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Gerald Bryan Pier, BA, MA, Ph.D.
Microbiologist, Brigham and Women's Hospital
Professor of Medicine (Microbiology and Molecular Genetics), Harvard Medical School

Brigham and Women's Hospital
Department of Medicine
Infectious Diseases
75 Francis Street
Boston, MA 02115

Research Location: Mass College of Pharmacy Sciences

Research Email: gpier@bwh.harvard.edu

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Research Narrative:

Research Interests: Our research encompasses identification of the molecular basis for the interactions of major human and animal bacterial pathogens with mammalian hosts, with the primary goal being identification of surface antigens eliciting protective innate and adaptive immunity that also contribute to the organism’s virulence.  As a result of our interest in a conserved surface polysaccharide, poly-N-acetyl glucosamine (PNAG), which we and others have found is synthesized by a diverse range of bacterial species, we now are investigating how this molecule plays a role in virulence and immunity to numerous pathogens, including  Staphylococcus aureus, S. epidermidis, E. coli, Y. pestis, K. pneumoniae, B. cenocepacia and others, including recent testing of vaccines to PNAG in economically important animals challenged with natural pathogens.  In addition, the research effort has also focused on Pseudomonas aeruginosa, a major nosocomial pathogen and cause of serious infections in the setting of cystic fibrosis.

 

Our basic research approaches involve understanding the molecular biologic process these bacteria use to produce and regulate virulence factor expression, which encompasses isolation, chemical characterization and evaluation of surface antigens as vaccines, and production and maximization of the biologic properties of human monoclonal antibodies that can be used as passive therapeutic agents to prevent or treat infections with these microbes.  Vaccines targeting the PNAG antigen, as well as fully human monoclonal antibodies, have entered human trials, which will advance our opportunities to understand how and why some many diverse bacterial pathogens produce a conserved surface antigen without facing high-level resistance to infection from humans that are commonly exposed to PNAG.  The vaccine to PNAG was successful in protecting horse foals from Rhodococcus equi infections following vaccination of pregnant mares and pigs against a virulent respiratory pathogen, Actinobacillus pleuropneumoniae. We also study basic aspects of human immunity to infection to identify both infection-resisting and infection-enhancing responses that contribute to the progression of an infection to a serious disease.

 

In regard to P. aeruginosa we have produced and are commercializing with a partner company a fully human IgG 1 monoclonal antibody to alginate with the eventual goal of testing in CF patients for prevention of P. aeruginosa infection.  The MAb underwent successful Phase 1 testing in humans in 2015 and is scheduled for phase II testing in ventilator-associated pneumonia this year.

 

Additional work has focused on identifying factors encoded within the genome of P. aeruginosa that initiates and maintains infection in intensive care patients and cystic fibrosis (CF) patients. Currently we are using high-throughput DNA sequencing to identify genes and gene products needed for virulence in a variety of tissues, with the goal of defining how host factors work to clear P. aeruginosa while bacterial factors counteract the host responses.  In 2015 we published a paper showing acquisition of antibiotic resistance by P. aeruginosa was associated with increased fitness for infection, a finding in contrast to the dogma in the field that antibiotic resistance generally had a fitness cost. Follow up studies on mechanisms whereby antibiotic-resistance impacts microbial fitness are continuing.


Education:
Harvard University, 1997, MA
Univ. Calif. Berkeley, 1976, Ph.D.

Publications (Pulled from Harvard Catalyst Profiles):

1. Ramos Y, Rocha J, Hael AL, van Gestel J, Vlamakis H, Cywes-Bentley C, Cubillos-Ruiz JR, Pier GB, Gilmore MS, Kolter R, Morales DK. PolyGlcNAc-containing exopolymers enable surface penetration by non-motile Enterococcus faecalis. PLoS Pathog. 2019 02; 15(2):e1007571.

2. Rocha JN, Dangott LJ, Mwangi W, Alaniz RC, Bordin AI, Cywes-Bentley C, Lawhon SD, Pillai SD, Bray JM, Pier GB, Cohen ND. PNAG-specific equine IgG1 mediates significantly greater opsonization and killing of Prescottella equi (formerly Rhodococcus equi) than does IgG4/7. Vaccine. 2019 Feb 21; 37(9):1142-1150.

3. Landeta C, McPartland L, Tran NQ, Meehan BM, Zhang Y, Tanweer Z, Wakabayashi S, Rock J, Kim T, Balasubramanian D, Audette R, Toosky M, Pinkham J, Rubin EJ, Lory S, Pier G, Boyd D, Beckwith J. Inhibition of Pseudomonas aeruginosa and Mycobacterium tuberculosis disulfide bond forming enzymes. Mol Microbiol. 2018 Dec 17.

4. Liang X, Gupta K, Quintero JR, Cernadas M, Kobzik L, Christou H, Pier GB, Owen CA, Çataltepe S. Macrophage FABP4 is required for neutrophil recruitment and bacterial clearance in Pseudomonas aeruginosa pneumonia. FASEB J. 2019 Mar; 33(3):3562-3574.

5. Cywes-Bentley C, Rocha JN, Bordin AI, Vinacur M, Rehman S, Zaidi TS, Meyer M, Anthony S, Lambert M, Vlock DR, Giguère S, Cohen ND, Pier GB. Antibody to Poly-N-acetyl glucosamine provides protection against intracellular pathogens: Mechanism of action and validation in horse foals challenged with Rhodococcus equi. PLoS Pathog. 2018 07; 14(7):e1007160.

6. Zaidi TS, Zaidi T, Pier GB. Antibodies to Conserved Surface Polysaccharides Protect Mice Against Bacterial Conjunctivitis. Invest Ophthalmol Vis Sci. 2018 05 01; 59(6):2512-2519.

7. Little DJ, Pfoh R, Le Mauff F, Bamford NC, Notte C, Baker P, Guragain M, Robinson H, Pier GB, Nitz M, Deora R, Sheppard DC, Howell PL. PgaB orthologues contain a glycoside hydrolase domain that cleaves deacetylated poly-ß(1,6)-N-acetylglucosamine and can disrupt bacterial biofilms. PLoS Pathog. 2018 04; 14(4):e1006998.

8. Stevenson TC, Cywes-Bentley C, Moeller TD, Weyant KB, Putnam D, Chang YF, Jones BD, Pier GB, DeLisa MP. Immunization with outer membrane vesicles displaying conserved surface polysaccharide antigen elicits broadly antimicrobial antibodies. Proc Natl Acad Sci U S A. 2018 04 03; 115(14):E3106-E3115.

9. Soliman C, Walduck AK, Yuriev E, Richards JS, Cywes-Bentley C, Pier GB, Ramsland PA. Structural basis for antibody targeting of the broadly expressed microbial polysaccharide poly-N-acetylglucosamine. J Biol Chem. 2018 04 06; 293(14):5079-5089.

10. van Dissel D, Willemse J, Zacchetti B, Claessen D, Pier GB, van Wezel GP. Production of poly-ß-1,6-N-acetylglucosamine by MatAB is required for hyphal aggregation and hydrophilic surface adhesion by Streptomyces. Microb Cell. 2018 Feb 12; 5(6):269-279.