Immunology Interest Group

Dr. Campbell received his undergraduate degree from the University of Michigan and completed his graduate studies in Nilabh Shastri's laboratory at the Department of Molecular and Cell Biology at the University of California at Berkeley. He then went on to be a postdoctoral fellow in Eugene Butcher's laboratory in the Department of Pathology at Stanford University. He joined the Benaroya Research Institute in Seattle in 2003 as an Assistant Member and was promoted to Full Member in 2015. Dan has made a number of major contributions to our understanding of effector and regulatory T cell functions including the demonstration that effector T cell migration is programed during activation in different secondary lymphoid organs, that regulatory T cell migration to specific non-lymphoid tissues is required for their function, and that regulatory T cells undergo functional differentiation associated with expression of specific T helper cell transcription factors. Lastly, his group has recently characterized the factors and signals that control regulatory T cell abundance and function in different tissue sites. Upon antigen stimulation, T cells integrate signals from the T cell receptor, co-stimulatory molecules, and cytokines that control their clonal expansion and differentiation into short-lived effector cells or long-lived memory cells that help provide protection from re-infection. Correct interpretation of these signals is controlled by various signaling networks, and among these phosphoinositide 3-kinase (PI3K) signaling has a key function in reprogramming cellular metabolism and driving cell proliferation, redirecting cell migration, and controlling the differentiation of effector and memory cells. However, despite the central role of PI3K in normal and pathogenic T cell responses, molecular control of PI3K activation during T cell stimulation remains poorly understood. We have shown that the adaptor protein B Cell Adaptor for PI3K (BCAP) has a critical role in T cell activation, proliferation and differentiation. Although not expressed in naïve T cells, BCAP (encoded by the Pik3ap1 gene) is rapidly upregulated on T cell activation, and our in vitro and in vivo experiments show that BCAP-deficient T cells have defects in antigen-receptor-induced proliferation, signaling and differentiation. These exciting new results support a model in which BCAP acts as an important adaptor protein that modulates PI3K activity in activated CD8+ T cells, thereby controlling their clonal expansion and effector/memory differentiation.