Michael Robert Wessels, M.D.
|Title||John F. Enders Professor of Pediatrics|
|Institution||Children's Hospital Boston|
Infectious Diseases, Enders 761
300 Longwood Ave
Boston MA 02115
|Title||Professor of Medicine|
|Institution||Brigham and Women's Hospital|
Available: 01/03/12, Expires: 06/30/14
Research in our laboratory is concerned with understanding the molecular interactions between pathogen and host in infections due to S. pyogenes (group A Streptococcus, GAS), the etiologic agent of streptococcal pharyngitis (strep throat) and severe invasive infections such as necrotizing fasciitis and streptococcal toxic shock. These bacteria can colonize mucosal surfaces as harmless commensals, but they have the potential to produce local infection or systemic, life-threatening disease. We are particularly interested in the molecular dialog between the bacteria and the human host, and how signaling between them affects the outcome of infection. Specific virulence factors such as the hyaluronic acid capsule and the secreted toxin streptolysin O inhibit uptake and killing of GAS by professional phagocytes (macrophages and neutrophils) and epithelial cells. The expression of these and other virulence determinants is regulated by the CsrRS two-component system in response to specific environmental signals including the human cathelicidin antimicrobial peptide LL-37. Paradoxically, stimulation of LL-37 secretion as part of the host innate immune response appears to signal through CsrRS to upregulate multiple GAS virulence factors, thereby promoting a transition from asymptomatic mucosal colonization to invasive infection.
Possible projects in the lab include determining the role of one or more specific virulence factors in modulating the pathogen-host interaction in model systems such as uptake and killing of GAS by epithelial cells and/or phagocytes; developing an in vitro model system to study how LL-37 affects tissue invasion; or characterization of the molecular interaction between signaling ligands and the CsrS sensor protein or downstream signal transduction. Techniques commonly used in our work include construction of mutant strains of GAS by allelic exchange mutagenesis, expression of recombinant proteins, characterization of gene expression by qRT-PCR, cell culture, and confocal microscopy.
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