Julie Lessard and her team focus on the role of the SWI/SNF family of genes with respect to the maintenance, proliferation and differentiation of normal and leukemic hematopoietic stem cells. Her work strives to improve the treatment of leukemia patients.

Research Theme

Blood is a dynamic tissue made up of billions of red blood cells, white blood cells, and platelets, produced daily from a rare population of cells called hematopoietic stem cells (HSCs), which have the ability to self-renew. Deregulation of this fundamental process, known as hematopoiesis, can lead to various pathologies, including hematological diseases and blood cancers.

The recent demonstration of the in vitro expansion of human HSCs derived from cord blood opens up promising prospects for the development of new therapeutic approaches, particularly in the treatment of diseases such as anemia and thalassemia. In order to fully exploit the therapeutic potential of HSCs, it is essential to identify the genetic and epigenetic determinants that regulate their self-renewal, proliferation, and the different differentiation pathways of the cells derived from them.

Research objectives

The chromatin condensation profile that develops during cell differentiation is a key determinant of cell fate. In recent years, significant efforts have identified numerous post-translational modifications of histones involved in gene expression regulation. These epigenetic marks act combinatorially to form a “histone code” that modulates chromatin structure and function.

Recent work by Julie Lessard’s team suggests that the combinatorial assembly of chromatin remodeling complexes of the SWI/SNF family is an equally crucial mechanism in the regulation of gene expression during hematopoietic differentiation. Surprisingly, their studies show that certain SWI/SNF subunits are essential for hematopoietic stem cell function, while others are specifically required for the development of distinct hematopoietic lineages, such as lymphoid, myeloid, and erythroid lineages.

These results indicate that the combinatorial assembly of alternative subunits confers functional specificity to SWI/SNF complexes, enabling the recognition of distinct gene targets and finely orchestrating the transcriptional programs that underlie hematopoietic differentiation.

Ongoing research is based on an integrated approach combining methods from cell and biochemical biology, molecular genetics, and epigenomic and proteomic analyses.