Dr. Smith performed his graduate studies at Harvard University in the laboratory of Dr. James Cunningham. His thesis focused on understanding how conformational changes in the envelope glycoprotein of the retrovirus avian leukosis virus A are linked to entry and infection. As a postdoctoral fellow in the laboratory of Dr. Glen Nemerow at the Scripps Research Institute, Dr. Smith studied the mechanisms of action of innate (e.g., defensins) and adaptive (e.g., neutralizing antibodies) immune effectors in neutralizing human adenovirus infection.
The Smith lab is primarily focused on understanding the role of defensins in viral pathogenesis. Defensins comprise a class of antimicrobial peptides with broad antibacterial activity; however, their effects on viral infection, immunity, and pathogenesis, particularly for nonenveloped viruses, are less well understood. Using a variety of approaches from virology, cell biology, biochemistry, structural biology, and genetics, our work is focused on understanding the interaction of defensins with human adenovirus and human papillomavirus in molecular detail to determine general principals of defensin-mediated neutralization of nonenveloped viral infection. We are also interested in using animal models of enteric viral diseases to understand the role of defensins in antiviral immunity in vivo. Finally, we have recently adopted a new 3D intestinal enteroid culture methodology that enables the study of the gut epithelium under more physiologic conditions. We are using this system to examine the interaction of viruses and bacteria with host cells and to study the cell biology of epithelial cell types that were previously unculturable.