The major goal of the laboratory is to understand how dynamic 3D genome organization provides a framework for efficient control of gene expression in time and space.
We use hematopoiesis, and specifically eythropoiesis, as a biological system to study how spatial genome conformation evolves during cellular differentiation and development. We aim at dissecting the molecular events controlling chromosome topology and fine tuning of gene expression in normal hematopoiesis and human pathological disorders such as genetic erythroid diseases and leukemia.
We use combination of functional genomics and proteomic tools to dissect the role of transcription factor complexes and chromatin regulatory factors in the establishment of chromatin looping, allowing long-range connections between genes and their distal enhancers. In particular we develop:
- Chromosome Conformation Capture technologies, such as 4C-Seq and Hi-C,
- Chromatin Immunoprecipitation-Sequencing, such as ChIP-Seq and related techniques,
- Proteomics analysis of chromatin associated complexes, using IP-MS and Bio-ID,
- Crispr/Cas approaches for genome editing and generation of knock-in alleles.
This set of complementary approaches is used on mouse and human hematopoietic cells lines, ex vivo differentiated primary human cells and novel mouse models to shed light on the dynamic regulatory network controlling hematopoietic differentiation and erythropoiesis.