LABORATORY OF VIROLOGY AND INFECTIOUS DISEASE

William M. Schneider is a Research Assistant Professor in the Laboratory of Virology and Infectious Disease. He investigates how viruses and endogenous genetic elements replicate, interact with cellular machinery, and engage with host defenses. His research focuses on hepatitis B virus (HBV), a major cause of liver disease and cancer, and LINE-1 retrotransposons, mobile genetic elements that make up a substantial portion of the human genome. Although biologically distinct, both rely on RNA intermediates and reverse transcription to generate DNA, providing opportunities to investigate common principles of replication across these systems.

One major focus of Schneider’s research is understanding how HBV regulates the production of its proteins and replication of its genome. Schneider and colleagues developed an RNA-based experimental system that enables them to study early steps in HBV replication independently of viral entry and transcription. Combining this approach with deep mutational scanning, they uncovered the molecular basis of a long-standing phenomenon known as cis preference, in which the viral polymerase preferentially acts on the RNA from which it was produced. In ongoing work, they use high-throughput functional genomics approaches to investigate how viral RNA sequences and structures regulate gene expression and genome replication, and to identify host factors that influence these processes.

A second focus is the replication of human LINE-1 retrotransposons and their interactions with host cells. Building on their work with HBV, Schneider and colleagues developed an RNA-based system to investigate early events in LINE-1 replication. Their studies have identified unexpected forms of LINE-1 DNA synthesis. Current research seeks to define the molecular mechanisms underlying these processes and determine how LINE-1 activity may contribute to innate immune activation and cellular dysfunction.