Graduate Studies Faculty

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Peter Steyger, Ph.D.

Professor of Otolaryngology - Head and Neck Surgery
Affiliate Investigator, NCRAR
Admin Unit: Oregon Hearing Research Center
Phone: 503-494-1062
Lab Phone: 503-494-2373
Fax: 503-494-5656
Office: NRC 413
Mail Code: NRC04
Neuroscience Graduate Program
Research Interests:
ototoxicity, auditory neuroscience, molecular responses to ototoxic drug uptake, drug-binding proteins, pharmacokinetics, drug permeation of cation channels, drug trafficking across endothelial and epithelial barriers, translational research, synergism of drug-induced ototoxicity by noise or inflammatory responses » Click here for more about Dr. Steyger's research » PubMed Listing
Preceptor Rotations
Dr. Steyger has not indicated availability for preceptor rotations at this time.
Faculty Mentorship
Dr. Steyger has not indicated availability as a mentor at this time.

Summary of Current Research

Aminoglycoside antibiotics are essential for battling life-threatening Gram-negative bacterial infections, e.g., meningitis, and in preventing infection in burns, blast injuries and premature babies. However, aminoglycosides also cause ototoxicity by killing the sensory cells in the inner ear that detect sound and motion, resulting in hearing loss, and vestibular deficits, leading to auditory and vestibular dysfunction, couplked with language, educational, and psycho-social delays in patients. Our overall aim is to identify, and then prevent the cellular mechanisms that initiate drug-induced hair cell death. The long-term goal of this project is to develop interventional strategies that will allow future clinicians to use aminoglycosides without serious side-effects.

Aminoglycosides predominantly enter cochlear hair cells across their apical membranes through non-selective cation channels, and by endocytosis from a unique extra-cellular fluid - endolymph. The laboratory investigates how aminoglycosides are transported across the cellular components of blood-labyrinth barrier into endolymph, from where they can then enter and kill sensory hair cells. This involves characterizing the mechanisms by which aminoglycosides enter (and leave) cells.



Other projects are focused on:

  1)  identifying novel gentamicin-binding proteins and lipids using mass spectroscopy,

  2)  how noise potentiates the ototoxicity of aminoglycosides, and

  3)  cisplatin trafficking in the cochlea.



The lab uses fluorescently-conjugated ototoxic drugs, fluorescent reporters of cell physiology, cell culture, confocal microscopy, molecular, biochemical and in vivo techniques to conduct their investigations, primarily funded by the National Institute of Deafness and Other Communications Disorders.



Selected Recent Publications

  1. Myrdal SE, Johnson, KE, Steyger PS (2005) Cytoplasmic and intra-nuclear binding of gentamicin does not require endocytosis. Hearing Research 204:156-169.  PMID: 15925201   PMCID: PMC2736065
  3. Dai CF, Mangiardi D, Cotanche DA, Steyger PS (2006) Uptake of fluorescent gentamicin by vertebrate hair cells in vivo. Hearing Research 213, 64-78.  PMID: 16466873   PMCID: PMC2736064
  5. Dai CF, Steyger PS (2008) A systemic gentamicin pathway across the stria vascularis. Hearing Research 235, 114-124.  PMID: 18082985   PMCID: PMC2703593
  7. Karasawa T, Wang Q, Fu Y, Cohen DM, Steyger PS (2008) TRPV4 enhances cellular uptake of aminoglycoside antibiotics. J Cell Science 121, 2871-2879.  PMID: 18682499   PMCID: PMC2736053
  9. Steyger PS, Karasawa, T (2008) Intra-cochlear trafficking of aminoglycosides. Communicative and Integrative Biology, 1, 140-142. PMID: 19704872   PMCID: PMC3662252
  11. Li H, Steyger PS(2009) Synergistic ototoxicity due to noise exposure and aminoglycoside antibiotics. Noise and Health 11, 26-32.  PubMed PMID: 19265251   PMCID: PMC2713742
  13. Wang Q,Steyger PS (2009)Trafficking of systemic fluorescent gentamicin into the cochlea and hair cells. JARO 10, 205-219.  PMID: 19255807   PMCID: PMC2674203
  15. Karasawa T, Wang Q, Fu Y, David LL, Steyger PS (2010) CLIMP-63 is a gentamicin-binding protein that is involved in drug-induced cytotoxicity. Cell Death and Disease 1, e102.  PMID:  21368867   PMCID: PMC3032319
  17. Li H, Wang Q, Steyger PS (2011) Acoustic trauma increases cochlear and hair cell uptake of gentamicin. PLoSOne 6(4): e19130.  PMID: 21552569   PMCID: PMC3084257
  19. Alharazneh A, Luk L, Huth M, Monfared A, Steyger PS, Cheng A, Ricci A (2011) Aminoglycosides rapidly and selectively enter inner ear hair cells via mechanotransducer channels. PLoS One 6(7): e22347.  PMID: 21818312   PMCID: PMC3144223
  21. Stepanyan R, Indzhykulian AA, Boger ET, Steyger PS, Friedman TB, Frolenkov GI(2011) TRPA1-mediated uptake of aminoglycosides in mouse cochlear outer hair cells. Journal of the Association for Research in Otolaryngology 12, 729-40.  PMID:  21879401   PMCID: PMC3214240
  23. KarasawaT, Wang Q, David L, Steyger PS (2011) Calreticulin binds to gentamicin and reduces drug-induced cytotoxicity  Toxicological Sciences 124, 378-87.  PMID:  21785162   PMCID: PMC3216409
  24. Li H, Steyger PS (2011) Systemic aminoglycosides are trafficked via endolymph into hair cells.  Scientific Reports 1, 159.  PMID: 22355674   PMCID: PMC3240991
  26. Brock P, Knight K, Freyer D, Campbell KCM, Steyger PS, Blakley BW, Rassekh SR, Chang K, Fligor B, Rajput K., Sullivan M, Neuwelt EA (2012) Platinum-induced ototoxicity in children: a consensus review on mechanisms, predisposition and protection including a new SIOP Boston Ototoxicity Scale.  Journal of Clinical Oncology 30(19) 2408-2417 PMID: 22547603   PMCID: PMC3675696
  28. Quintanilla-Dieck L, Larrain B, Trune D, Steyger PS (2013) Effect of systemic lipopolysaccharide-induced inflammation on cytokine levels in the murine cochlea: a pilot study. Otolaryngology - Head and Neck Surgery 149, 301-3.  PubMed PMID: 23736811   PMCID: in process