Research Focus

The major goal of Dr. Barrett's research is to understand the underlying cellular and molecular mechanisms mediating the genetic and environmental factors that contribute to the development and exacerbation of asthma. Additionally, this laboratory is focused on utilizing different animal models of allergy/asthma to test and develop new drugs/therapies for the treatment of allergies/asthma. Three areas of research that are directed toward these goals include the contribution of ultrafine particles (air pollutants) to the development and exacerbation of asthma, the maternal influence in asthma, and the development of an asthma vaccine.

Effects of Inhaled Pollutants on Asthma Epidemiological studies show that hospital admissions for asthma are positively associated with the concentrations of particulate matter (PM) in the air. However, experimental data are limited to support or contradict the possibility that the inhalation of low concentrations of ultrafine PM increases asthma attacks. Immune and inflammatory cells localized to the lungs of asthmatics respond to inhaled allergens with the production and release of inflammatory mediators that play central roles in asthma attacks. Although the inhalation of allergens usually stimulates the release of these inflammatory mediators, exposure to ultrafine particles may also trigger their release in the lungs of allergic individuals. We are currently performing studies to address two hypotheses: inhaled ultrafine particles trigger asthma attacks (1) directly by stimulating the release of allergic response mediators in the lungs of asthmatics, or (2) indirectly by decreasing the concentration of inhaled allergen necessary to cause asthma attacks.

Maternal Influence in Asthma Genetic predisposition for the development of atopy and exposure to high levels of allergen during early childhood have been implicated as the major determining factors for the development of allergic disease. However, increasing evidence suggests that the mother plays an important role in influencing development of fetal and infant immune responses to allergen during gestation. We are testing the hypothesis that elevated levels of maternal antibodies specific for allergen during pregnancy are a risk factor for the development of childhood asthma. In addition, we are testing the hypothesis that exposure of an allergic mother to allergen during pregnancy will predispose the fetus to develop an allergic response to allergen following birth. We are currently defining a murine and canine model to directly test these hypotheses. If, as we hypothesize, the maternal environment is critical in the development of childhood asthma, further studies will examine which maternal/placental/fetal cells are important in mediating the development of the fetal immune response. Ultimately, understanding the maternal component of the risk for developing childhood asthma could lead to new treatment and prevention strategies.

Asthma Vaccine Allergic asthma is characterized by a Th2-mediated immune response to allergen. Several lines of evidence suggest that Th1- (instead of Th2-) like infections during childhood may be protective against the development of allergic disease. A novel approach to preventing allergic disease is to induce a Th1 immune response, thereby preventing a Th2 response. Toll-like receptor (TLR) agonists are highly effective Th1-like vaccine adjuvants and have been successfully used to prevent the sensitization of mice to a Th2 allergen. We are in the process of characterizing the efficacy of various formulations of TLR agonists to prevent or reverse allergic asthma in a canine model of asthma.

CONTACT INFORMATION

Lovelace Respiratory Research Institute
2425 Ridgecrest Dr., SE
Albuquerque, NM 87108

Affiliations

• American Thoracic Society
• Society of Toxicology

Current Projects in the Lab

• Effects of Inhaled Pollutants on Asthma
• The Maternal Influence in Asthma
• Asthma Vaccine