Objectif Acute myeloid leukemia (AML) remains a devastating disease, while progress in genetic characterization and nanomedical approaches promise a new era of individualized treatments. To prioritize genetic aberrations in AML for therapeutic targeting and to develop a pipeline for personalized nanomedicines I will i) establish a biobank of transplantable primary human AML xenotransplants, ii) fully characterize the genetic landscape of these leukemias, iii) establish the functional hierarchy of driver and passenger mutations in these human leukemia models, iv) develop highly efficient nanoparticle-siRNA formulations that allow in vivo delivery of siRNA to primary AML blasts, and v) design double specific siRNA-based nanomedicines for improved efficacy and tolerability. The expertise of my research team and my institutional settings and collaborations provide a unique platform to achieve these objectives. My access to freshly isolated leukemia blasts allows efficient establishment of a biobank for AML xenotransplant models. In fact, we can serially transplant and expand primary AML cells in immunodeficient mice. The biobank will be an invaluable resource for pharmaceutical product development. I have extensive experience in the genetic characterization and functional evaluation of leukemic cells, which I will apply to the newly generated human AML models. I will use inducible lentiviral approaches to genetically modify human leukemia cells and observe the functional effects in vivo, to identify the relevant targets for leukemogenicity of each primary AML model. Most importantly, I can formulate nanoparticle-siRNA systems that show unprecedented complete uptake into human leukemia cells in vivo and open the door for specific inhibition of any gene. These established tools provide me with the unique ability to develop a pipeline for individualized nanomedicines that will improve AML treatment and will also have broad applications beyond leukemia treatment. Champ scientifique medical and health sciencesbasic medicinepharmacology and pharmacypharmaceutical drugsmedical and health sciencesmedical biotechnologynanomedicinemedical and health sciencesmedical biotechnologycells technologiesstem cellsmedical and health sciencesbasic medicinepharmacology and pharmacypharmacokineticsmedical and health sciencesclinical medicineoncologyleukemia Programme(s) H2020-EU.1.1. - EXCELLENT SCIENCE - European Research Council (ERC) Main Programme Thème(s) ERC-StG-2014 - ERC Starting Grant Appel à propositions ERC-2014-STG Voir d’autres projets de cet appel Régime de financement ERC-STG - Starting Grant Institution d’accueil MEDIZINISCHE HOCHSCHULE HANNOVER Contribution nette de l'UE € 1 499 750,00 Adresse Carl-Neuberg-Strasse 1 30625 Hannover Allemagne Voir sur la carte Région Niedersachsen Hannover Region Hannover Type d’activité Higher or Secondary Education Establishments Liens Contacter l’organisation Opens in new window Site web Opens in new window Participation aux programmes de R&I de l'UE Opens in new window Réseau de collaboration HORIZON Opens in new window Coût total € 1 499 750,00 Bénéficiaires (1) Trier par ordre alphabétique Trier par contribution nette de l'UE Tout développer Tout réduire MEDIZINISCHE HOCHSCHULE HANNOVER Allemagne Contribution nette de l'UE € 1 499 750,00 Adresse Carl-Neuberg-Strasse 1 30625 Hannover Voir sur la carte Région Niedersachsen Hannover Region Hannover Type d’activité Higher or Secondary Education Establishments Liens Contacter l’organisation Opens in new window Site web Opens in new window Participation aux programmes de R&I de l'UE Opens in new window Réseau de collaboration HORIZON Opens in new window Coût total € 1 499 750,00