Each partner in a host-pathogen antagonistic interaction employs
specialized strategies, the host to respond to and combat the pathogen,
and the pathogen to circumvent these host defenses. Indeed, the
ultimate success of an infectious agent is often determined by the
interplay between these competing strategies at the early stages of
infection. Host defenses can be general and directed against many
pathogens, or conversely, dedicated to individual threats; while
pathogen mechanisms can exploit normal host processes by interfering
with their regulation or activity.
Laboratory focuses on the development of improved clinical treatments
to prevent, halt or limit bacterial infections at an early stage,
specifically those caused by the human opportunistic bacterium
Pseudomonas aeruginosa. Research into the P. aeruginosa host-pathogen
interaction has both basic and practical importance: this bacterium
infects a remarkably broad array of species, including plants, insects,
and vertebrates; and it is a major agent of grave drug-resistant
infections in trauma, cystic fibrosis, and immunocompromised patients,
including those suffering of, severe burn injuries, or cancer patients
undergoing radiation therapy or chemotherapy.
Our research has
two ultimate goals: (1) to elucidate mechanisms of bacterial
pathogenesis, and (2) to identify host defense pathways. Thus, we seek
to identify pathogen and host mechanisms that respectively mediate or
restrict P. aeruginosa pathogenesis, and ultimately to develop
host-protective interventions that manipulate the identified pathways.
pioneered the use of non-vertebrate hosts to study human microbial
pathogenesis and demonstrated that the opportunistic bacterium P.
aeruginosa can cause disease in both plants and animals using a shared
subset of virulence factors. The identification of conserved mechanisms
of pathogenesis enabled systematic high-throughput identification of
critical pathogenicity factors and indicated that therapeutics for
treating infections can be developed in genetically tractable model
hosts. We use plants,
yeast and insects, as adjunct to mice, to investigate
the genetic and molecular bases of P. aeruginosa virulence. This
non-vertebrate host approach allows human pathogenesis to be modeled in
experimentally amenable organisms in a high-throughput manner. Our
ability to genetically manipulate both pathogen and host permits
concentrated examination of virulence-defense interactions.