Director of Research
Department of Otolaryngology-HNS
Case Western Reserve University
The focus of my lab is to understand the genetic basis of inner ear development, hearing and deafness, using mouse models. Since many deafness disorders in humans are associated with degeneration of the inner ear neuroepithelia, we are interested in identifying and studying mammalian genes that are involved in the development and maintenance of the neuroepithelium of the inner ear. The molecular analysis of hearing loss mutations in the mouse is an ideal way of gaining access to such genes. Current work in the lab is focused on one mouse mutation called Ames waltzer (av). The mouse av is a recessive mutation, which causes deafness and circling behavior (vestibular dysfunction) associated degeneration of hair cells in the postnatal inner ear. The gene that harbors the av mutation was identified as a protocadherin, Pcdh15 (Nat Genet. 27: 99, 2001; Hum Mol Genet. 10:1709, 2001; Hear Res. 148:181, 2000; Genetics 152:1691, 1999). Experiments are underway to understand the role of Pcdh15 in inner ear development.
Genetic, noise and drug induced loss of hair cells in the mouse and human cochlea leads to permanent hearing loss because these hair cells are not replaced. Vestibular epithelia from adult mouse show limited regenerative ability following injury, which is thought to be due to the presence of vestibular epithelial stem cells. Lack of regeneration of cochlear hair cells may be due to reduced number and/or loss of regenerative ability of stem cells in the adult cochlea. In collaboration with Robert Miller’s lab, we are looking to demonstrate the presence of cochlear stem cells in postnatal mouse organ of Corti using stem cell culture techniques and determine the conditions that would be permit the differentiation of cochlear stem cells to hair cells. These cochlear stem cells could then be transplanted into the postnatal cochlea of deaf mouse mutants, such as the av mouse, to determine if the lost hair cells could be restored.