My research group uses modern molecular biological,
molecular genetic and cell biological techniques to study both the
development of the ear and the response of the inner ear to noise
trauma. The inner ear is an important sensory organ that controls
both balance and hearing. We are interested in three broad areas.
1. The role of ZIC transcription factors in the embryological development
of the inner ear. This project is a collaboration with Dr. Kate
Barald, also of the Dept. of Cell and Developmental Biology (CDB).
We are studying the effects of chordin, a BMP4 antogonist, on the
induction of ZIC genes in mouse otocyst-derived cell lines as they
differentiate in culture to a neuronal phenotype. We also have identified
genes that are expressed in the otocyst (the embryonic structure
that develops into the ear) during early chick development.
2. The effects of noise damage on both the chick and rat inner
ear. We use the chick as a model system for these studies because
birds (and amphibians) can regenerate the important auditory (sensory)
hair cells in the auditory epithelium after noise damage, whereas
humans can not. Once we identify genes that are up-regulated following
noise damage, we use all the tools of the cell biologist to examine
the location of both the mRNA and protein in the normal chick basilar
papilla and after noise damage. We are focusing on genes involved
in two pathways: actin dynamics and ubiquitin-mediated protein turnover.
Understanding the function of these genes is a major challenge.
To investigate how the mammalian ear responds to noise overstimulation,
we are using gene arrays to identify differentially regulated genes.
These studies have led to investigations of several immediate early
genes for both transcription factors and cytokines, and are part
of a collaborative project with Dr. Richard Altschuler, CDB and
KHRI. Damon Fairfield, a CDB graduate student, is investigating
the stress response in the rat inner ear after noise damage. He
developed molecular assays for stress response transcription factors
(HSFs) and proteins (HSPs), which are known to protect other organs
against various traumas.
3. The genetics of otosclerosis and other forms of hereditary deafness.
There has been an explosion of research on the genetics of deafness
during the last 10 years. At least 50 genes have been mapped in
humans, and about 20 have been identified to date. Our colleague,
Dr Marci Lesperance, a pediatric otolaryngologist studying families
with inherited deafness, has identified mutations in the NOGGIN
gene in two families with conductive hearing loss due to stapes
fixation. and trying to map and identify which genes are involved.
In collaboration with Dr. Lesperance, we are beginning to examine
the role of noggin in bone and joint formation in the ear.
4. Muscle-specific expression of cytochrome c oxidase. We also
have a long-standing interest in the molecular genetics of cytochrome
c oxidase (COX)and, in collaboration with Dr. John Kennedy, Univ.
of Illinois at Chicago, are examining the effects of electrical
stimulation of intact muscle on expression of muscle-specific COX
genes.
Representative Publications:
- Oh, S.-H., Adler, S.J., Raphael, Y., and Lomax, M.I.: WDR1
colocalizes with ADF and actin in the normal and noise damaged
chick cochlea. J. Comp. Neurol., in press.
- Cho, Y., T.-W.L. Gong, T. Stover, M. I. Lomax, and R. A. Altschuler.
Gene expression profile of the rat cochlea, cochlear nucleus and
inferior colliculus. JARO, 3:54-67, 2001.
- Gong, T.-W. L., Besirli, C.G., and Lomax, M.I. MACF1 gene structure: a hybrid of plectin and dystrophin. Mammalian
Genome 12:852-861, 2001.
- Lomax, M.I., L. Huang, Y. Cho, T.-W. L. Gong, and R. A. Altschuler.
Differential display and gene arrays to examine auditory plasticity.
Hearing Research, 147:293-302, 2000.
- Greene, C.C., P.M. McMillan, S. E. Barker, P. Kurnool, M.I.
Lomax, M. Burmeister and M.M. Lesperance:. DFNA25, a novel locus
for dominant nonsyndromic hereditary hearing impairment, maps
to 12q21-24. Am J Human Genetics, 68:254-260, 2001.
- Gong TW, Winnicki RS, Kohrman DC, Lomax MI: A
novel mouse kinesin of the UNC-104/KIF1 subfamily encoded by the
Kif1b gene. Gene 239:117-127, 1999.
- Bachman NJ, Wu W, Schmidt TR, Grossman LI, Lomax MI: The
5' region of the COX4 gene contains a novel overlapping gene,
NOC4. Mamm Genome. 10:506-512, 1999.
- Adler HJ, Winnicki RS, Gong TW, Lomax MI: A
gene upregulated in the acoustically damaged chick basilar papilla
encodes a novel WD40 repeat protein. Genomics 56:59-69, 1999
- Grossman LI, Lomax MI: Nuclear
genes for cytochrome c oxidase. Biochim Biophys Acta 1352:174-192,
1997.
- Gong TW, Hegeman AD, Shin JJ, Adler HJ, Raphael Y, Lomax
MI:
Identification of genes expressed after noise exposure in the
chick basilar papilla. Hear Res. 96:20-32, 1996.
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