The innate immune system protects us from infection and cancer. Natural killer (NK) cells are a subset of innate lymphoid cells (ILC) that can detect and eliminate transformed, infected, transplanted, antibody-opsinized, and ‘stressed’ cells. How NK cells achieve self-nonself discrimination requires an understanding of the molecular interactions they use to sense what is harmless or dangerous, and how these molecules assist in the decision to ignore or respond to a target cell under surveillance. Our lab primarily investigates MHC-independent receptor-ligand interactions involving the NKR-P1:Clr (Klrb1:Clec2) recognition system. This paired recognition system includes both stimulatory (NKR-P1A/C/F) and inhibitory (NKR-P1B/D/G) receptors that recognize up/downregulated Clr ligands on target cells. In addition, we recently developed an in vitro cell line model of ILC function (MNK-1/3, which resemble ILC1/3, respectively). This model allows for rapid analysis of gain/loss-of-function genetics directly in ILC by gene overexpression/editing/deletion. The overall goal of the lab is to advance understanding of how receptor-ligand interactions and transcription factor networks affect innate immunity to cancer, infection, and transplantation.