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Lin_J

Research Abstracts Online
January 2009 - March 2010

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University of Minnesota Twin Cities
Medical School
Department of Otolaryngology

PI: Jizhen Lin

Pathogenesis of Mucous Cell Metaplasia in Pneumococcal Otitis Media

Chronic otitis media with effusion, also known as chronic secretory otitis media (CSOM), is a common otological disease that endangers hearing, leading to communicative disorders in humans. Although aggressive medical approaches have been applied and billions of dollars spent annually, CSOM remains a significant clinical problem. The development of this disease involves bacterial infection in the middle ear cavity and dysfunction of the Eustachian tube. This project’s goal is to characterize the genes involved in this process using cDNA microarrays. It is expected that some previously unrecognized genes involved in these two events will be discovered with this approach. Middle ear effusion of CSOM is rich in glycoprotein(s). Perceivably, the synthesis and secretion of glycoprotein(s) play an important role in this disease. Recent studies in our laboratory of middle ear effusion of CSOM in rats have revealed a glycoprotein with a unique profile of amino acids and carbohydrates. Its composition is characterized by high residues of asparagine and glutamic acid on its backbone polypeptides, as well as residues of mannose and sialic acid on its carbohydrate coat, suggestive of a highly N-glycosylated sialoglycoprotein. The identity and biologic functions of this glycoprotein, however, are unknown. The researcher is therefore cloning and characterizing this glycoprotein using molecular expression techniques. Molecular cloning of this glycoprotein is a first but important step in gaining insight into the molecular mechanism of its metabolism in CSOM and in identifying factors that modulate its synthesis and secretion in the middle ear cleft. Understanding of the regulatory mechanism of this glycoprotein in the middle ear would provide the foundation for development of pharmacological means to intervene in the hypersecretion of this glycoprotein. The long-term goal of this research is to unravel the molecular mechanism of development of CSOM and thus develop innovative treatment strategies through biochemical, immunological, and pharmacological approaches, based on the understanding of the molecular mechanism of this disease.