Gerald B. Pier
Department of Medicine
Harvard Medical School
Brigham and Women's Hospital, Channing Laboratory
181 Longwood Avenue
Boston, MA 02115
Tel: (617) 525-2269
Fax: (617) 731-1541
Email: gpier@channing.harvard.edu
Web Page: The Pier Lab Page
4 junior faculty, 4 postdoctoral fellows
We are interested in mechanisms whereby bacterial pathogens cause disease and in defining and testing immune protective mechanisms relevant to prevention of bacterial infection. Specific human diseases of interest include cystic fibrosis (CF), staphylococcal infections and similar nosocomially-acquired infections. A major approach is to purify, characterize and evaluate various bacterial surface capsular polysaccharides as vaccine candidates as well as live, attenuated recombinant strains of bacteria as vaccine candidates. A second approach involves characterizations of the bacterial ligands and host receptors involved in eliminating pathogens from a host mucosal surface. To study mechanisms whereby bacterial pathogens cause disease we produce and characterize various recombinant bacterial strains and evaluate them for their ability to infect animals. The bacterial pathogens currently under investigation include Pseudomonas aeruginosa, Staphylococcus aureus, Staphylococcus epidermidis, E. coli, and Yersinia spp.
Development of vaccines against bacterial infections has been most successful when surface polysaccharides as used as immunogens, but these often have low immunogenicity on their own. Development of polysaccharide-protein conjugate vaccines has thus become a major interest of the lab. For Pseudomonas aeruginosa, the two major surface polysaccharides are lipopolysaccharide O-side chains for strains that cause nosocomial infections and the alginate exopolysaccharide coat of the strains that cause chronic infections in CF patients. Means of inducing immunity specific to these two antigens using live, attenuated and conjugate vaccines are in progress. In addition, in vivo gene expression in immune compromised mice, as determined by microarray analysis, is being used to identify P. aeruginosa virulence factors needed for mucosal colonization and systemic spread. For staphylococci we have found that poly-N-acetyl glucosamine is an important surface polysaccharide antigen of both Staphylococcus aureus and S. epidermidis and can serve as an immunogen to prevent infection. The PNAG antigen is also expressed by E. coli, Y. pestis, Y. pseudotuberculosis, Y. enterocolitica and Burkholderia cenocepacia. This antigen is also being developed as a conjugate vaccine. We are also involved in developing passive immunotherapies by producing recombinant human monoclonal antibodies from cloned human variable region antibody genes.
Another major area has focused on the mechanisms whereby P. aeruginosa initiates infection in CF patients. CF is caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR). We have shown that CFTR itself is a cellular receptors for P. aeruginosa. The implications of this observation in pathogenesis of P. aeruginosa infection in CF are one of the foci of the laboratory’s current interests. We are specifically investigating how the bacterial-CFTR interaction that occurs in normal hosts leads to high-level resistance to P. aeruginosa infection, whereas the lack of this interaction in CF patients leads to hypersusceptibility to P. aeruginosa infection
References: For a complete listing of publications on PubMed, click here.
BBS webpage updated 5/11/2010