Interferons constitute a family of cytokine we critical roles in the defense against pathogens, but that also are implicated in autoimmune diseases and cancer. Interferons tightly regulate the expression of a large number of genes, with diverse cellular functions. We investigate the roles of interferon-regulated genes (IRGs) in autoimmune disease and in cancer. By isolating discrete immune cell population from patients and controls followed by gene expression analyses, we obtain a cell-specific map of IRG expression. The function of identified IRGs are investigated both in vitro, using techniques such as lentiviral CRISPR/Cas9 and shRNA, and in vivo using genetically modified mice and xenograft cancer mouse models. To expand the understanding of IRGs we chart the protein interactomes of selected IRGs in immune cells and in cancer cells using proxeome proteomics (e.g. BioID). Furthermore, we use genome-wide CRISPR/Cas9 libraries in cancer cells to identify genes involved in metastasis and drug responses. We aim to identify druggable IRGs that are involved in the pathogenic mechanisms of autoimmune diseases and cancer.