Orvedahl Lab

Our lab seeks to understand how immune responses are restrained to prevent potentially fatal overwhelming immune responses. We use in vitro and in vivo approaches for discovery of genes that regulate the cellular response to cytokines and inflammatory triggers, and investigate these factors in models of human disease. We found the cytoplasmic recycling pathway of autophagy protected macrophages against cytokine-induced cell death and mice against fatal cytokine storm syndrome. Preliminary findings point towards a critical intersection of these processes with immunometabolism. We are leveraging a robust and expanding set of genetic toolkits to dissect the pathways leading to protective vs. pathogenic mechanisms in cytokine storm syndromes triggered by various etiologies including SARS-CoV-2. The ultimate goal is to develop host-directed therapies for infectious and inflammatory disorders.