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 Xi'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.
Honors & Awards
2016 Lifetime Achievement Award, Department of Otolaryngology, University of Michigan Medical School
2012 Endowment for Basic Science Teaching Award in Biological Chemistry, University of Michigan Medical School
2011 League of Research Excellence, University of Michigan Medical School
2008 Elected Fellow of the American Association for the Advancement of Science
2007 Foreign Corresponding Member, Cátedra Extraordinaria Innovación Y Salud, Universidad Complutense, Madrid, Spain
2006-2007 Visiting Scholar, University of Washington, Seattle
2005 Honorary Diploma for Outstanding Achievements, Polish Otolaryngological Society
2003 Certificate of Appreciation for promoting equal opportunities for people with disabilities, Council for Disability Concerns, University of Michigan
1996 Honorary Affiliate, Asociación Española de Audiología Experimental
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
1993 Guest Professor, University of Tübingen, Germany
1992 Citation for the Promotion of Hearing-impaired Students in Prof Work Experiences, Nat'l Capital Assoc for Coop Education, Washington DC
1989 Distinguished Faculty Achievement Award, University of Michigan
1984-1991 Senator Jacob Javits Neuroscience Investigator Award, National Institutes of Health, NINCDS
1979-1980 Fogarty Senior International Fellow
Auditory metabolomics, an approach to identify acute molecular effects of noise trauma.
Ji L, Lee HJ, Wan G, Wang GP, Zhang L, Sajjakulnukit P, Schacht J, Lyssiotis CA, Corfas G.
Sci Rep. 2019; 9: 9273.
Assessing ototoxicity due to chronic lead and cadmium intake with and without noise exposure in the mature mouse.
Carlson K, Schacht J, Neitzel RL.
J Toxicol Environ Health A. 2018; 81: 1041-57.
Mutant MRPS5 affects mitoribosomal accuracy and confers stress-related behavioral alterations.
Akbergenov R, Duscha S, Fritz AK, Juskeviciene R, Oishi N, Schmitt K, Shcherbakov D, Teo Y, Boukari H, Freihofer P, Isnard-Petit P, Oettinghaus B, Frank S, Thiam K, Rehrauer H, Westhof E, Schacht J, Eckert A, Wolfer D, Böttger EC.
EMBO Rep. 2018; 19: e46193.
Effects of the 1- N-(4-Amino-2 S-hydroxybutyryl) and 6'- N-(2-Hydroxyethyl) Substituents on Ribosomal Selectivity, Cochleotoxicity, and Antibacterial Activity in the Sisomicin Class of Aminoglycoside Antibiotics.
Sonousi A, Sarpe VA, Brilkova M, Schacht J, Vasella A, Böttger EC, Crich D.
ACS Infect Dis. 2018; 4: 1114-20.
Histone Deacetylase Inhibitors Are Protective in Acute but Not in Chronic Models of Ototoxicity.
Yang CH, Liu Z, Dong D, Schacht J, Arya D, Sha SH.
Front Cell Neurosci. 2017; 11: 315.
Emerging therapeutic interventions against noise-induced hearing loss.
Sha SH, Schacht J.
Expert Opin Investig Drugs. 2017; 26: 85-96.
Vestibular dysfunction in the adult CBA/CaJ mouse after lead and cadmium treatment.
Klimpel KE, Lee MY, King WM, Raphael Y, Schacht J, Neitzel RL.
Environ Toxicol. 2017; 32: 869-76.
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