BBS Faculty Member - Gerald Pier

Gerald Pier

Department of Medicine

Brigham and Women's Hospital
Channing Labs, 7th Floor
181 Longwood Avenue
Boston, MA 02115
Tel: 617-525-2269
Fax: 617-525-2510
Email: gpier@rics.bwh.harvard.edu
Lab Members: 5 junior faculty, 2 postdoctoral fellows, 2 foreign graduate students
Visit my lab page here.



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 nosocomially-acquired infections caused high antibiotic-resistant organisms. For vaccines, 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 are using modern molecular genetic techniques and models of animal infections to define the contribution of genes, RNA and proteins to bacterial fitness in different settings. The bacterial pathogens currently under investigation include Pseudomonas aeruginosa, Staphylococcus aureus, Staphylococcus epidermidis, E. coli, Klebsiella pneumoniae and Acinetobacter baumannii.

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. Additionally, mechanisms of immunity elicited by live, attenuated vaccines are under investigation.

The major antigen we are investigating as a vaccine candidate is poly-N-acetyl glucosamine (PNAG), an important surface polysaccharide antigen of many different gram-positive and gram-negative organisms. We are evaluating different synthetic glycoforms of PNAG to identify the maximally immunogenic vaccine candidate for development into a conjugate vaccine. Fully human monoclonal antibodies have been made and are in clinical development. We are using these reagents to expand the potential targets of PNAG-based immunotherapy to non-prokaryotic microbes we have discovered that make PNAG.

To study pathogenesis we use high throughput sequencing of saturated transposon libraries created in a number of pathogens and apply system biological analysis to determine the role of all of the genes, there regulatory networks and similar factors in survival fitness in different in vitro and in vivo settings. Complementary results using RNA-seq and similar tools are used to develop a comprehensive understanding of what different pathogens need to express and accomplish to survive, grow and cause infections in mammalian hosts.

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 is a cellular receptors for P. aeruginosa and are investigating how the bacterial-CFTR interaction that occurs in normal hosts leading to effective resistance to P. aeruginosa contributes to the hypersusceptibility of CF patients to P. aeruginosa infection.



Last Update: 8/22/2013



Publications

For a complete listing of publications click here.

 


 

Kowalski MP, Dubouix-Bourandy A, Bajmoczi M, Golan DE, Zaidi T, Coutinho-Sledge YS, Gygi MP Gygi SP, Wiemer EAC, Pier GB. Host Resistance to lung infection mediated by major vault protein in epithelial cells. Science. 2007; 317:130-132.

Skurnik D, Merighi M, Grout M, Gadjeva M, Maira-Litran T, Ericsson M, Goldmann DA, Huang SS, Datta R, Lee JC, Pier GB. Animal and human antibodies to
Staphylococcus aureus capsular polysaccharides and poly-N-acetyl glucosamine mutually neutralize opsonic killing and protection. J. Clin. Invest. 2010.

Pier GB. The challenges and promises of new therapies for cystic fibrosis. J. Exp. Med. 2012;209:1235-9.



© 2013 by the President and Fellows of Harvard College