Graduate Training in Neuroscience
University of Washington
Assistant Professor, Department of Otolaryngology-HNS
Mammalian inner ear development: The complex mosaic of cell types comprising the mature mammalian inner ear develops during embryogenesis through a series of cell-cell interactions. My laboratory is interested in how different classes of transcription factors, in particular the LIM and helix-loop-helix (HLH) families, interact to regulate inner ear development. An understanding of these mechanisms in development may provide insight into how to manipulate gene expression in the mature inner ear to regenerate deficient cell types in specific forms of hearing loss.
Gene therapy of inner ear disorders: The specific genetic mutations underlying many different forms of congenital deafness have been identified during the past few years. I have been utilizing an in vitro neonatal mouse organ of Corti culture system to develop means of introducing exogenous genes into cells of the inner ear. In this system, I have been able to induce formation of cells with properties of hair cells by ectopically expressing transcription factor genes. I am continuing these studies to develop non-viral and viral methods directed towards gene therapy of hearing disorders with specific focus on those related to known genetic mutations and hair cell regeneration.
Imaging Analysis of the Inner Ear: There are two fluid compartments in the inner ear: the endolymphatic space and the perilymphatic space. In different forms of hearing loss there are believed to be alterations in the relative sizes of these fluid compartments (Meniere's disease) or of their ionic composition (some forms of presbycusis and congenital hearing loss, sudden hearing loss). None of these models/hypotheses has been verified in humans, in vivo. I am collaborating with members of the University of Washington Department of Radiology to develop more sensitive methods for analyzing the human inner ear using imaging technology.