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 hyperresponsiveness (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 . |
Kuperman D, Huang X, Koth LL, Chang GH, Dolganov GM, Zhu Z, Elias JA, Sheppard D, Erle DJ. Direct effects of interleukin-13 on epithelial cells cause airway hyperreactivity and mucus overproduction, two central features of asthma. Nature Med 8:885-9, 2002.
Koth LL, Rodriguez MW, Bernstein XL, Chan S, Huang X, Charo IF, Rollins BJ, Erle DJ. Aspergillus antigen induces robust Th2 cytokine production, inflammation, airway hyperreactivity and fibrosis in the absence of MCP-1 or CCR2. Respir Res. 15:12, 2004.
Kuperman DA, Lewis CC, Woodruff PG, Rodriguez MW, Yang YH, Dolganov GM, Fahy JV, Erle DJ. Dissecting asthma using focused transgenic modeling and functional genomics. J Allergy Clin Immunol 116:305-11, 2005.
Kuperman DA, Huang X, Nguyenvu L, Holscher C, Brombacher F, Erle DJ. IL-4 receptor signaling in Clara cells is required for allergen-induced mucus production. J Immunol 175:3746-52, 2005.
Woodruff PG, Koth LL, Yang YH, Rodriguez MW, Favoreto S, Dolganov GM, Paquet AC, Erle DJ. A distinctive alveolar macrophage activation state induced by cigarette smoking. Am J Respir Crit Care Med 172:1383-1392, 2005.
information last updated June 2006 |
Biomedical Sciences (BMS) Graduate Program
