Gregory Priebe, MD
Dr. Priebe joined the faculty of Children’s Hospital Boston in October 2001. In July 2004, he became the Associate Program Director of the Fellowship Program in Pediatric Critical Care. He also holds the position of Associate Physician at the Channing Laboratory of Brigham and Women’s Hospital, where his research lab is located.
Dr. Priebe earned his medical degree from Harvard Medical School and then went on to complete residency and chief residency in Pediatrics followed by fellowships in Pediatric Infectious Diseases and Pediatric Critical Care, all at Children’s Hospital Boston. He is board-certified in Pediatric Infectious Diseases and Pediatric Critical Care.
Dr. Priebe’s laboratory studies immunity to bacterial lung infections, particularly those caused by the Gram-negative bacterial pathogens Pseudomonas aeruginosa and members of the Burkholderia cepacia complex. P. aeruginosa is an important cause of hospital-acquired infections in critically ill and immunocompromised patients, of corneal infections in wearers of contact lenses, and of chronic lung infections in children and adults with cystic fibrosis (CF) while the Burkholderia cepacia complex causes chronic pneumonia and bacteremia in patients with CF and chronic granulomatous disease.
A major focus of his lab is on the mechanisms of protection from infection following mucosal vaccination with live-attenuated Pseudomonas strains. Pseudomonas mutants having a deletion of the aroA gene, which is required for the synthesis of aromatic amino acids, have proven to be both highly attenuated and immunogenic in mouse models of infection. Dr. Priebe has shown that these live-attenuated vaccine strains given intranasally protect mice against mortality from acute P. aeruginosa pneumonia and also against severe eye pathology from corneal infections. Antibody alone can protect against most corneal infections. However, for protection against pneumonia, both cellular immunity (particularly T cells) and LPS-specific antibodies are needed. He has shown that rapid recruitment of neutrophils to the airways by the T cell-derived cytokine IL-17, produced by a distinct subset of helper T cells called Th17 cells, is critical for effective vaccine-induced protection and can even protect in the absence of LPS-specific antibody.
Dr. Preive has recently utilized a Pseudomonas protein library to identify novel protein antigens that induce T cell secretion of IL-17 and are effective protein vaccines in mice. Current experiments are also assessing the role of IL-17 in immunity to Staphylococcus aureus lung infections. In his Pseudomonas studies, he is exploring a novel phenotype of vaccine-induced airway neutrophils (high ICAM-1 expression) that is associated with less lung injury and enhanced bacterial clearance. Dr. Priebe also demonstrated, in a collaborative project with the Remold-O’Donnell group, that that serpinb1, a neutrophil elastase inhibitor, protects neutrophils from elastase-induced early apoptosis during acute P. aeruginosa pneumonia. Current studies are also dissecting the mechanisms behind the suboptimal antibody response of CF mice to his live-attenuated vaccines and testing ways to improve it.
Another major focus of Dr. Priebe’s lab centers on the development of vaccines and immunotherapies for the Burkholderia cepacia complex (BCC), most notably B. dolosa, which has caused a large outbreak in the CF population at Children’s Hospital Boston. He has found that bacteria in the BCC possess homologs of the genes for a staphylococcal surface polysaccharide called poly N-acetyl-glucosamine (PNAG) and that BCC not only express PNAG in vitro and in vivo but also can be killed by antibodies directed at PNAG. In searching for other potential therapeutic targets for the BCC, Dr. Priebe’s lab collaborated with the Kishony group of the Systems Biology Department at HMS to analyze the whole-genome sequences of 122 B. dolosa isolates recovered over almost 2 decades from the Children’s outbreak. They found adaptive mutations that arose independently in different patients and thereby identified bacterial genes under strong positive selection. These genes illuminate known pathogenic phenotypes, and also implicate novel pathways in pathogenesis.
Stemming from his roles as chair of the Nosocomial Infection Oversight Committee of Children’s Hospital Boston, which oversees infection control practices in the hospital’s 4 ICUs, and as the physician site leader for the Catheter-Associated Bloodstream Infection (CA-BSI) National Collaborative of NACHRI, Dr. Priebe’s lab has recently undertaken a project to assess the optimal disinfection practices for central line caps. The results of these studies will help define both local and national practices around care of central venous lines in children.