Our group develops and uses genetic approaches to study processes related to human disease. Recently we have developed an entirely novel genetic model system to expand the toolbox for genetics in human cells. This method enables efficient inactivation of human genes by a single mutation using insertional mutagenesis in cells that are haploid or near-haploid. We have used haploid genetic screens to identify genes that play a role in human disease. Recently we described a new step in the cellular entry route of picornaviruses, a long-sought enzyme that modifies microtubules, an off-switch in the GPCR signaling pathway and a new component of the PD1-PDL1 axis.