Exhausted T cells lose the ability to proliferate or secrete effector cytokines, express multiple inhibitory receptors (such as PD-1) and are defined by a distinct, abnormal program of gene expression. The focus of the Haining lab is on the transcriptional and epigenetic regulation of the exhausted T cell state. We have found that the differentiation of exhausted T cells occurs with state-specific regulation of genes critical to their dysfunction, offering targets for genome editing that could alter gene expression preferentially in exhausted CD8+ T cells.