Our laboratory investigates the molecular mechanisms underlying flavivirus replication. Flaviviruses are emerging and reemerging mosquito-borne pathogens of global concern, including dengue, Zika, yellow fever, and West Nile viruses. Using dengue and Zika viruses as model systems, we study how the viral RNA genome regulates infection—directing protein synthesis, genome replication, virion assembly, and immune evasion—while adapting to alternate between human and mosquito hosts. Deciphering these processes is critical for identifying barriers to cross-species transmission. A key discovery from our work is the elucidation of the flavivirus RNA synthesis mechanism. We identified the promoter RNA structure and conserved genomic RNA elements essential for replication and genome cyclization, findings that apply broadly across the flavivirus genus. Beyond viral replication, we investigate host-virus interactions that shape infection outcomes. Using proteomics, we revealed how the dengue NS5 protein disrupts host immune defenses, uncovering new aspects of viral immune evasion. Building on these discoveries, we are now developing innovative diagnostic tools to improve detection and control of dengue and other flaviviruses.