My current research activities are centered on the analysis of signaling in CD4+ T cells. Signal transduction in T cells is a highly regulated and coordinated process that can lead to a multitude of potential outcomes initiated by a single stimulus. In my research, I elucidate the cellular and molecular mechanisms that determine whether T cells mature to cytokine-secreting effector cells, undergo apoptosis and clonal deletion, or remain quiescent and potentially are rendered anergic in response to stimulation. Additionally, my lab's research is also targeted towards determining the varying composition of T cell signaling machines (i.e., composed of T cell receptor, co-receptors, co-stimulatory receptors, kinases, proteases, and adapter proteins) in relation to differing extracellular signals (e.g., differences in ligand concentration or binding affinity). The composition of these "signalosomes" may dynamically change in order to fine-tune or alter effector signaling pathways. I believe that a precise understanding of the kinetics of assembly, the dynamics of composition, and the compartmentalization for all signalosomes induced in T cells, as well as a definition of the interactions between different signaling pathways is required for successful, rational vaccine development. To apply a thorough analysis of T cell signaling pathways to vaccine development, I have started collaborating with Drs. Peterson and Chopra, members of the Center, on immune responses to B. anthracis and Y. pestis. Short-term goals are to define immune responses and to determine requirements for the induction of protective immunity in response to challenges with these pathogenic organisms. Our long-term plans include the use of functional genomics and proteomics to characterize the "signalome" – the entire complement of a T cell's signaling molecules and interactions in a temporal and spatial context in response to a challenge with a pathogenic organism.