My laboratory group is interested in host-pathogen
interactions and is using genetic methods, protein
chemistry, X-ray crystallography, high-resolution
microscopy, and microarray analysis to study the
molecular and cellular determinants of disease due
to Haemophilus influenzae, a model mucosal
pathogen and a common cause of local respiratory
tract disease and serious invasive infection. H.
influenzae expresses a number of adhesive proteins
that mediate interaction with host epithelium, and
we are studying the biogenesis, adhesive specificity,
and regulation of these proteins. H. influenzae is
also capable of entering and surviving inside host
cells, a strategy that may have evolved to provide
the organism with a protected niche. In ongoing
work, we are examining the host cell receptors, cytoskeletal
elements, and signaling molecules involved in cellular
entry. Recent evidence indicates that H. influenzae forms
biofilms, complex communities of organisms that likely
facilitate persistence on the respiratory epithelial
surface. We are seeking to understand the bacterial
and host factors that influence H. influenzae biofilm
formation, and we are beginning to study the relationship
between biofilms and evasion of innate immune mechanisms,
such as cationic peptides, lactoferrin, and phagocytosis. Using H.
influenzae and human DNA microarrays, we hope
to uncover novel pathways that are fundamental to
the outcome of encounters between bacteria and the
human host. From a practical perspective, our work
has relevance to development of novel antimicrobial
compounds and to generation of a vaccine broadly
effective against H. influenzae.
In a new line of investigation, we have initiated
studies of Kingella kingae, an emerging pathogen
that has been recognized in recent years as a
common cause of invasive disease in young children,
especially bone and joint infections. K. kingae initiates
infection by colonizing the upper respiratory
tract, then invades the bloodstream and disseminates
to distant sites. We have focused on defining
the bacterial and host determinants of colonization,
invasion of the bloodstream, survival in the
intravascular space, and induction of an inflammatory
response.
