Research in the Section on Hematopoiesis and Lymphocyte Biology is focused on elucidating the cellular and molecular processes that regulate mammalian hematopoiesis. Within this broad context, our studies are currently focused in three main areas.

The first area of research, representing a long-term project in the lab, involves characterization of the role of T cell antigen receptor (TCR) signals, and in particular, individual TCR signal transducing subunits and signal transducing motifs in T cell development. These studies employ a number of genetically altered mouse strains generated in our laboratory and elsewhere by gene targeting and transgenic technology. A major advantage of this approach is that it has enabled us to analyze developmental and physiological processes that cannot be addressed with in vitro genetic approaches.

Second, we have begun to identify and characterize the function of other signal transducing molecules that play an important role in T cell development (CCR9, CD5, TLAP). The aim of these studies is to understand how these molecules participate in TCR mediated signaling and to determine what roles they and the signaling pathways they regulate play in T cell maturation, thymocyte selection and T cell activation.

Third, we have initiated a new project that examines the role of Ldb1, a nuclear adapter protein, in hematopoiesis. This study has revealed important functions for Ldb1 in hematopoietic specification, erythropoiesis and hematopoietic stem cell maintenance. The research performed in our lab may provide insights into the pathogenic mechanisms underlying human autoimmune diseases or primary immunodeficiencies. In addition, our results may identify new avenues for treatment of human hematopoietic malignancies. Thus, we believe our research program addresses the missions of both the NICHD and the NIH.