Auditory Hair Cell Physiology Laboratory

Our laboratory studies the hair cells of the inner ear and the molecular pathways governing their function. Sound waves entering the cochlear from the middle ear cause the organ of Corti to vibrate, stimulating the inner hair cells along the basilar membrane. The inner hair cells then convert this mechanical energy into an electric signal that travels to the brain via the afferent neuronal pathway. The brain also feeds back and regulates this incoming auditory signal through the efferent pathway. The efferent pathway connects to the outer hair cells of the organ of Corti, which fine-tunes the incoming auditory signal. We have predominantly focused upon this efferent pathway and the resulting outer hair cell response and its role in hearing.

 There are currently several projects that we are focused upon involving the efferent auditory system and outer hair cells. Based on results from a protein-protein binding study, we have been looking at the roles of both saposins and synculeins within the inner ear. We are also interested in novel protein function within this system.

 In addition to these studies, we are also interested in the mechanism causing hearing loss as a consequence of exposure to ototoxic drugs. In a collaboration with the laboratory of Dr. Kathy Giacomini at UCSF, in the Department of Biopharmaceutical Sciences, we have been studying the role of copper transports in the inner ear, and how they contribute to platinum ototoxicity. It is anticipated this collaboration will lead to the development of safer chemotherapeutic compounds without the risk of ototoxicity. It is also hoped that this work will shed new, important light on the underlying role of copper transporters in hair cell function.

 In an important collaboration with the lab of Dr. Tamara Alliston in the UCSF Department of orthopedic surgery, we have been studying the physiology of otic capsule bone, the bone that houses the cochlea, and is considered the ‘hardest bone in the body.’ Not only will such a model of bone shed important light on bone physiology in general, but will also lead to a greater understanding of how the material properties of bone contribute to hearing mechanism.

 The techniques employed in our lab are highly specialized. In addition to such molecular approaches as yeast-two-hybrid protein-protein interaction assays, we are involved in studying a variety of transgenic mice to understand molecular echanisms of hearing loss. Additionally, we routinely employ standard molecular techniques (RT-PCR, QPCR), immunohistochemistry and immunofluorescence and western blot of microdissected inner ear tissues and have the ability to isolate individual hair cells to perform highly specific molecular studies on their function. We also regularly perform light and electron microscopy of the inner ear in mammalian tissues. We routinely perform auditory physiology on animals to help us understand the structural consequences of our molecular interventions, including acoustic brainstem response testing, compound action potential testing, distortion product otoacoustic emissions testing, and also have the ability to specifically study the efferent pathways using contralateral suppression of otoacoustic emissions. These approaches help correlate structure to function in the auditory periphery of a normal and pathological ear and understand the mechanism and\or function of a protein in the normal ear.