Biomedical Sciences Graduate Program | University of California, San Francisco

David Erle, MD
Immunopathogenesis of Asthma; Genomics of Disease

Selected Publications | Complete Publications

phone	(415)-514-4370
email	David.Erle@ucsf.edu
additional websites	Immunology Graduate Program Pulmonary & Critical Care Division Shared Microarray Core Facility
secondary research affiliation	Tissue/Organ Biology & Endocrinology

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 and has led to the identification of a molecule that plays a key role in producing a functional mucosal barrier.

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 are also developing a new high-throughput assay for functional analysis of 3’ UTR and miRNA function. 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.

Selected Publications

Kuperman DA, Huang XZ, Koth LL, 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. Nat Med, 8:885-9, 2002.

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 116:305-311, 2005.

Kuperman DA, Huang X, Nguyenvu L, Hölscher C, Brombacher F, Erle DJ. IL-4 receptor signaling in Clara cells is required for allergen-induced mucus production. J Immunol 175:3746-3752, 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 172:1383-92, 2005.

Zhen G, Park SW, Nguyenvu LT, Rodriguez MW, Barbeau R, Paquet AC, Erle DJ. Interleukin-13 and EGF receptor have critical but distinct roles in epithelial cell mucin production. Am J Respir Cell Mol Biol 36(2):244-53, 2007.

Lewis CC, Yang JYH, Huang X, Banerjee SK, Blackburn MR, Baluk P, McDonald DM, Blackwell TS, Nagabhushanam V, Peters W, Voehringer D, Erle DJ. Disease-specific gene expression profiling in multiple models of lung disease. Am J Respir Crit Care Med, 177:376-87, 2008.

Nakagami Y, Favoreto S, Zhen G, Park S-W, Nguyenvu LT, Kuperman DA, Dolganov GM, Huang X, Boushey HA, Avila PC, Erle DJ. The epithelial anion transporter pendrin is induced by allergy and rhinovirus infection, regulates airway surface liquid, and increases airway reactivity and inflammation in an asthma model. J Immunol 2008, in press.

information last updated July 2008