Developmental neurobiology; molecular neurobiology; studies of developing neuronal cells and synapses; cytochrome oxidase; auditory system; gene arrays; deafness.
My research group uses modern molecular biological, molecular genetic and cell biological techniques to study both the development of the ear and the response of the inner ear to noise trauma. The inner ear is an important sensory organ that controls both balance and hearing. We are interested in three broad areas.
1. The role of ZIC transcription factors in the embryological development of the inner ear. This project is a collaboration with Dr. Kate Barald, also of the Dept. of Cell and Developmental Biology (CDB). We are studying the effects of chordin, a BMP4 antogonist, on the induction of ZIC genes in mouse otocyst-derived cell lines as they differentiate in culture to a neuronal phenotype. We also have identified genes that are expressed in the otocyst (the embryonic structure that develops into the ear) during early chick development.
2. The effects of noise damage on both the chick and rat inner ear. We use the chick as a model system for these studies because birds (and amphibians) can regenerate the important auditory (sensory) hair cells in the auditory epithelium after noise damage, whereas humans can not. Once we identify genes that are up-regulated following noise damage, we use all the tools of the cell biologist to examine the location of both the mRNA and protein in the normal chick basilar papilla and after noise damage. We are focusing on genes involved in two pathways: actin dynamics and ubiquitin-mediated protein turnover. Understanding the function of these genes is a major challenge. To investigate how the mammalian ear responds to noise overstimulation, we are using gene arrays to identify differentially regulated genes. These studies have led to investigations of several immediate early genes for both transcription factors and cytokines, and are part of a collaborative project with Dr. Richard Altschuler, CDB and KHRI. Damon Fairfield, a CDB graduate student, is investigating the stress response in the rat inner ear after noise damage. He developed molecular assays for stress response transcription factors (HSFs) and proteins (HSPs), which are known to protect other organs against various traumas.
3. The genetics of otosclerosis and other forms of hereditary deafness. There has been an explosion of research on the genetics of deafness during the last 10 years. At least 50 genes have been mapped in humans, and about 20 have been identified to date. Our colleague, Dr Marci Lesperance, a pediatric otolaryngologist studying families with inherited deafness, has identified mutations in the NOGGIN gene in two families with conductive hearing loss due to stapes fixation. and trying to map and identify which genes are involved. In collaboration with Dr. Lesperance, we are beginning to examine the role of noggin in bone and joint formation in the ear.
4. Muscle-specific expression of cytochrome c oxidase. We also have a long-standing interest in the molecular genetics of cytochrome c oxidase (COX)and, in collaboration with Dr. John Kennedy, Univ. of Illinois at Chicago, are examining the effects of electrical stimulation of intact muscle on expression of muscle-specific COX genes.