We study the ecological, evolutionary, and within-host dynamics of RNA viruses using quantitative approaches. These quantitative approaches include the development and simulation of mathematical models, as well as statistically fitting these models to data. Our focus is on viruses affecting humans, particularly influenza and dengue viruses.
Our research program spans several general topics of inquiry: (1) Understanding the interplay between viral evolution and the epidemiological spread of viral infectious diseases. Research on this topic focuses on understanding patterns of antigenic and genetic evolution of partially-immunizing viruses such as influenza, where disease spread impacts herd immunity levels, which in turn drive selection pressures on viral evolution. (2) Understanding constraints on viral adaptation. We have used both modeling and statistical analyses of viral sequence data to identify factors that limit the ability of viruses such as influenza to adapt to new or changing environments. Some of the factors we have examined include transmission bottlenecks and constraints imposed by genetic linkage. (3) Understanding how the genetic and genomic diversity of RNA viruses impacts within-host viral dynamics and onward transmission potential. We have worked on developing modeling approaches to consider how viral diversity within a host interacts to yield collective infection phenotypes, especially in the context of cellular coinfection. (4) Understanding interindividual variation in within-host viral dynamics and evolution. Considerable heterogeneity exists across hosts in their susceptibility, infectivity, and response to infection with viral pathogens. With analyses of dengue virus and influenza virus, our group has examined the causes and consequences of this heterogeneity with a focus on how host immune status, as determined by infection history, impacts selection pressures experienced by a viral population within a host. (5) Understanding the impact of control measures on the epidemiological and evolutionary dynamics of viral infectious diseases. Our group has contributed to understanding the potential effects of disease control for both dengue virus and influenza virus, with a focus on how vector reduction, immunization, and novel therapeutic control efforts will impact disease burden.