Grant: Operating Grant

The thymus is the essential organ that supports and allows for the development of T lymphocytes from bone marrow-derived stem cells. Thymic contributions result in the generation of mature T cells that are capable of recognizing foreign antigens/pathogens, while at the same time producing T cells that are tolerant to their own uninfected cells, preventing the initiation of autoimmune disease. This proposal provides a comprehensive study of key signaling pathways occurring at a critical checkpoint in T cell development. A deeper understanding of signaling cascades employed during normal T cell maturation is essential, as mutations in components of these signaling pathways may result in oncogenic events, leading to the onset of leukemia, such as aggressive thymomas or lymphomas. Cellular signals and molecular mechanisms underlying the differentiation of immature T cells remain unclear, hence our proposal aims to create in vitro and in vivo experimental systems in which to study the events governing a key stage during T cell differentiation.