Identify the key pathways involved in leukemia progression at two major steps: from pre-leukemia to overt leukemia (in FA), and from primary diagnosis to relapse (in T-ALL). This aim will use high-throughput molecular profiling and functional characterization of longitudinal samples from patients.2. Model leukemia progression in vivo to functionally validate these pathways. We have developed read-outs based on gene silencing in human primary cells from patients followed by leukemia monitoring in immunodeficient mice.3. Define new strategies to prevent the transition towards acute leukemia in pre-leukemic states in FA patients. We will develop new markers for transformation that should help in monitoring therapeutic intervention.4. Test drugs in pre-clinical models to target critical pathways of relapsed ALL. We will use xenografted T-ALL which recapitulates leukemia progression.Completion of this innovative transversal project should markedly improve the knowledge on tumor progression and lead to new strategies to prevent, early detect and/or treat relapse, with the final objective to cure more patients." Champ scientifique medical and health sciencesclinical medicinehematologymedical and health sciencesclinical medicineoncologyleukemia Programme(s) 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) Thème(s) ERC-SG-LS7 - Applied life sciences, biotechnology and bioengineering: agricultural, animal, fishery, forestry/food sciences; biotechnology, chemical biology, genetic engineering, synthetic biology, industrial biosciences; environmental biotechnology. Appel à propositions ERC-2012-StG_20111109 Voir d’autres projets de cet appel Régime de financement ERC-SG - ERC Starting Grant Institution d’accueil Université Paris Diderot-Paris 7 Contribution de l’UE € 1 497 028,00 Adresse Rue Thomas Mann F-75205 / 13 Paris France Voir sur la carte Type d’activité Higher or Secondary Education Establishments Contact administratif Eleonora Zuolo (Ms.) Chercheur principal Jean Soulier (Dr.) Liens Contacter l’organisation Opens in new window Site web Opens in new window Coût total Aucune donnée Bénéficiaires (1) Trier par ordre alphabétique Trier par contribution de l’UE Tout développer Tout réduire Université Paris Diderot-Paris 7 France Contribution de l’UE € 1 497 028,00 Adresse Rue Thomas Mann F-75205 / 13 Paris Voir sur la carte Type d’activité Higher or Secondary Education Establishments Contact administratif Eleonora Zuolo (Ms.) Chercheur principal Jean Soulier (Dr.) Liens Contacter l’organisation Opens in new window Site web Opens in new window Coût total Aucune donnée