Research is focused on eosinophil biology and immunological mechanisms of chronic airway inflammation. Ongoing studies include: 1.) elucidating the roles of adhesion molecules, Fc receptors, G protein-coupled receptors in activation and mediator release by eosinophils; 2.) characterizing the innate immune functions of eosinophils and airway epithelial cells; 3.) dissecting the mechanisms of chronic airway inflammation and its outcomes by using murine models and by analyzing the specimens obtained from patients with diseases; and, 4.) elucidation of the immunological mechanisms of diseases, such as bronchial asthma and chronic sinusitis, and development of novel therapeutic approaches for the patients.

A number of recent studies indicate that immunological processes play important roles in the pathophysiology of chronic airway diseases, such as bronchial asthma and chronic sinusitis, and that eosinophils (a type of white blood cells) are one of the major effector cells in these disease processes. Furthermore, eosinophils are likely involved in the mechanisms of other chronic diseases, such as inflammatory bowel disease, as well as in host defense on the mucosal surface.

Our laboratory's goals are to better understand the immunobiology of eosinophilic leukocytes and to elucidate the immunological mechanisms of allergic and chronic airway disorders with the ultimate goals being identification of novel ways to treat patients with these diseases. To this end, a variety of studies are currently ongoing in our laboratory.

The first project focuses on the dissection of the cellular biological mechanisms of eosinophil activation. We found that a number of biological molecules, such as immunoglobulins, cytokines, and lipid mediators, induce eosinophil activation and production of inflammatory mediators by this cell type. Importantly, adhesion molecules, particularly the beta2 integrins, are critically involved in eosinophil activation induced by various classes of secretagogues. Furthermore, these molecules play important roles in recruitment of eosinophils into the sites of inflammation. Therefore, we are characterizing the regulatory mechanisms and functions of eosinophil integrins in comparison to those on neutrophils and are elucidating the roles of these molecules in eosinophilic inflammation using several in vitro systems and in vivo models of allergic inflammation.

The second project is the analysis of the innate immune functions of eosinophils and airway epithelial cells. We are currently focusing on the interaction of these cell types with enzymatic microbial products, such as protease and glycosidase, because these molecules are likely produced at the sites of bacterial infection and fungus colonization. We are evaluating which receptors on eosinophils and airway epithelial cells are used to recognize these enzymes, what are the downstream signaling pathways after receptor activation, and what are the functional outcomes.

The third project examines the pathophysiologic mechanisms of allergic and chronic airway disorders, such as bronchial asthma, chronic sinusitis, and COPD, in humans. We phenotype the inflammatory mediators, such as cytokines, chemokines and immunoglobulins, involved in patients with diseases, characterize the nature of inflammatory cells (e.g. lymphocytes, eosinophils, natural killer cells, dendritic cells), and seek to elucidate how exposure to the etiologic agents (e.g. antigen and microbial products) results in pathologic and physiologic changes of the patients. Several animal models, such as allergen-challenged animals and transgenic and gene knockout mice, are also used to investigate how pharmacologic or immunologic intervention would affect the disease process.

Finally, the fourth project focuses on the hypersensitivity responses of patients with asthma and chronic sinusitis to non-pathologic microorganisms such as environmental fungi. Strong collaboration is established with the Department of Medicine, the Department of Immunology, the Department of Pediatrics and Adolescent Medicine, and the Department of Otorhinolaryngology to address the disease mechanisms and patient treatment.