B.Sc., in Immunology, University of Toronto, 1989
Ph.D., in Immunology, University of Toronto, 1995
The development of mature hematopoietic cells requires the coordinated activity of many transcription factors that regulate differentiation, proliferation, and survival. My lab is interested in understanding how these processes are controlled during commitment of multipotent hematopoietic progenitor cells to the lymphoid lineages. We have focused on the basic helix-loop-helix transcription factors encoded by the E2A gene and their antagonists, the Id proteins. The E2A gene products are required for proper B and T lymphocyte development whereas Id2 is required for Natural Killer cell and Lymphoid Tissue initiating cell development. All of these lineages are thought to develop from a common lymphoid progenitor (CLP), suggesting that control of E2A activity may play a direct role in the lineage choice of CLPs. We have determined that E2A proteins are required for B-lymphocyte development, in part, because they induce the expression of EBF, another transcription factor that promotes B-lineage commitment. In addition to their role in the regulation of EBF, E2A proteins are required for optimal proliferation and expression of N-myc in response to cytokine stimulation. Therefore, E2A proteins link differentiation of multipotent cells into the B-lymphocyte lineage with the ability to proliferate in response to external factors.
E2A proteins are also required for proper T lympocyte lineage commitment and in their absence only a few T cells develop. Regardless, E2A-/- mice succumb to T cell lymphoma within the first 3-6 months of life. We have identified a number of E2A target genes that may function in T lymphocyte lineage commitment and/or the suppression of T cell lymphoma and we are currently characterizing the function of these proteins in lymphopoiesis.