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mathematical modeling
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Broadly, my group investigates the coevolution of pathogens and hosts’ adaptive immunity. We use computational and mathematical tools to test hypotheses and to advance theory. Our earlier work focused on the evolutionary consequences of immune-mediated competition between different pathogen strains, including pneumococcus, human papillomavirus, and especially influenza. More recently, our focus has expanded to include the related dynamics of the host immune response. We are investigating the evolution of antibody repertoires within hosts over time, in particular to identify the roles of infection history, chance, vaccination, and host genetics in generating the diversity of B cell responses. This research involves linking epidemiological and immunological observations of B cells to the antigenic and genetic evolution of influenza viruses. Consequently, it makes extensive use of longitudinal dynamical models of individuals and birth cohorts as well as techniques from molecular evolution to investigate coevolution across scales.
Understanding the dynamics of vaccination is another area of focus. We have investigated the actual and expected impacts of vaccines against pneumococcus, human papillomavirus, and influenza. With influenza, we have been investigating the impact of the vaccine on viral transmission and local evolution and how immune history might reduce the vaccine’s effectiveness and alter selective pressures. Improving vaccination strategies given hosts’ diverse immune histories and the potential for rapid evolution by the pathogen is a long-term aim of our work. Ultimately, we want to explain coevolution sufficiently well to enable prediction, or at least to determine when prediction is not feasible.
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