Lab Research Focus
My laboratory is interested in the genetic basis of pathogenesis of Streptococcus pneumoniae, an important cause of otitis media, meningitis, and pneumonia. The polysaccharide capsule of S. pneumoniae is a major virulence factor of the organism. However, the role of capsular serotype per se and of non-capsular factors is less clear. In one area of study we are examining the specific role that capsular type plays in virulence. Using molecular genetic techniques we have localized and characterized genes required for capsule expression and have constructed isogenic strains differing only in capsular type. These strains are being used in animal studies to determine whether specific virulence properties are affected by capsular type. These studies will allow us to determine the genetic basis of capsule expression with respect to identity, function, regulation, and evolution.
A second area of study involves pneumococcal surface protein A (PspA), a protection-eliciting molecule that is also a virulence factor of S. pneumoniae. DNA sequence analysis indicated that PspA has four distinct domains. Our studies are directed towards determining the functions of these domains in virulence, variability, and anchoring of the protein to the S. pneumoniae surface. An unusual mechanism of anchoring by PspA has led to studies involving protein secretion and novel systems for expressing and easily purifying heterologous antigens from S. pneumoniae.
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