In order to recognize diseased and infected cells, T cells require a diverse repertoire of antigen receptors that must distinguish, with exquisite specificity, foreign and mutated antigens from normal self-peptides. Antigen receptor diversity is generated during T cell development in the thymus. Within the thymus, rigorous selection processes accompany T cell differentiation to ensure the functionality and self-tolerance of the unique antigen receptors expressed on individual T cells. Once mature T cells leave the thymus, they encounter a battery of additional checkpoints that regulate their activation in the peripheral lymphoid organs. In addition to their natural role in eliminating abnormal and infected cells, the anti-tumour potential of T cells is being harnessed and re-wired to develop powerful new immunotherapies. Our research program addresses fundamental and translational aspects of T cell development and function. For these studies, we use an array of high-content approaches that allow us to maintain, manipulate, and probe the intact 3-dimensional space of lymphoid tissues. This includes time-lapse imaging of cells in vitro and in situ, mouse and human organotypic culture, genetically engineered mouse models, transcriptome analyses, and multiparametric flow cytometry.