Regulatory T cells are critical for protection against autoimmune and inflammatory diseases and are under development at UCSF as cellular therapies to treat a wide range of diseases. The genetic underpinnings of Treg identity have been a long-standing area of focus for our work. Recently, the lab has made significant strides to discover genes critical for Treg cell identity and function via CRISPR screening in primary mouse Tregs. We identified novel regulators of FOXP3, including ubiquitin-specific peptidase 22 (USP22), whose modulation in Tregs affects autoimmunity and cancer immunity in mice.
We have also extended CRISPR-based functional genomics to human Treg cells, generating >50,000 single-cell transcriptomes from Tregs subjected to targeted genetic perturbations, revealing uncharacterized transcriptional regulators and downstream gene networks. These studies identify pathways critical for Tregs and demonstrate a broadly applicable functional genomic strategy to discover new targets for Treg immunotherapies.