Our lab employs molecular, biochemical, structural, cell biological, and genetic approaches to uncover mechanisms underlying viral pathogenesis and host innate immunity. Our research focuses on the early immune responses to RNA viruses, particularly the regulation of type I interferons (IFNs) and proinflammatory cytokines. We have made pivotal contributions to understanding RIG-I-dependent antiviral signaling, demonstrating that it occurs on mitochondria-associated membranes (MAMs), where signaling complexes form stable “signalosomes” to drive IFN production. More recently, our studies have highlighted the critical role of 14-3-3η, a chaperone protein, in promoting MDA5 oligomerization and intracellular redistribution during antiviral responses. Importantly, we discovered that MDA5 activation triggers Caspase-3-dependent cleavage of 14-3-3η. This cleaved form binds MDA5 more effectively but inhibits signaling by disrupting post-oligomerization processes and impairing trafficking. These findings illuminate a novel temporal regulatory mechanism of MDA5 in antiviral immunity. Building on this, we are now exploring how conserved features of 14-3-3 family members and other post-translational modifications regulate RIG-I-like receptor pathways and type I IFN induction. Our broader goals include characterizing new regulatory factors and signaling dynamics that influence antiviral defense mechanisms. In parallel, we collaborate on innovative technologies, such as microfluidic and digital platforms, to enhance viral diagnostics and disease detection. Our research has appeared in leading journals, including PLOS Pathogens (2024, 2019), Science Signaling (2021), Journal of Virology (2021, 2020), and Lab on a Chip (2024). These findings have shaped the field of antiviral innate immunity and continue to guide new approaches to combat viral diseases.
