The general aim of the team is to investigate how the 3D conformation and organization of the genome with the cell nucleus functionally contributes to the regulation of gene expression and V(D)J recombination during normal and pathogenic hematopoiesis as well as during immune response.
Modulation of chromatin environments, non-coding RNAs, 3D genome conformation and nuclear organization is tightly linked to the establishment and maintenance of cell-type specific transcription profiles during development and homeostasis, as well as the regulation of nuclear functions like DNA recombination and repair. It is becoming increasingly clear that alterations in these epigenomic features are linked to numerous diseases, in particular cancer. However, the functional relationships between epigenomic mechanisms, cell differentiation, DNA recombination and malignant transformation remain unclear.
The hematopoietic compartment represents a remarkable system, being the key-differentiation program to allow the daily release of billions of blood cells but where each step may lead to blood cancer formation (leukemia/lymphoma). Although epigenomic features have been correlated with the regulation of these programs, their functional role and the consequences of their alterations in the origins of diseases are still largely unknown. The project of the team is to explore these key questions to provide insights into the role of genome and nuclear dynamics in gene regulation and the preservation of genome and cell integrity.
A state-of-the-art combination of single cell analyses and genome-wide approaches are used to investigate: (1) the functional impact of nuclear organization and 3D-genome conformation on V(D)J recombination of antigen receptor loci and maintenance of genome stability, (2) the functional role of regulatory elements and 3D-genome conformation on hematopoiesis and leukemia, and (3) the role of X-linked gene escape from X-inactivation in humoral immunity and automimmunity.