Faculty
Dr. Su-Hua Sha
Laboratory Director, Molecular Otology and Signal Transduction Laboratory
Email:
Phone: (734) 647-0563
Fax: (734) 764-0014
Accomplishments
- Study of Medicine, Tongji Medical University, Wuhan, China, 1978-1983
- Resident in Otolaryngology, Tongji Medical University, Wuhan, China, 1983-1989
- Physician in Otolaryngology, Tongji Medical University, Wuhan, China, 1989-1991
- Visiting Fellow, Otolaryngology, University of Essen, Essen, Germany, 1992-1994
- Assistant Professor of Otolaryngology, Tongji Medical University, Wuhan, China, 1994-1997
- Postdoctoral Fellow, Kresge Hearing Research Institute, University of Michigan, 1994-1997
- Research Associate, Kresge Hearing Research Institute, 1998-2001
- Research Investigator, Department of Otolaryngology, University of Michigan, 2001-Present
Hobbies
- Travel
- Music
- Tennis
- Dance
Research Projects
My research focuses on redox-regulated signal transduction pathways in noise-induced hearing loss. In addition, I am collaborating extensively with Dr. Schacht�s laboratory on drug-induced hearing loss and presbycusis.
Noise-induced hearing loss
It may be surprising that the auditory system - designed to process acoustic information - is sensitive to intense sound. Today noise-induced hearing loss is a major and increasing problem in industrialized countries stemming both from the work place and from leisure activities. While most of the public is aware of the dangers of factory and machinery noises, gun shots and airplanes, many seem to disregard the dangers to their hearing of techno and disco music and "walkmen" at high volume. Tinnitus (ringing in the ears), temporary elevation in hearing threshold and permanent hearing loss are possible consequences.
Our current work focuses on two topics. One concerns the initial events following noise exposure which may involve the enhanced formation of reactive oxygen species and therefore upset the redox balance of the cell. The second focus is on the resulting signaling pathways, their transcription factors, and the eventual effects on gene expression.
Collaborative projects
Both in vivo and in vitro studies from our laboratory have shown that oxidative stress is a causative factor in aminoglycoside-induced hearing loss. Formation of reactive oxygen species (ROS) by aminoglycosides has been evidenced by redox-active gentamicin-iron-lipid complexes in vitro and by the ability to attenuate ototoxicity in vivo with several antioxidants. The imbalance of the redox-homeostasis of the cells then activates redox-regulated signaling pathways, for example, NF-ϰB signaling. The subunits of NF-ϰB translocate into the nuclei of outer hair cells, protecting them from aminoglycoside-induced ototoxicity. If the noxious stimuli overwhelm the cell's defenses, pathways that regulate cell death predominate, leading to apoptotic or necrotic outer hair cell death. We recently found that caspase-independent cell death pathways play a major roll in chronic aminoglycoside-induced hair cell death.
We are cooperating with our colleagues at the Department of Otolaryngology at Xijing Hospital in Xi'an, China, who are conducting a clinical study supplementing gentamicin treatment with aspirin. The results are published in the New England Journal of Medicine (354:1856-1857, 2006). We are now trying to improve on this protective therapy because aspirin, despite its century-long history as a common drug, can have some adverse effects. It is particularly interesting for us that some Chinese traditional herbal medicines have antioxidant properties and may attenuate some of the ototoxic effects of aminoglycosides. Similar medications are known in other Asian and African countries and would be well accepted by patients there. A combination of Western medication with traditional remedies might be an effective way to help alleviate the problem of drug-induced hearing loss in the developing countries. In parallel, we are pursuing potentially protective drugs and drug combinations that are readily available in industrialized countries where cost of medications is not such a limiting factor.
We have new program project grant studying the mechanism of Presbycusis (age-related hearing loss) together with other groups at the Kresge Hearing Research Institute and the Geriatrics Center at the University of Michigan. My studies involve the determination of free radical formation and cochlear antioxidant defenses as well as redox-sensitive homeostatic signaling pathways which engage protein kinases and phosphatases. Cell death pathways are also part of our effort to understand hair cell death in the aging ear.
