BUSM professor receives Individual Biomedical Research Award

Richard Goldstein, PhD, a professor of pediatrics, division of pediatric infectious diseases, at Boston University School of Medicine (BUSM), has been awarded an Individual Biomedical Research Award by The Hartwell Foundation and will receive $300,000 over three years as a Hartwell Investigator for his project titled, "A Vaccine Against Streptococcus Pneumoniae Based on Bacterial Surface Proteins Phylogenically Certified as Highly Conserved." Goldstein is also director of the section of molecular genetics, Maxwell Finland Laboratory for Infectious Diseases at Boston Medical Center.

Streptococcus pneumoniae (S. pneumoniae or the pneumococcus) is a bacterium commonly found in the nasopharynx (back of the nose) of healthy humans. However, this microbe has also proven to be the most common bacterial species causing pneumonia, invasive meningitis (infection of the fluid surrounding the spinal cord and brain), sinusitis and otitis media (middle ear infection) in children, as well as in elderly and immune compromised populations. The extraordinary evolutionary diversity of Streptococcus pneumoniae has to date, allowed it to eventually circumvent current vaccines. Goldstein proposes a promising alternative vaccine target strategy that would provide universal protection against all known pneumococcal strains.

More than 90 pneumococcal variants with differing outer surface capsule structures shave been identified and traced to differences in the polysaccharides (sugars) making up the coating on the outside of the bacteria. The currently available pediatric vaccine consists of 7-13 of the most common capsular polysaccharide variants responsible for disease, but there is growing evidence the highly variable S. pneumonia is now circumventing this vaccine based on the phenomenon of capsular replacement involving infection by capsular variant-types not included in these vaccines.

Goldstein intends to identify and characterize a new category of vaccine target, referred to as a 'common surface protein', one universal to all the otherwise variant capsular types of S. pneumoniae. The novel foundation of this strategy is his identification of genes coding for such common proteins, that are resistant to mutation, thus invariant throughout the species. He recently published the basis for this finding, revealing that existence of genes within previously unidentified regions of the pneumococcal chromosome that are so essential to survival that variation here proves lethal. As such, these regions, referred to as 'cold spots', could code for invariant outer surface proteins, thus highly promising vaccine targets. Proof of this critical property is to be derived from a unique, world-wide collection of pneumococcal disease isolates of S. pneumonia which Goldstein has organized by evolutionary genetic-relatedness. As such, this organized collection of approximately 1,000 pneumococcal isolates can be used as a template of species evolutionary diversity across which it is possible to test whether indeed a proposed protein vaccine target is in fact 'conserved' across species diversity.

"Boston University and the School of Medicine are very grateful to The Hartwell Foundation for supporting Dr. Goldstein's ambitious and innovative research, mobilizing the power of bacterial evolutionary genetics to develop a vaccine against major cause of child mortality in the US," said Karen Antman, MD, provost, Boston University Medical Campus and dean, Boston University School of Medicine. "Funding for such adventurous, creative research is rare, but it is critical to the research mission of the School and the progress of medicine. Given the competitiveness of the process, funding of a Boston University investigator for the third straight year reflects well on the exceptional quality of our faculty," she added.

"The Hartwell Foundation is pleased to provide financial support to exceptional individuals who are pursuing biomedical research to advance children's health. The ten award winning research proposals in 2009 represent innovative and cutting edge technology from disciplines that include molecular biology, diagnostics, infectious disease, tissue engineering and neurobiology," said Frederick A. Dombrose, PhD, President of The Hartwell Foundation.

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