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
Lifetime Achievement Award, Department of Otolaryngology, University of Michigan Medical School, 2016
Endowment for Basic Sciences Teaching Award, University of Michigan Medical School, 2012
League of Research Excellence, University of Michigan Medical School, 2011
Elected Fellow, American Association for the Advancement of Science, 2008
Foreign Corresponding Member, Cátedra Extraordinaria Innovación Y Salud, Universidad Complutense, Madrid, Spain, 2007
Visiting Scholar, University of Washington, Seattle, 2006–2007
Honorary Diploma for Outstanding Achievements, Polish Otolaryngological Society, 2005
Certificate of Appreciation for promoting equal opportunities for people with disabilities, Council for Disability Concerns, University of Michigan, 2003
Honorary Affiliate, Asociación Española de Audiología Experimental, 1996
Chercheur Ãtranger, Univ of Montpellier, France Laboratoire de Neurobiologie de l'Audition, Ins't Nat'l de la santé et de la recher médicale, 1994
Guest Professor, University of Tübingen, Germany, 1993
Citation for the Promotion of Hearing-Impaired Students in Prof Work Experiences, Nat'l Capital Assoc for Coop Education, Washington, DC, 1992
Distinguished Faculty Achievement Award, University of Michigan, 1989
Senator Jacob Javits Neuroscience Investigator Award, National Institutes of Health, NINCDS, 1984–1991
Fogarty Senior International Fellow, 1979–1980
Apralogs: Apramycin 5-O-Glycosides and Ethers with Improved Antibacterial Activity and Ribosomal Selectivity and Reduced Susceptibility to the Aminoacyltranserferase (3)-IV Resistance Determinant.
Quirke JCK, Rajasekaran P, Sarpe VA, Sonousi A, Osinnii I, Gysin M, Haldimann K, Fang QJ, Shcherbakov D, Hobbie SN, Sha SH, Schacht J, Vasella A, Böttger EC, Crich D.
J Am Chem Soc. 2020; 142: 530–44.
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.
For a list of publications from Michigan Research Experts, click HERE