Research Overview
Biology of Hair Cell Death
This research program focuses on the mechanisms of hair cell death in the inner ear. Death of sensory hair cells is the underlying cause of the majority of hearing losses and balance disorders. Hair cells die in response to a number of insults, including aging, noise trauma, and exposure to certain therapeutic drugs (including aminoglycoside antibiotics and the anti-cancer drug cis-platin). We now understand that hair cell death in response to most (or all) of these signals is an active process. That is, the cell actually commits "cell suicide" (also called "apoptosis") by making or activating proteins that will destroy it. These proteins include survival factors, anti- and pro-apoptotic members of the bcl-2 family, and a group of cell-death proteases called caspases. The goals of this work are to understand the cascade of cellular and molecular events involved in determining if challenged hair cells survive or die, and eventually to design therapies aimed at preventing hair cell death.
Several approaches are used in the laboratory to examine hair cell respnses to ototoxic events. We are using in vitro preparations of both mouse vestibular hair cells and chick auditory hair cells to examine the specific caspases that are activated during aminoglycoside-induced hair cell apoptosis as well as the effects of inhibitors of caspases on hair cell death. The advantages of the mouse preparation are that it is a mammalian hair cell epithelium and that it allows us examine hair cell death in various transgenic animals expressing mutant forms of genes involved in apoptosis. The advantage of the chick preparation is that it allows us to examine hair cell death in an auditory hair cell epithelium. In addition, we are using hair cells in the lateral line neuromasts of zebrafish to find genes influencing hair cell susceptibility to damaging agents.
Ontogeny of the Vertebrate Sensory Processes
