Research in my lab explores how signal transduction pathways regulate lymphocyte development and activation. A key question is how signaling pathways downstream of these receptors regulate various aspects of B and T cell maturation. Current efforts in the lab seek to elucidate how two such pathways, the Ras and Jak/STAT signaling cascades, entrain these developmental processes. This is being done using a variety of techniques, including retroviral expression strategies and the use of mice expressing dominant negative and activated Ras, Raf and STAT transgenes, in concert with subtractive cDNA libraries and gene microarray technology. To more precisely identify STAT5 gene targets involved in these processes, we have developed a novel, chemical-induced dimerization approach that allows us to selectively activate the STAT5 signaling pathway in the absence of confounding signals from other signal transduction pathways. Using this approach, we hope to identify novel STAT5 targets, in both developing B and T cells, that regulate lymphocyte development and lineage commitment. The other major question we seek to address is how distinct signaling pathways govern lymphocyte activation. For example, we have recently discovered a role for STAT5 signaling in the development of regulatory T cells (Tregs). We are currently studying the molecular mechanisms by which STAT5 alters Treg development and function. In addition, we seek to determine whether Tregs with enhanced STAT5 signaling act as more efficient suppressors of autoimmune disorders such as diabetes, systemic lupus erythematosis, or inflammatory bowel disease.