Research Interests

We are currently investigating:

1. Drug-induced hearing loss (ototoxicity), which can ultimately cause the death of sensory hair cells in the inner ear.

a) Drugs that prevent hair cell death following ototoxic drug treatment will avert drug-induced hearing loss.

2. The functional anatomy of hair cells and supporting cells in the inner ear.
3. In addition, the Steyger lab is dedicated to

a) Teaching medical and neuroscience graduate students.

b) Public outreach.

c) Education of health care professionals about the mental health effects of hearing loss.

Click here to view Images of recent studies.
Functional anatomy of the hair cell

Cartoon of a generalized sensory hair cell and a supporting cell in the inner ear.

Vertebrates detect sound, gravity, vibration and motion via specialized hair cells within their inner ear.  Hair cells (HC) have an apical hair-like bundle of many stereocilia and a single kinocilium, which is mechanically deflected by sound pressure waves, gravity, vibrations, or motion.  Inner ear sensory epithelia have a specific cytoarchitectural organization, in that each hair cell is separated from its neighbour by supporting cells (SC).  Each cell type has a specific organization  and expresses a variety of cytoskeletal proteins.The image at left shows in cartoon form the layout of the cytoskeletal structures within the hair cells  and supporting cells of the inner ear.

To conduct our research, we utilize electron microscopy and confocal imaging to view 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 techniques are employed to confirm the activation of relevant signal transduction pathways within cells, or the specificity of antibodies used for immunocytochemistry.

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. But, 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, and then prevent the cellular mechanisms that initiate ototoxic drug-induced hair cell death, and allow clinicians to use aminoglycosides without serious side effects.

We have developed confocal microscopy techniques to document the cellular responses of live hair cells to ototoxic drugs. 
Gentamicin, an aminoglycoside, and forskolin are two unrelated ototoxic drugs that induce mitochondrial depolarization, and sustained increases in intracellular calcium levels, which are powerful triggers for activating cell death pathways. These common cellular responses suggest that unrelated ototoxic drugs trigger common pathways leading to hair cell death. Therefore, we will use in vitro confocal microscopy of fluorescent probes in living hair cells to:

(1) Identify the acute effects of ototoxic drugs in hair cells and supporting cells, and determine if gentamicin and forskolin trigger similar or differing hair cell responses 
(2) Determine if inhibitors of intracellular calcium increases prevent activation of hair cell death pathways
(3) Determine if cytoskeletal mechanisms actively extrude dying hair cells, since the cellular mechanisms of hair cell extrusion are not known.

These confocal microscopy studies of cellular responses of live hair cells ototoxic drugs provide a direct link between the molecular and biochemical studies of ototoxic drugs and the morphological analysis of fixed tissues after drug treatment. This knowledge will significantly advance development of clinical strategies to rescue hair cells from drug-induced cell death, and preserve inner ear function during this critical pharmaceutical therapy.

If you have questions regarding our research, email Peter Steyger.

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