Graduate Studies Faculty
Peter Steyger, Ph.D.
Programs: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 RotationsDr. Steyger has not indicated availability for preceptor rotations at this time.
Faculty MentorshipDr. 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
- 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
- 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
- Dai CF, Steyger PS (2008) A systemic gentamicin pathway across the stria vascularis. Hearing Research 235, 114-124. PMID: 18082985 PMCID: PMC2703593
- 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
- Steyger PS, Karasawa, T (2008) Intra-cochlear trafficking of aminoglycosides. Communicative and Integrative Biology, 1, 140-142. PMID: 19704872 PMCID: PMC3662252
- 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
- Wang Q,Steyger PS (2009)Trafficking of systemic fluorescent gentamicin into the cochlea and hair cells. JARO 10, 205-219. PMID: 19255807 PMCID: PMC2674203
- 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
- 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
- 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
- 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
- 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
- Li H, Steyger PS (2011) Systemic aminoglycosides are trafficked via endolymph into hair cells. Scientific Reports 1, 159. PMID: 22355674 PMCID: PMC3240991
- 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
- 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