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We investigate the pathogenesis of infectious diseases, with a focus on bacterial diseases affecting children. Using a variety of techniques, we are currently attempting to answer questions in four main areas:
Innate immune responses to bacterial colonization
The mucosal surfaces of humans are simultaneously colonized with a vast number of microbial species yet are able to distinguish species, or combinations of species, that may pose a threat. How do the epithelial cells that line these anatomic spaces integrate these signals and initiate innate immune responses? What specific bacterial and host products are essential to proper functioning of this system? How do these responses affect the composition of the normal flora at mucosal surfaces?
Epithelial detection of bacterial toxins
Many bacterial pathogens of humans produce protein toxins that damage or kill host cells at high concentrations. However, it is advantageous for the host to recognize these products while they are at low density and to initiate immune responses before lethal toxin concentrations are present. How do host cells detect and respond to sublethal concentrations of bacterial toxins?
Regulation of epithelial inflammation
Host responses to microbial products at mucosal surfaces are crucial to the timely initiation of immune responses that clear pathogens, yet these responses themselves can damage human tissues and must be tightly regulated. How do epithelial surfaces police their own activation and dampen innate immune responses to avoid excessive inflammation?
Epidemiology of pediatric infectious diseases
How does the initiation of vaccine programs change the epidemiology of both targeted and untargeted diseases within populations? What can we expect as new conjugate vaccines are approved and used?
We are part of the Departments of Pediatrics and Microbiology at Columbia University. We also belong to the Integrated Program in Cellular, Molecular, and Biophysical Studies at Columbia.
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