A major area of interest focuses on the effects of T cell cytokines on resident airway cells. Our central hypothesis is that the key pathologic and physiologic abnormalities characteristic of asthma result from the effects of IL-13 and other Th2 cell cytokines on airway epithelial cells, fibroblasts, and smooth muscle cells. We are particularly interested in dissecting the contributions of specific airway cell types to in vivo pathology. Using transgenic mice developed in the lab, we have shown that IL-13 acts directly on airway epithelial cells to produce two key abnormalities characteristic of asthma: mucus metaplasia and airway hyperreactivity (exaggerated airway narrowing in response to bronchoconstrictors). Ongoing work focuses on identifying the molecular mechanisms responsible for these important responses.

Another major focus is on the use of functional genomic tools, especially DNA microarrays, for studying disease pathogenesis. Members of the group are involved in producing arrays, performing array experiments, and developing and implementing methods for data analysis. We collaborate with many other investigators to study a wide range of problems relevant to lung disease and other diseases. More information about the array facilities is available at http://arrays.ucsf.edu