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

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

Chief
Otolaryngology Branch

Chief
Molecular Biology and Genetics Section
Otolaryngology Branch

NIDCD/NIH
5 Research Court, 1A-13
Rockville, MD 20850
Phone: (301) 402-2829
Fax: (301) 402-7580
E-mail: griffita@nidcd.nih.gov

Dr. Griffith received M.D. and Ph.D. degrees from Yale University.  He completed an Otolaryngology-Head and Neck Surgery residency at the University of Michigan, where he also received fellowship training in the laboratory of Dr. Miriam Meisler in the Department of Human Genetics.

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Otolaryngology Branch

Dr. Griffith and Anne Madeo examine a CT scan.

Dr. Griffith examines a CT scan

Basic molecular biology and genetic research is carried out in the Molecular Biology and Genetics Section. 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.

Ms. Julie Muskett is the Genetic Counselor for the NIDCD. Her responsibilities include coordinating clinical research protocols in the Otolaryngology Branch and the Laboratory of Molecular Genetics, and genetic counseling of subjects participating in NIDCD research studies.

Subjects Needed for Research Studies

The Otolaryngology Branch is seeking research subjects from families to participate in research studies in the following areas:

Information for Patients

Information on hearing loss associated with enlargement of the vestibular aqueduct, Pendred syndrome, and the PDS/SLC26A4 gene can be found on our EVA information pages.

MRI images of the right temporal bone.

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.

Personnel

Julie Muskett, Genetics Counselor (Send e-mail)

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Molecular Biology and Genetics Section

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.

Schematic illustration of the mammalian auditory system (from Griffith and Friedman, Nature Genetics, 1999). View larger image.

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.

Current Areas of Interest

We identified a novel gene, TMC1, which underlies dominant DFNA36 and recessive DFNB7/B11 deafness in humans. Dominant and recessive mutations in the mouse Tmc1 gene underlie deafness in the Beethoven (Bth) and deafness (dn) mouse mutants, respectively, which exhibit rapid degeneration of the neurosensory hair cells of the cochleae. TMC1 protein has no sequence similarities to proteins or domains of known function, but has six transmembrane domains whose topologic organization suggests a role as an ion channel or transporter. There are seven other members of the mammalian TMC gene family, and we are using mutant mouse models to identify the function(s) of Tmc1 and these other Tmc genes. TMC1 and TMC2 are functionally redundant proteins that are required for mechanotransduction at the tips of stereocilia of mouse inner ear hair cells. TMC1 and TMC2 may thus be components of the mechanotransduction channel, or required for its structure, function or development. We are using a variety of approaches to distinguish among these possibilities.
Illustration of the TMC1 gene

Schematic illustration of TMC1 showing predicted transmembrane topology and human and mouse mutations causing deafness. View larger image.

A second 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.

Lab Personnel

Kiyoto Kurima, Ph.D., Staff Scientist (Send e-mail | View photo)
Parna Chattaraj, M.S., Biologist (Send e-mail)
Hiroshi Nakanishi, M.D., Ph.D., Visiting Fellow (Send e-mail)
Taku Ito, M.D., Ph.D.,Visiting Fellow (Send e-mail)
Ayako Nishio, M.D., Visiting Fellow (Send e-mail)

Lab Photos

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Selected Publications

2011

2010

2009

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