Hematopoiesis is a model of differentiation that enables us tostudy the molecular mechanisms involved in the transition from a highly regulated system, in terms of bothhomeostasis and differentiation, to a deregulated system leading to proliferative syndromes or leukemias.
In this context, we are particularly interested inidentifying the mechanisms, pathways and protein players initiated by transforming mutations in protein kinases such as KIT and FLT3, and their impact in various pathologies linked to this receptor (hemopathies, mastocytosis, gastrointestinal stromal tumors - GIST, melanomas). We are also studying other original kinases of interest in oncology: CDK6, FES and FER.

Our project is based on three main approaches in which we have recognized expertise:

• Functional identification of activating mutations in receptors. This expertise, acquired with KIT in mastocytosis, forms the basis for collaborative projects with clinical research teams. We also search for mutations affecting other therapeutic targets, in particular kinases, in other tumor pathologies.

• The search for the involvement of new specific substrates/pathways linked to oncogenic signaling, downstream of activated Receptor Tyrosine Kinases, using proteomics or siRNA approaches. Our expertise in gene transfer in hematopoietic progenitors is a major asset in this functional approach.

Contribution to the identification and characterization of tyrosine kinase inhibitors, in collaboration with AB Science. We are involved in the optimization of kinase-selective compounds of interest in targeted therapy. Our ambition is to identify new therapeutic pathways or targets, by combining our expertise and collaborations.

Our work covers both basic and translational research . To this end, we have access to numerous human and mouse cell models, 3D in vitro cell models, mouse models of hematological diseases, and access to primary patient samples.