Senior Scientist
Division of Stem Cell and Developmental Biology Ontario Cancer Institute
Keywords: signal transduction, transgenic, development of immunity, cell death, lymphocyte, gene regulation, B cell
Research Interests
B Cell Development
B lymphocytes produce antibodies and present antigens. They are essential components of the immune response. Failure to regulate the growth, development, and response of B cells can lead to malignancy, immunodeficiency and autoimmunity. Our research efforts are directed towards a better understanding of the process of B cell commitment and the events that allow progression along the B cell pathway. Cellular, biochemical, and molecular techniques are utilized to achieve our research aims.
1. The Genetic Basis of B cell Commitment and Developmental Progression: Progenitor cells that are poised at various restriction points along the B cell pathway have been identified and cloned. A variety of molecular techniques, including SAGE analysis, differential display, and microarray profiling are used to exam gene usage patterns before and after the sequential stages of commitment. The goal of these studies is to identify genes involved in commitment and subsequent progression of cells along the B cell development pathway.
2. Cellular Interactions and Biochemical Mediators That Promote Development: B cell development is dependent on growth and differentiation factors. In some cases, such factors are produced by stromal cells. We are determining the biochemical nature of the cell-bound and secreted molecules that mediate these interactions.
We have also identified interactions that occur between developing B cells themselves. These homotypic interactions appear to be critical for progression from the pre -B to the B cell stage of development. We are examining the B-B interactions using biochemical techniques as well as optical techniques such as confocal microscopy and optical tweezers.
Finally, we are undertaking signal transduction experiments that seek to determine the interactions between molecular pathways regulated by critical cell surface receptors such as the pre B Cell Receptor and the IL-7 Receptor.
3. Immune System and Disease: We are examining synovial fluids and tissues from patients with Rheumatoid Arthritis to characterize more accurately the interactions between synoviocytes and lymphocytes. We have characterized a large number of synovial cell lines and raised monoclonal antibodies to many of these. Antibodies that activate synovial cells to release proinflammatory cytokines are of particular interest.
We also study B cell maligancies in both mouse and human models. Of specific interest is determining the mechanisms of action of the immune system in recognizing and destroying tumour cells.
