Department

• Biomedical Sciences

Position

• Professor

Secondary Appointment

• Pathology

My unique expertise in mechanisms of iatrogenic hearing loss originates from acquiring hearing loss via treatment with the life-saving aminoglycosides when afflicted with bacterial meningitis as an infant. I recognize how critical it is to translate our now wide-ranging collective knowledge in the etiologies of hearing loss and vestibular disorders into efficacious strategies that preserve or restore optimal hearing and vestibular function to maximize the personal goals, familial relationships, friendships and career trajectories of those afflicted with these sensory disorders.  
 

Books

• Steyger PS. Inflammation Potentiates Cochlear Uptake of Ototoxins and Drug-Induced Hearing Loss . In: Inflammatory Mechanisms in Mediating Hearing Loss. Ramkumar V, Rybak LP, editors. Cham: Springer; 2018. Chapter 7; p.133-147. 237p.
   , Springer Publishing, 2018

Articles

• Kros CJ, Steyger PS. Aminoglycoside- and Cisplatin-Induced Ototoxicity: Mechanisms and Otoprotective Strategies. Cold Spring Harb Perspect Med. 2019 Nov 1;9(11). Review. PubMed PMID: 30559254; PubMed Central PMCID: PMC6579718. http://perspectivesinmedicine.cshlp.org/content/9/11/a033548.abstract. , Perspectives in Medicine, 9(11), 2019
• Jiang M, Li H, Johnson A, Karasawa T, Zhang Y, Meier WB, Taghizadeh F, Kachelmeier A, Steyger PS. Inflammation up-regulates cochlear expression of TRPV1 to potentiate drug-induced hearing loss. Sci Adv. 2019 Jul;5(7):eaaw1836. doi:10.1126/sciadv.aaw1836. eCollection 2019 Jul. PubMed PMID: 31328162; PubMed Central PMCID: PMC6636990. https://advances.sciencemag.org/content/5/7/eaaw1836.abstract.
   , Science Advances, Jul;5(7), 2019
• Nyberg S, Abbott NJ, Shi X, Steyger PS, Dabdoub A. Delivery of therapeutics to the inner ear: The challenge of the blood-labyrinth barrier. Sci Transl Med. 2019 Mar 6;11(482). doi:10.1126/scitranslmed.aao0935. Review. PubMed PMID: 30842313; PubMed Central PMCID: PMC6488020. https://stm.sciencemag.org/content/11/482/eaao0935/tab-article-info., Science Translational Medicine, 11, 482, 2019
• Adler HJ, Ratnanather JT, Steyger PS, Buran BN. Scientists with Hearing Loss Changing Perspectives in STEMM. Acoust Today. 2019 Spring;15(1):66-70. PubMed PMID: 31423114; PubMed Central PMCID: PMC6697183. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6697183/
   , Acoustics Today, 15(1), 66-70, 2019
• Kachelmeier A, Shola T, Meier WB, Johnson A, Jiang M, Steyger PS. Simplified, automated methods for assessing pixel intensities of fluorescently-tagged drugs in cells. PLoS One. 2018;13(11):e0206628. doi: 10.1371/journal.pone.0206628. eCollection 2018. PubMed PMID: 30383813; PubMed Central PMCID: PMC6211712. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6211712/
   , PLoS One, 13(11), 2018
• Garinis AC, Kemph A, Tharpe AM, Weitkamp JH, McEvoy C, Steyger PS. Monitoring neonates for ototoxicity. Int J Audiol. 2018 Sep;57(sup4):S41-S48. doi: 10.1080/14992027.2017.1339130. Epub 2017 Jun 22. Review. PubMed PMID: 28949262; PubMed Central PMCID: PMC5741535. https://www.ncbi.nlm.nih.gov/pubmed/28949262
   , 57(sup4), S41-S48, 2018

Editing and Reviews

• Steyger PS, Cunningham L, Esquivel C, Watts K and Zuo J (2018). Editorial: Cellular Mechanisms of Ototoxicity. Front. Cell. Neurosci. 12:75. PMID: 29636663 PMCID: PMC5881100. https://doi.org/10.3389/fncel.2018.00075
   , Frontiers in Cellular Neuroscience, 2018

Presentations

• Poster Presentation:  F Taghizadeh, M Jiang, W Meier, P Steyger.  TLR4 and MyD88 Activation of TRPV1 Modulates Cellular Uptake of Aminoglycosides. 45th Annual Mid-Winter Meeting of the Association for Research in Otolaryngology, San Jose, CA, 1/2020, 2020
• Podium Presentation:  F Taghizadeh, M Jiang, W Meier, P Steyger TLR4 and MyD88 activation of TRPV1 modulates cellular uptake of aminoglycosides. 2nd International Society for Inner Ear Therapeutics, Hannover, Germany, 11/2019, 2019
• Keynote speaker:  Otopathology of ototoxicity and noise exposure:  From animal models to audiological management, NCRAR biennial conference, Portland VA, OR, Sept 2019, 2019

