Lab Research Focus
The major research interest of my laboratory is to elucidate the molecular mechanism/s by which lymphocyte co-receptors regulate lymphocyte activation and selection with focus on development of autoimmunity.
Currently, our studies focus on the co-receptor CD5 that is expressed on all T cells and a subset of B cells, also described as B1a or CD5+ B cells. The B1a B cell B cell population is the major B cell population responsible for the neonatal repertoire and the natural antibody repertoire in human and mice. CD5 expressing B cell are also the major B cell population from which most B cell leukemias develop. In many autoimmune diseases, including rheumatoid arthritis and Sjögren's syndrome, CD5 expressing B cells are expanded and are responsible for the production of pathogenic autoantibodies. Using CD5-transgenic and CD5-knock out mice, bred into experimentally derived murine autoimmunity animal models, we have now demonstrated that signals transduced by CD5 have a direct effect on B cell selection and development of autoimmunity. Parallel studies from other laboratories and ours also show that CD5 is a key regulator of T cell selection and differentiation. The goal now is to elucidate the molecular mechanisms by which CD5 is able to exert its activity in T and B cells. To address these questions we are developing animal models that express mutant forms of CD5 as a transgene. These mutant CD5-transgenic mice will be used as a source of normal T and B cells to define signal transduction pathways recruited by CD5. Additionally we are also developing models that will enable us to transduce primary B and T cells in vivo and ex vivo using a virus-mediated gene transfer approach.
We predict that by these approaches we will be elucidate molecular mechanisms that are important in regulating lymphocyte selection, activation and differentiation and provide novel approaches to control and treat autoimmune diseases and neoplasias.
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