SYNOPSIS OF AREA OF INTEREST: Molecular determinants of pathogenesis and biofilm development; Regulation of gene expression; Host pathogen interactions, Vaccine development, Innate and adaptive immunity.
AREAS OF INTEREST:
1. Functional Genomics.
We have identified and published on several new genes and loci in Bordetella. We are currently utilizing in vitro systems, cell culture and mouse models (including knockout and immuno-deficient mice) to study their role in controlling gene expression, cellular adhesion, resistance to host defenses and respiratory tract colonization.
2. Development of effective vaccines.
Alum, the current adjuvant in acellular pertussis vaccines fails to elicit appropriate immune responses for optimum protection against Bordetella pertussis, the human pathogen. Thus, substitution of alum with an adjuvant that induces Th1-type responses may increase vaccine efficacy. We have identified Bordetella Colonization Factor A (BcfA) as such an immune-stimulatory factor. BcfA has adjuvant function and induces Th1 type T cell responses. We are currently testing the ability of BcfA to enhance immune responses to current pertussis vaccines. We are also developing veterinary vaccines for Bordetella bronchiseptica, the causative agent of kennel cough in dogs and respiratory diseases in other animals. Our long term goal is to examine the utility of BcfA to generate effective immunity against other bacterial and viral pathogens.
3. Bacterial biofilms.
Biofilms are highly structured communities of cells that are encased in a self-produced polymeric organic matrix and are increasingly recognized as important contributors to chronic or persistent diseases. We hypothesize that the prevalent nasopharyngeal carriage of Bordetella pertussis in adults and adolescents represents the biofilm state. The preliminary and published results with B. pertussis biofilms in mice strongly implicate this lifestyle in humans. We are examining the role of Bordetella factors in biofilm development in vitro and in animals. We are also investigating the contribution of the host innate and adaptive immunity in the progression and development of biofilms.