The Smith lab has investigated a wide range of topics over the years with an emphasis on structural biology and biochemistry. Some of the projects include rhinovirus complexed with drugs and antibodies, alphavirus structure and antibody neutralization, antifungal proteins and their effects on calcium channels, carbohydrate processing machinery in human microbiota, and the role of glutamate dehydrogenase in insulin hemostasis.

 The current focus of the laboratory is on the role of norovirus capsid flexibility in infection and pathogenesis. They have shown that norovirus has a unique ability to change its structure depending on its environment. The low pH and high concentrations of metal ions and bile salts in the gut cause conformational changes in the capsid that enhance receptor binding while blocking antibody binding. As the virus exits the gut lumen, the virus switches to a conformation with lower affinity for receptor and it is this structure that is recognized by the immune system. In this way, the virus can reversibly block immune recognition in the gut without the need for escape mutations. Work is underway to further prove this hypothesis and its possible role in the transient adaptive immune response in human norovirus infections and the limited tissue tropism in norovirus infections.