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
1979-1980 Fogarty Senior International Fellow
1984-1991 Senator Jacob Javits Neuroscience Investigator Award, National Institutes of Health, NINCDS
1989 Distinguished Faculty Achievement Award, University of Michigan
1992 Citation for the Promotion of Hearing-impaired Students in Prof Work Experiences, Nat'l Capital Assoc for Coop Education, Washington DC
1993 Guest Professor, U of Tabingen, Germany
1994 Chercheur Ãtranger, Univ of Montpellier, France Laboratoire de Neurobiologie de l'Audition, Ins't Nat'l de la santé et de la recher médicale
1996 Honorary Affiliate, Asociación Española de Audiología Experimental
2003 Certificate of Appreciation for promoting equal opportunities for people with disabilities, Council for Disability Concerns, Univ of Mich
2005 Honorary Diploma for Outstanding Achievements, Polish Otolaryngological Society
2006-2007 Visiting Scholar, U of Washington, Seattle WA
2007 Foreign Corresponding Member, Cátedra Extraordinaria Innovación Y Salud, Universidad Complutense, Madrid, Spain
2008 Elected Fellow of the American Association for the Advancement of Science
2011 League of Research Excellence, University of Michigan Medical School
2012 Endowment for Basic Science Teaching Award in Biological Chemistry, University of Michigan Medical School
2016 Lifetime Achievement Award, Department of Otolaryngology, University
Shulman, E., Belakhov, V., Wei, G., Kendall, A., Meyron-Holtz, E.G., Ben-Shachar, D., Schacht, J. and Baasov, T. Decreased selectivity toward mitochondrial versus cytoplasmic ribosome confers decreased ototoxicity of designer aminoglycosides. J. Biol. Chem. 289:2318-2330, 2014. doi: 10.1074/jbc.M113.533588. Epub 2013 Dec 3. PMCID: PMC3900975
Oishi, N., Kendall, A, and Schacht, J. Metformin protects against gentamicin-induced hair cell death in vitro but not ototoxicity in vivo. Neurosci. Lett. 583:65-69, 2014. doi: 10.1016/j.neulet.2014.09.028. PMICD: PMC4253637
Duscha, S., Boukari, H., Shcherbakov, D., Salian, S., Silva, S., Kendall, A., Kato, T., Akbergenov, R., Perez-Fernandez, D., Bernet, B., Vaddi, S., Thommes, P., Schacht, J., Crich, D., Vasella, A., Böttger, E.C. Identification and evaluation of improved 4’-O-(alkyl) 2-deoxystreptamines as next-generation aminoglycoside antibiotics. mBio 5:e01827-14, 2014. doi: 10.1128/mBio.01827-14. PMCID: PMC4196235
Kendall, A. and Schacht, J. Disparities in auditory physiology and pathology between C57BL/6J and C57BL/6N substrains. Hear. Res. 318:18-22, 2014. doi: 10.1016/j.heares.2014.10.005. PMCID: PMC4258454
Altschuler, R.A., Dolan, D.F., Halsey, K., Kanicki, A., Deng, N., Martin, C., Eberle, J., Kohrman, D.C., Miller, R.A., and Schacht, J. Age-related changes in auditory nerve–inner hair cell connections, hair cell numbers, auditory brain stem response and gap detection in UM-HET4 mice. Neuroscience 292:22-33, 2015. doi: 10.1016/j.neuroscience.2015.01.068. PMCID: PMC4511166
Oishi, N., Duscha, S., Boukari, H., Meyer, M., Xie, J., Wei, G., Schrepfer, T., Roschitzki, B., Boettger, E.C. and Schacht, J. XBP1 mitigates aminoglycoside-induced endoplasmic reticulum stress and neuronal cell death. Cell Death Dis. 6:e1763, 2015. doi: 10.1038/cddis.2015.108. PMCID: PMC4669688
Shalev, M., Rozenberg, H., Smolkin, B., Nasereddin, A., Kopelyanskiy, D., Belakhov, V., Schrepfer, T., Schacht, J., Jaffe, C.L., Adir, N. and Baasov, T. Structural basis for selective targeting of leishmanial ribosomes: Aminoglycoside derivatives as promising therapeutics. Nucl Acids Res. 43:8601-8613, 2015. doi:10.1093/nar/gkv821. PMCID: PMC4787808
Yang, C.-H., Schrepfer, T. and Schacht, J. Age-related hearing impairment and the triad of acquired hearing loss. Front. Cell. Neurosci. 9:276, 2015. doi: 10.3389/fncel.2015.00276. PMCID: PMC4515558
Sha, S-H., Talaska, A.E. and Schacht, J. Age-related changes in the auditory system. In: Hazzard’s Geriatric Medicine and Gerontology, 7th edition (Halter, J.B., Ouslander, J.G., Studenski, S., High K.P., Asthana, S., Ritchie, C. and Supiano, M., eds.), McGraw-Hill Co., New York, pp. 577-589, 2017.
Sha, S-H. and Schacht, J. Emerging therapeutic interventions against noise-induced hearing loss. Exp. Op. Investig. Drugs 26:85-96, 2017. doi: 10.1080/13543784.2017.1269171. PMID: 27918210
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
For a complete list of this person’s PubMed publications, click HERE