Dr. E. John Wherry is the Director of the Institute for Immunology and Professor of Microbiology at the University of Pennsylvania. Dr. Wherry’s expertise focuses on T cell exhaustion in chronic infections and cancer. Dr. Wherry’s work has defined the molecular mechanisms of T cell exhaustion, including defining the role of inhibitory receptor biology, transcriptional control of regulation of T cell differentiation. Much of the efforts in his lab are focused on the mechanisms “checkpoint” pathways such as PD-1 in preclinical models and in human trials. This work has defined the key principles about inhibitory receptor blockade and co-blockage to reverse T cell exhaustion. Dr. Wherry’s work has also defined central transcriptional and epigenetic pathways in the biology of exhausted T cells. A current goal is to define how overall immune function and “Immune Health” are related to development and response to immunotherapies in cancer and other diseases. Major efforts are devoted to transcriptional profiling, genomics and computational biology and multiparameter flow cytometry to understand the nature and reversibility of T cell exhaustion and other forms of T cell and immune perturbation in preclinical and clinical settings.