Areas of Interest
Our studies focus on signaling pathways in the auditory system and mechanisms leading to deafness.
We are investigating signaling pathways that control the homeostasis and survival of the auditory sensory cells, for example those mediated by phospoinositide-3-kinase, Akt, or NF-kB. Small Rho GTPases also play a crucial role in the control of the actin cytoskeleton which is essential in the maintenance of the structural integrity of the auditory organ. Other pathways of interest for us are those that control cell death via apoptosis or necrosis. These studies of cell signaling mechanisms strongly overlap with our studies on drug- and noise-induced as well as age-related hearing loss since we are frequently using such models as investigative tools.
However, our interest in various forms of hearing loss also extends to questions of the molecular mechanisms of the underlying pathologies with the ultimate aim of designing preventive treatments. Aminoglycoside antibiotics, for example, are a leading cause of preventable hearing loss worldwide. Having determined oxidant stress as a trigger of cell death in sensory cells exposed to these drugs, we could reduce hearing loss in animal models by the co-administration of antioxidants. Together with colleagues in Xiâ-an, China, we then took these preventive treatments to clinical trials which showed a dramatic 75% reduction in risk of hearing loss in patients receiving aminoglycosides.
The study was published in the New England Journal of Medicine and you can check out this University of Michigan press release.
Honors & Awards
1993 Guest Professor, U of Tabingen, Germany
1994 Chercheur Ãtranger, University of Montpellier, France Laboratoire de Neurobiologie de l'Audition, Institut National de la SantÃ© et de la Recherche MÃ©dicale
1996 Honorary Affiliate AsociaciÃ³n EspaÃ±ola de AudiologÃa Experimental
2003 Certificate of Appreciation for promoting equal opportunities for people with disabilities Council for Disability Concerns, University of Michigan
2005 Honorary Diploma for outstanding achievements Polish Otolaryngological Society
2006-2007 Visiting Scholar, U of Washington, Seattle WA
Jiang, H., Sha, S-H. and Schacht, J. The NF-kB pathway protects cochlear hair cells from aminoglycoside-induced ototoxicity. J. Neurosci. Res. 79:644–651, 2005. doi: 10.1002/jnr.20392
Jiang, H., Sha, S-H., Forge, A. and Schacht, J. Caspase-independent pathways of hair cell death induced by kanamycin in vivo. Cell Death Diff. 13:20-30, 2006. doi: 10.1038/sj.cdd.4401706 PMID: 16021180
Sha, S-H., Qiu, J-H. and Schacht, J. Aspirin to prevent gentamicin-induced hearing loss. New Engl. J. Med. 354:1856-1857, 2006. PMID: 16641409
Jiang, H., Sha S-H. and Schacht, J. Rac/Rho pathway regulates actin depolymerization induced by aminoglycoside antibiotics. J. Neurosci. Res. 83:1544-1551, 2006. doi: 10.1002/jnr.20833 PMID: 16521128
Vicente-Torres, M.A. and Schacht, J. A BAD link to mitochondrial cell death in noise-induced hearing loss. J. Neurosci. Res. 83:1564-1572, 2006. doi: 10.1002/jnr.20832
Jiang, H., Sha, S-H. and Schacht, J. Kanamycin alters cytoplasmic and nuclear phosphoinositide signaling in the organ of Corti in vivo. J. Neurochem.
Jiang, H., Talaska, A.E., Schacht, J. and Sha, S-H. Oxidative imbalance in the aging inner ear. Neurobiol. Aging PMID: 16920227