Oregon Health & Science University
Oregon Hearing Research Center
About the OHRC
Peter Steyger faculty page
Confocal Microscopy at OHRC
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The Steyger Lab:
Functional Anatomy of the Inner Ear and Ototoxicity
The lab is
located in the Oregon Hearing Research Center at the Oregon Health Sciences
University, and comprises Peter Steyger, Ph.D. (principal investigator),
Takatoshi Karasawa Ph.D. (post-doctoral fellow), Qi Wang, M.D., MS (Senior
research assistant) and Zachery Oestreicher, M.S. (confocal microscopy
manager), and Rachel Monfils (high school intern)
Peter Steyger, Ph.D., was selected by Davis Wright Tremaine LLP - one of the largest law firms in the
country - as an
Inventor of the Month for October 2003 in honor of his work in drug-induced hearing loss.
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Contact Information
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Oregon Hearing Research Center
Oregon Health and Science Univaersity
3181 SW Sam Jackson Park Rd.
Portland, OR, 97239-3098
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Voice: 1-503-494-1062
Fax: 1-503-494-5656
email: steygerp@ohsu.edu
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Research Interests
- The functional anatomy of
hair cells and supporting cells in the inner ear.
- Entry of ototoxic drugs into the inner ear
fluids that induce hearing loss (ototoxicity)
- In addition, the Steyger lab
is dedicated to
- Teaching
medical and neuroscience graduate students.
- Public
outreach.
- Education
of health care professionals about the mental health effects of hearing loss.
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Functional anatomy of the hair cell
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Vertebrates
detect sound, gravity, vibration and motion via specialized sensory hair
cells within their inner ear. Hair cells (HC) have an apical hair
bundle of many stereocilia and (sometimes) a single kinocilium. The hair
bundle is mechanically deflected by sound pressure waves, gravity,
vibrations, or motion, mechano-electrically transducing the physical
stimulus into neuro-electric action potentials.
Inner ear sensory
epithelia have a specific cytoarchitectural organization, in that each hair
cell is separated from its neighboring by supporting cells (SC). Each cell
type has a specific organization and expresses a variety of
cytoskeletal proteins. The cartoon (left) shows a generalized layout of the
cytoskeletal structures within the hair cells and supporting cells of
the inner ear.
To conduct our anatomical research, we
utilize electron microscopy and confocal
imaging to view labeled proteins in hair cells from a variety of
vertebrate inner ears These tools allow both high power magnification
and fluorescent imaging to image target organelles, proteins, and
intracellular locations of ototoxic drugs.
In addition, biochemical and molecular
biological techniques are employed to confirm the activation of relevant
signal transduction pathways within cells.
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Ototoxicity
Ototoxicity can ultimately lead to sensory hair cell death, causing hearing
loss and vestibular disorders. Yet clinical use of aminoglycoside
antibiotics is essential against life-threatening bacterial infections,
e.g., meningitis, encephalitis, tuberculosis, and large wound injuries. However,
there are serious ototoxic and nephrotoxic side-effects in 4-14% of all
aminoglycoside prescriptions (4 million annually), leading to mental,
educational, language, and renal difficulties in patients suffering these
side-effects. The overall aim of our studies are to identify the cellular mechanisms that enable
ototoxic drugs to enter sensory hair cells to induce cytotoxicity. The
ultimate goal is to develop co-therapeutics that will allow clinicians to
use aminoglycosides without serious side effects.
We have developed confocal
microscopy and other imaging techniques to document the trans-cellular transport
of ototoxic drugs into the inner ear
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