Our research focuses on the development of the mammalian hematopoietic system. Of particular interest is the characterization of signal transduction molecules and pathways that regulate T cell maturation in the thymus. Current projects include the generation of transgenic and conditional deletion mutants to evaluate the importance of T cell antigen receptor signaling at specific stages of T cell development. We are also using microarray gene profiling to identify molecules that are important for thymocyte selection, a process that promotes the survival and development of functional T cells and the death of auto-reactive T cells. Further, we are analyzing the function of Themis, a T cell–specific signaling protein newly identified by our laboratory. A recently initiated area of investigation focuses on hematopoietic stem cells (HSCs). We have begun to characterize the genes that are important for the generation and maintenance of HSCs and for their differentiation into specific hematopoietic lineages. These studies have revealed a critical function for one protein (Ldb1) in controlling the self-renewal/differentiation cell-fate decision in hematopoietic stem cells.