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Molecular Biology and Genetics Section

Andrew J. Griffith, M.D., Ph.D., Former Chief

In the Otolaryngology Branch, basic molecular biology and genetic research is carried out in the Molecular Biology and Genetics Section. The Audiology Unit research activities include audiological and vestibular assessment of human subjects participating in clinical research protocols of the Otolaryngology Branch, the NIDCD, or other NIH institutes and centers.

Dr. Griffith and Anne Madeo

Dr. Andrew Griffith examines a CT scan.

mammalian auditory system

Illustration: View of the mammalian auditory system showing: cochlea, vestibular apparatus, inner hair cell, scala media, tectorial membrane, outer hair cells, cochlear ganglion, organ of Corti, basilar membrane, and stria vasicularis (from Griffith and Friedman, Nature Genetics, 1999).

Axial T2-weighted fast spin echo MRI images of the right temporal bone showing enlargement of the endolymphatic system (known as EVA) when visualized on CT scans.

Research Statement

Our laboratory identifies and characterizes genes, molecules, and mechanisms underlying hearing and hereditary hearing loss. We use molecular biologic and genetic approaches, human and mouse models, as well as heterologous cell culture expression systems. A variety of techniques—including in situ hybridization, immunohistochemistry, RT-PCR, Western and Northern blotting, and immunoprecipitation—are used to analyze gene and protein expression, function, and interactions. We aim to identify potential therapeutic opportunities in animal models for translation to clinical interventions.

Current Areas of Interest

A major project is the molecular genetic analysis of human hearing loss associated with enlargement of the vestibular aqueduct (EVA). EVA is the most commonly observed inner ear malformation in children with hearing loss. In many cases EVA is associated with mutations in the Pendred syndrome gene PDS/SLC26A4, which encodes an integral membrane protein that is thought to transport or exchange chloride, iodide, bicarbonate, or other bases in the inner ear. Our current projects include the identification of novel genes for EVA in human patients, and the generation and characterization of novel mouse models for EVA. We are using these models to better understand the pathophysiology of hearing loss in EVA and, in the future, explore potential therapeutic agents to prevent, reduce, or reverse hearing loss in EVA.

Another major project is exploring the role of innate immunity in sensorineural hearing loss. Mutations in the NLRP3 gene can cause hearing loss as an isolated trait or as part of a syndrome. The NLRP3 protein, cryopyrin, is an important component of the signaling cascade underlying an innate immune response. Gain-of-function activating mutations of NLRP3 cause auto-inflammation that can affect the inner ear and other organs. We are studying the role of this pathway in hearing loss in mouse models.

Lab Personnel

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