Research and Scholarship Interests

• Ototoxicity
  Cochleotoxicity
  Vestibulotoxicity
  Aminoglycoside-induced toxicity
  Cisplatin-induced toxicity
  Mechanisms of neuro- and cytotoxicity
  Physiology of Blood-Labyrinth Barrier
  Trafficking of drugs and nutrients across blood barriers
  Hearing Loss
  Inflammation

Current Research Projects

• I direct a research laboratory funded by NIH-NIDCD to identify the mechanisms by which circulating ototoxic drugs cross the blood-labyrinth barrier into the cochlear fluids and enter sensory hair cells to induce cytotoxicity that leads to permanent hearing loss.
  As a laboratory, we focus primarily on the trafficking mechanisms utilized by aminoglycoside antibiotics.  We recently identified that inflammation and inflammatory mediators enhance cochlear uptake of aminoglycosides and exacerbates aminoglycoside-induced hearing loss (a-c).  Much of the expertise gained in understanding the mechanisms of aminoglycoside hearing loss have led to analogous studies for the cochleototoxic anti-cancer drug, cisplatin, and further improve our understanding of the mechanisms of cisplatin-induced ototoxicity (d). 
  More recently, we have initiated human studies to determine if (i) clinical evidence of systemic inflammation increases the risk of hearing loss in sick neonates dosed with aminoglycosides, and (ii) whether subpopulations of subjects with cystic fibrosis have a greater genetic susceptibility (or resistance) to aminoglycoside-induced ototoxicity. 
  I am a primary author of multiple nonclinical and human articles that discuss the inflammatory and pharmacogenomic risk factors described above, and are currently under investigation,
  
  a.     Koo JW, Wang Q, Steyger PS (2011) Infection-mediated vasoactive peptides modulate cochlear uptake of fluorescent gentamicin.  Audiology & Neurotology, 16: 347-358.  PMID 21196726   PMCID:  PMC3023003
  b.     Koo JW, Quintanilla-Dieck L, Jiang M, Liu J, Urdang ZD, Allensworth JJ, Cross CC, Li H, Steyger PS (2015)  Endotoxemia-mediated inflammation potentiates aminoglycoside-induced ototoxicity. Science Translational Medicine 7(298): 298ra118. doi: 10.1126/scitranslmed.aac5546.  PMID:  26223301   PMCID:  PMC4534720
  c.      Jiang M, Li H, Johnson A, Karasawa T, Zhang Y. Meier WB, Taghizadeh F, Kachelmeier A, Steyger PS  (2019)  Inflammation upregulates cochlear expression of TRPV1 to potentiate drug-induced hearing loss  Science Advances 5(7) eaaw1836.  PMID:  31328162   PMCID:  PMC6636990
  d.     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
   

Grant Funding Received

• NIH/NIDCD: Cochlear trafficking and hair cell uptake of aminoglycosides Specific aim: to identify the effect of systemic inflammation on aminoglycoside uptake and subsequent ototoxicity in the cochlea in vivo.
• NTSBRDF/State of Nebraska: The Mechanism, and Clinical Risk, of Drug-Induced Hearing Loss The specific aims are the setup up a new research laboratory with the following specific aims: (i) Identify the molecular mechanisms for AGs to cross the strial BLB and enter hair cells; (ii) Define the signaling pathways by which inflammation potentiates AG-induced ototoxicity; and (iii) What is the clinical risk of drug-induced hearing loss in neonates?
• NIH/NIDCD: Clinical factors in aminoglycoside-induced ototoxicity Specific aims are to determine (i) if gentamicin dose-dependently increases hearing loss in infants, and (ii) verify if (suspected) sepsis potentiates gentamicin-induced hearing loss in infants. If gentamicin-induced hearing loss in NICU graduates is (i) dose-dependent, and/or (ii) potentiated by (suspected) sepsis, these data will predicate the need for ototoxicity monitoring prior to, and following, discharge from the NICU.
• Cystic Fibrosis Foundation: Genetic Markers for Susceptibility or Resistance to Ototoxicity
• Office of Naval Research/University of Montana Subaward (Zuo/Steyger, subcontract PIs) “Trans-Middle Ear Drug Delivery”. Specific aims are to develop an in vitro screening tool to identify therapeutics for non-invasive local delivery to the inner ear via eardrops.

• University Research Award, Creighton University, 2021
• Keynote Speaker, NCRAR biennial conference, 2019
• Guest Editor, Frontiers in Celluar Neuroscience, 2018
• Guest Editor, Frontiers in Celluar Neuroscience, 2018
• Lead Discussant, Hearing Center of Excellence (DOD), 2016
• Associate Editor, Frontiers in Medicine - Translational Medicine, 2016