Skip to contents

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



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. Roux D, Weatherholt M, Clark B, Gadjeva M, Renaud D, Scott D, Skurnik D, Priebe GP, Pier G, Gerard C, Yoder-Himes DR. HOST IMMUNE RECOGNITION OF THE EPIDEMIC CYSTIC FIBROSIS PATHOGEN BURKHOLDERIA DOLOSA. Infect Immun. 2017 Mar 27.

2. Yu L, Hisatsune J, Hayashi I, Tatsukawa N, Sato'o Y, Mizumachi E, Kato F, Hirakawa H, Pier GB, Sugai M. A Novel Repressor of the ica Locus Discovered in Clinically Isolated Super-Biofilm-Elaborating Staphylococcus aureus. MBio. 2017 Jan 31; 8(1).

3. Søe NH, Jensen NV, Jensen AL, Koch J, Poulsen SS, Pier GB, Johansen HK. Active and Passive Immunization Against Staphylococcus aureus Periprosthetic Osteomyelitis in Rats. In Vivo. 2017 01 02; 31(1):45-50.

4. Zhao G, Zaidi TS, Bozkurt-Guzel C, Zaidi TH, Lederer JA, Priebe GP, Pier GB. Efficacy of Antibody to PNAG Against Keratitis Caused by Fungal Pathogens. Invest Ophthalmol Vis Sci. 2016 Dec 01; 57(15):6797-6804.

5. França A, Pérez-Cabezas B, Correia A, Pier GB, Cerca N, Vilanova M. Staphylococcus epidermidis Biofilm-Released Cells Induce a Prompt and More Marked In vivo Inflammatory-Type Response than Planktonic or Biofilm Cells. Front Microbiol. 2016; 7:1530.

6. Ferreirinha P, Pérez-Cabezas B, Correia A, Miyazawa B, França A, Carvalhais V, Faustino A, Cordeiro-da-Silva A, Teixeira L, Pier GB, Cerca N, Vilanova M. Poly-N-Acetylglucosamine Production by Staphylococcus epidermidis Cells Increases Their In Vivo Proinflammatory Effect. Infect Immun. 2016 Oct; 84(10):2933-43.

7. França A, Pier GB, Vilanova M, Cerca N. Transcriptomic Analysis of Staphylococcus epidermidis Biofilm-Released Cells upon Interaction with Human Blood Circulating Immune Cells and Soluble Factors. Front Microbiol. 2016; 7:1143.

8. Guillard T, Pons S, Roux D, Pier GB, Skurnik D. Antibiotic resistance and virulence: Understanding the link and its consequences for prophylaxis and therapy. Bioessays. 2016 Jul; 38(7):682-93.

9. Kar S, Arjunaraja S, Akkoyunlu M, Pier GB, Snapper CM. Distinct Mechanisms Underlie Boosted Polysaccharide-Specific IgG Responses Following Secondary Challenge with Intact Gram-Negative versus Gram-Positive Extracellular Bacteria. J Immunol. 2016 Jun 01; 196(11):4614-21.

10. França A, Carvalhais V, Vilanova M, Pier GB, Cerca N. Characterization of an in vitro fed-batch model to obtain cells released from S. epidermidis biofilms. AMB Express. 2016 Mar; 6(1):23.