Team: Molecular hematopoiesis
The major goal of the laboratory is to understand how genes are controlled in time and space during dynamic processes such as cellular differentiation and development. We use hematopoiesis, and specifically eythropoiesis, as a biological system to dissect the molecular events leading to fine tuning of gene expression, with strong emphasis on long-range genomic interactions, and associated pathological disorders in erythroid cells.
Our projects aim at unraveling the relationships existing between chromosome folding, genome architecture and gene expression during cellular differentiation and development. 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, which is critical to create dynamic contacts between distal enhancers and target genes in vivo. We focus our attention on the LDB1 transcription factor complex, a major regulator of erythroid differentiation, allowing control of gene expression over long genomic distances (from several kb up to 1 Mb) through the establishment of chromatin loops. These types of long-range interactions are critical in gene regulatory networks and may be affected in several diseases. We showed for instance that long-range enhancer-gene interactions at the HBS1L-MYB locus are affected by genomic variants in beta-thalassemia patients, underscoring the need to decipher such long-range interactions across the genome and to understand their impacts on gene expression.
In this context we are focusing on different erythroid disorders such as beta thalassemias and sickle cell anemia, which are among the most common inherited genetic disorders in humans and acute erythroid leukemias, a rare but particularly aggressive subtype of leukemia for which therapeutic options are dramatically limited.