The goal of my laboratory is to understand the molecular mechanism of the formation of the multiprotein signaling complexes that occur after T cell receptor (TCR) activation.
We are interested in understanding the activation and deactivation mechanism of tyrosine kinases and phosphatases and the role that adaptor proteins play in the regulation and creation of these multiprotein signaling complexes. Currently, my laboratory is focused on four main projects. In the first project, we are investigating the sequence of events that occur during the activation of the adaptor protein LAT, the principle nucleation site for the formation of TCR-induced multiprotein signaling complexes. In the second project, we are characterizing the activation mechanism of the tyrosine kinases Pyk2 and Fak and the role these molecules play in TCR-mediated signaling. In the third project, the function of the adaptor proteins Grb2 in TCR-induced signaling pathways and the formation of multiprotein signaling complexes at LAT is being examined. In the fourth project, we are examining the effects of TLR stimulation on T cell activation and function. These projects employ a range of techniques from biophysical examination of protein-protein interactions to the use of modern imaging techniques to visualize the trafficking of intracellular signaling proteins to the biochemical characterization of signaling event in human T cells. Together, these studies will provide novel insights into the regulation, formation and function of TCR-induced signaling complexes. This information will prove vital not only for understanding the normal immune response to pathogen infection, but also for providing potential targets for the treatment and cure of debilitating diseases of the human immune system.