Basic Research

The Department has a variety of ongoing basic science research projects including gene discovery in acoustic neuroma, inner ear hair cell regeneration, molecular basis of vestibular efferent function, molecular genetics of hearing disorders, cell biology of otitis media, molecular characterization of laryngeal papillomas, and gene expression in the cochlear nuclei. The following are basic research projects currently being developed. Each includes a title, primary investigator, and a brief description.

Basic Research Projects

"Molecular Basis of Vestibular Efferent Function"
           P. Ashley Wackym, MD, John C. Koss Professor and Chairman

The management of patients with vertigo and imbalance constitutes a major problem in medicine today. Given the prevalence and debilitating effects of neuro-otologic disorders, there is a great need for a wider and more systematic approach to the solutions of these problems.

This project seeks to 1.) determine the ultrastructural organization of neuro-transmitters and modulators and their receptors detected in the vestibular end-organs; 2.) characterize the genes subserving the efferent/afferent interaction in the rat and human vestibular end-organs and primary afferent ganglia; 3.) determine the anatomic distributions of transcripts expressed by these genes.

"Opioid Regulation of cAMP in the Vestibular Epithelia" 
          Paul Popper, PhD

During their lifetime a significant number of the US population will suffer a balance disorder of vestibular origin. Given the prevalence and the human and material cost associated with loss of balance control, it is important to understand the molecular organization of the vestibular system to develop novel strategies for the management of these disorders.

An incompletely understood aspect of the vestibular system is the role of the wealth of neuroactive substances in the vestibular epithelia. The focus of this project is to study signaling pathways of one class of neuromodulators in the vestibular periphery, opioid peptides. Namely to determine 1.) the effects of opioid receptor activation on cAMP (a molecule involved in opioid signaling) levels in the vestibular epithelia and 2.) the distribution of opioid receptors and cAMP synthesizing enzymes in the vestibular epithelia.

"Middle Ear Epithelial Response to Cytokine"   
          Joseph Kerschner, MD

The most common diagnosis in pediatric patients who visit physicians for illness in the United States is otitis media. This study investigates a more thorough understanding of this disease process. Cultured middle ear cells exposed to inflammatory cytokines are used to investigate 1) changes induced in mucoglycoprotein production; 2) changes induced in mucin gene expression; and 3) post-receptor signal transduction pathways related to cytokine stimulation.

"Differential Gene Expression in the Cochlear Nucleus"
          David Friedland MD, PhD

This study focuses on the molecular mechanisms of information processing in the auditory system. The first step of this process has been to construct Serial Analysis of Gene Expression (SAGE) libraries from each of the three sections of the Rattus norvegicus cochlear nucleus. This information will provide a "snapshot" of the genes expressed (the transcriptome) in each of the three sections, leading to a greater genomic understanding of the anatomic and physiologic functions of the distinct sections.

The hypothesis is that the gene expression of the cochlear nucleus can be correlated with the histologically defined classes of cells (specifically, profile multipolar cells) and can provide an objective means of categorizing auditory neurons.

"Differential Gene Expression in Vestibular Schwannoma" 
          Joseph Cioffi, PhD

Bilateral vestibular schwannoma (acoustic neuroma) occurs in greater than 90% of patients diagnosed with neurofibromatosis type 2, an autosomal dominant genetic disorder. Despite their common cellular origin, vestibular schwannomas can exhibit wide differences in growth rates, degree of vascularity, and cellularity. Left untreated, these tumors can become life threatening.

The most common method of treatment is microsurgical removal which is an expensive, risky, and complicated procedure. This project examines global gene expression patterns in phenotypically distinct vestibular schwannomas.

Techniques such as serial analysis of gene expression (SAGE), microarrays, real-time and reverse transcriptase PCR, and in situ hybridization are principally used to characterize gene expression. Bioinformatics and other routine molecular biology methodologies are also employed.

The overall goals of this research are to correlate specific patterns of gene expression with tumor morphology and growth, and identify unique markers which may serve as valuable prognostic indicators or therapeutic targets.