Programming a Killer (CTL)


The overall focus of the Pipkin lab is to elucidate how chromatin structure and transcription controls the gene expression programs that establish and maintain the differentiated states of T cells. The lab specifically studies how naïve CD8 T cells differentiate into effector and memory cytotoxic T lymphocytes (CTL). CTL are killer lymphocytes that hold outstanding promise for controlling viral infections and cancer therapeutically, as they can be employed in adoptive immunotherapy and are the target of successful vaccination.

The Pipkin lab has developed novel approaches to map the fundamental repeating structures of chromatin (nucleosomes) at unprecedented resolution, novel reporter genes to track cells in vivo that induce expression of Prf1, an essential gene that is required for the anti-tumor killing activity of CTL, and the first systems to conduct genome-scale in vivo pooled RNA interference (RNAi) screens in T cells during the course of viral infections. Using these tools and approaches, the Pipkin lab is clarifying how transcription factors govern the specific organization of nucleosomes that enforces CTL differentiation, identifying the chromatin regulatory factors that maintain the differentiated state “epigenetically”, and demonstrating how these processes mediate durable immunity.