Zhijian (James) Chen’s research into complex cellular biochemistry has led to the discovery of pathways and proteins that trigger immune and stress responses. Chen has identified proteins, such as the mitochondrial protein MAVS, that are crucial to the body’s defense against RNA viruses such as influenza and Ebola. Now, Chen and his team are dissecting a signaling pathway involving a novel DNA sensor – cyclic GMP-AMP (cGAMP) synthase, or cGAS – which activates an interferon response that may play a role in immune defense against pathogens and malignant cells, as well as in autoimmune diseases such as lupus. Treatment of these autoimmune diseases could involve chemical inhibition of cGAS, whereas cGAMP and its derivatives may be used as adjuvants for vaccines and cancer immunotherapies.
DNA belongs in chromosomes, but some tumors stow cancer-promoting genes outside chromosomes, as ecDNA. New research explores how ecDNA violates genetic norms to fuel many cancers, while also offering hope for turning the tables on these malignancies. Lasker Award honors discovery of the cGAS enzyme and its role in triggering innate immunity. Discoveries by two HHMI investigators show how proteins that organize into liquid droplets inside cells make certain biological functions possible. New studies by HHMI scientists show how cells use sophisticated signaling mechanisms to control production of interferon. HHMI scientists are among 84 newly elected members. Scientists have discovered the molecular pathway responsible for detecting loose bits of DNA outside a cell’s nucleus and setting off an immune reaction.