Regulation of T cell development in the thymus.

My colleagues and I are studying the regulation of T cell differentiation and lineage commitment in the thymus. Most recently, we have focused on the role of the mitogen-activated protein kinase (MAPK) signaling pathway in these processes and, in particular, the temporal pattern of activation of this pathway and its effect on downstream gene targets. Our data suggest that thymocyte differentiation to either the CD4 or CD8 lineages requires sustained low-level signaling via MAPK, although the latter requires a weaker signal. We have proposed that both the amplitude and kinetics of MAPK signaling may be one aspect of the link between T cell receptor affinity and cell fate. In addition, we have shown that the Egr family of transcription factors is induced as a consequence of MAPK activation during positive selection in the thymus, and we are taking several approaches to identify other genes that are involved in regulating this developmental process.