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Molecular Bacterial Pathogenesis

Dr. Matthew Waldor

Dr. Waldor, a Howard Hughes Investigator, studies the pathogenicity of several enteric pathogens including Vibrio cholerae and enterohemorrhagic E. coli. His group recently described the process of inflammation and disintegration of intestinal villi in an infant rabbit model of V. parahemolyticus-induced diarrhea. In addition, his laboratory has explored the origins of the Shiga toxin-producing strain of E. coli O104:H4 that was responsible for a recent food-borne epidemic of diarrhea and hemolytic uremic syndrome in Europe. The Waldor laboratory also studies the mechanism of bacterial chromosome replication. They recently identified a multi-domain hub that anchors chromosome segregation and the chemotactic machinery to the bacterial pole.

Dr. Gerald Pier

Dr. Pier’s research group includes Tomas Maira-Litran, David Skurnik, Colette Cywes-Bentley and Tanweer Zaidi. Their research interests encompass 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 their interest in a conserved surface polysaccharide, poly-N-acetyl glucosamine (PNAG), which they and others have found is synthesized by a diverse range of bacterial species, they 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, A. baumannii, B. cenocepacia as well as a fungal and protozoan parasites including Plasmodia spp. In addition, a major research effort is focused on Pseudomonas aeruginosa, an important nosocomial pathogen and cause of serious infections in the setting of cystic fibrosis.

Dr. Tomas Maira-Litran

Dr. Maira-Litran’s research focuses on A. baumannii, K. pneumoniae and others evaluating virulence factors, vaccine candidates and new high-throughput systems for identifying new antibacterial drugs for multi-resistant gram-negative pathogens.

Dr. David Skurnik

Dr. Skurnik’s research investigations focus on neonatal meningitis caused by E. coli K1, group B streptococcus and others in the context of virulence and vaccines as well as using high-throughput DNA sequencing to further explore virulence and immunity to P. aeruginosa.

Dr. Colette Cywes-Bentley

Dr. Cywes-Bentley’s research interests are directed towards moving a fully human monoclonal antibody to PNAG through clinical trials and examining how immunity to PNAG is manifest against the diverse range of pathogens expressing this surface carbohydrate.

Dr. Tanweer Zaidi

Dr. Zaidi’s laboratory investigations are directed to pathogenesis and immune responses to corneal infections, working with the diverse range of pathogens causing serious eye infections and loss of vision and evaluating innate and acquired immune factors that limit infection without exacerbating the destructive, sight-limiting components of inflammation during infection.

Dr. Jean C. Lee

Dr. Jean Lee studies the pathogenesis of infections caused by Staphylococcus aureus. A major focus of her laboratory has been the preclinical evaluation of S. aureus vaccine candidates in rodent models of staphylococcal disease. Her primary effort is directed toward the design and evaluation of a multicomponent S. aureus bioconjugate vaccine expressed in Escherichia coli by glyco-engineering technology. In addition, she has active collaborations (and funding) with laboratories in Chicago and Maryland for the development of other multicomponent S. aureus vaccine candidates.

The Lee laboratory has developed and used animal models of S. aureus colonization and infection to study microbial interactions with the naïve host. In a rodent model of nasal carriage, bacterial factors that promote colonization have been identified, and one of these proteins (clumping factor B) was demonstrated to serve as an effective vaccine candidate to reduce colonization. The gastrointestinal tract is an important reservoir for USA300 isolates of S. aureus that cause community acquired MRSA infections. Dr. Lee has identified a specific gene (arcA) within a newly described mobile genetic element in staphylococci (called ACME) as a factor that increases S. aureus fitness in the gastrointestinal tract.

In collaboration with scientists at the Fraunhofer Institute/Boston University, a microfluidic platform has been developed for stress-induced rapid antibiotic susceptibility testing. The methodology was optimized for S. aureus, and the technology is now being extended to other microbes and antibiotics. In a separate study with the same Fraunhofer collaborator, a novel technology was developed for rapidly identifying microbes in blood samples, based on signals provided by surface-enhanced Raman spectroscopy (SERS). In particular, Dr. Lee is involved in investigating the metabolic and molecular origins of the unique bacterial signatures provided by SERS.


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