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.
Blood is a living tissue composed of billions of red blood cells, white blood cells and platelets that must be constantly replenished by a rare population of self-renewing hematopoietic stem cells (HSCs). Dysregulation of this fundamental process – known as hemopoiesis – causes a variety of hematological malignancies and disorders in humans. The recent demonstration that human HSCs can be expanded in vitro has fueled the hope that mobilization of these cells might provide an alternative therapy for the treatment of hematological disorders such as anemia and thalassemia. Before the full potential of HSCs can be realized, we need to learn what controls their self-renewal and proliferative capacities, as well as the various pathways of differentiation available to their daughter cells.
One major determinant of cell fate are patterns of chromatin condensation that are established during differentiation. In the past few years, great effort has been devoted to the identification of post-translational histone modifications involved in gene regulation. These epigenetic marks work in combinatorial fashion to constitute a “histone code” that regulates chromatin structure and function. The recent work carried out by Julie Lessard’s team now suggests that combinatorially assembled chromatin remodelers of the SWI/SNF family could act in an equally important manner to regulate transcriptional programs of gene expression during hematopoietic differentiation.
Strikingly, their studies demonstrate that some subunits of the SWI/SNF complex are essential for HSC function, while others are required later in the hematopoietic hierarchy for the development of specific blood-cell lineages (i.e. lymphoid, myeloid and/or erythroid). Their work suggests that combinatorial assembly of alternative subunits confers functional specificity to SWI/SNF complexes by allowing the recognition of distinct gene targets during hematopoietic differentiation.
Current investigation involves a combination of cellular and biochemical methods, molecular genetics and proteomics.