Hirose Lab

fluorescence microscopy of macrophages in inner ear

Principal Investigator

Keiko Hirose, MD
Professor of Otolaryngology—Head & Neck Surgery

Overview

Dr. Hirose’s research program focuses on innate immunity of the inner ear and its influence on hearing. The main goal of her research program is to understand the effects of the immune response to inner ear injury.

For the past 20 years, she has studied cochlear inflammation and effects of leukocyte activation in the damaged mammalian cochlea. The observation that abundant leukocytes collected in the spiral ligament and spiral limbus after acoustic injury, in regions where there was rampant non sensory cell loss, suggested the possibility of bystander injury secondary to cochlear inflammation. This observation laid the groundwork for her first NIH grant.

In addition to studies on noise and ototoxicity, the Hirose lab now studies two important infectious causes of sensorineural hearing loss, pneumococcal meningitis and congenital CMV infection. Using mouse models, members of the Hirose lab study the effects of infectious processes on inner ear structure and function, on blood labyrinth barrier permeability and the contributions of the immune response to these changes.

Also, through a collaboration with University of Iowa, we are using mouse cochlear implantation to study the effects of materials, electrical stimulation and inner ear surgery on the inflammatory state of the inner ear and contributions to spiral ganglion cell survival and homeostasis of the cochlear environment.

Research Projects

Lab Team

  • Keiko Hirose, MD
  • Song-Zhe Li
  • Jacob Loredo
  • Dan Romano, MD

Collaborators:

  • Rutherford Lab
  • William Britt, UAB
  • Marlan Hansen, U Iowa

Funding

Richard G. Muench Chairman’s Grant from the American Hearing Research Foundation (2024)

NIH Active or Pending:

  • Inner Ear Infection and Innate Immunity. R01 DC021649 PI: Keiko Hirose
  • Inflammation and Hearing Loss Following Congenital CMV Infection. R01 DC015980 Co-Investigator. PI: William Britt, University of Alabama.
  • Role of Macrophages on Tissue Remodeling Following Cochlear Implantation.R01DC018488. Co-Investigator. PI: Marlan Hansen, University of Iowa
  • Macrophage Response to Otic Pathology R01 DC006283 Co-Investigator. PI: Mark Warchol

NIH Completed:

  • Mononuclear Phagocyte Activity in Cochlea Acoustic Trauma. K08 DC005761. PI: Keiko Hirose 
  • Cochlear Macrophages and Epithelial Repair. R01 DC011315 PI: Keiko Hirose 

Select Publications

View all of Dr. Hirose’s publications and collaborations »

  1. Slattery E, White AJ, Gauthier M, Linscott L, Hirose K*. Tolosa-Hunt syndrome masquerading as Gradenigo syndrome in a teenager. Int J Pediatr Otorhinolaryngol 2013;77(7):1219-21. doi: 10.1016/j.ijporl.2013.04.023. PMID: 23684166.
  2. Hirose K*, Li SZ, Ohlemiller KK, Ransohoff RM. Systemic lipopolysaccharide induces cochlear inflammation and exacerbates the synergistic ototoxicity of kanamycin and furosemide. J Assoc Res Otolaryngol 2014;15(4):555-70. doi: 10.1007/s10162-014-0458-8. PMCID: PMC4141430.
  3. Hirose K*, Hartsock JJ, Johnson S, Santi P, Salt AN. Systemic lipopolysaccharide compromises the blood-labyrinth barrier and increases entry of serum fluorescein into the perilymph. J Assoc Res Otolaryngol 2014;15(5):707-19. doi: 10.1007/s10162-014-0476-6. PMCID: PMC4164684.
  4. Kaur T, Hirose K, Rubel EW, Warchol ME. Macrophage recruitment and epithelial repair following hair cell injury in the mouse utricle. Front Cell Neurosci 2015;9:150. doi: 10.3389/fncel.2015.00150. eCollection 2015. PMCID: PMC4406144.
  5. Kaur T, Zamani D, Tong L, Rubel EW, Ohlemiller KK, Hirose K, Warchol ME. Fractalkine signaling regulates macrophage recruitment into the cochlea and promotes the survival of spiral ganglion neurons after selective hair cell lesion. J Neurosci 2015;35(45):15050-61. doi: 10.1523/JNEUROSCI.2325-15.2015. PMCID: PMC4642237.
  6. Wineland A, Menezes MD, Shimony JS, Shinawi MS, Hullar TE, Hirose K*.  Prevalence of Semicircular Canal Hypoplasia in Patients With CHARGE Syndrome: 3C Syndrome. JAMA Otolaryngol Head Neck Surg. 2016 Nov 10. doi: 10.1001/jamaoto.2016.3175. PMID: 27832265.
  7. Shinawi M and Hirose K*. Response to letter to the Editor: Prevalence of Semicircular Canal Hypoplasia in Patients with CHARGE Syndrome: 3C Syndrome. JAMA Otolaryngol Head Neck Surg. 2017 Feb 23.doi: 10.1001/jamaoto.2016.4765. PMID: 28241177.
  8. Vila PM, Ghogomu NT, Odom-John AR, Hullar TE, Hirose K*. Infectious complications of pediatric cochlear implants are highly influenced by otitis media. Int J Pediatr Otorhinolaryngol. Published online March 12, 2017. doi:10.1016/j.ijporl.2017.02.026. PMID: 28483256.
  9. Lichtenhan J, Hirose K, Buchman C, Duncan RK, Salt AN. Direct administration of 2-Hydroxypropyl-Beta-Cyclodextrin into guinea pig cochleae: Effects on physiological and histological measurements. PLoS One. 2017 Apr 6. doi: 10.1371/journal.pone.0175236. PMID: 28384320.
  10. Hirose K*, Rutherford M, Warchol M. Two cell populations participate in clearance of injured hair cells from the sensory epithelia of the inner ear. 2017 May 16. doi: 10.1016/j.heares.2017.04.006. PMID: 28526177.
  11. Gross JH, Bertrand M, Hirose, K*. Benign Rolandic epilepsy presenting like paradoxical vocal fold motion. Int J Pediatr Otorhinolaryngol. 2017 Sept 22. doi: 10.1016/j.ijporl.2017.09.021. PMID: 29106865
  12. Salt A, Hirose, K. Communication pathways to and from the inner ear and their contributions to drug delivery. Hear Res. 2018 May;362:25-37. doi: 10.1016/j.heares.2017.12.010. Epub 2017 Dec 19. PMID:
  13. Hirose K*, Li, Song-Zhe. The role of monocytes and macrophages in the dynamic permeability of the blood-perilymph barrier. Hear Res 2019 Mar 15;374: 49-57. doi: 10.1016/j.heares.2019.01.006. PMID: 30710792.
  14. Kim K, Payne S, Yang-Hood A, Li S, Davis B, Carlquist J, V-Ghaffari B, Gantz J, Kallogjeri D, Fitzpatrick J, Ohlemiller K, Hirose, K, Rutherford M. Vesicular Glutamatergic Transmission in Noise-induced Loss and Repair of Cochlear Ribbon Synapses. J Neurosci. 5 June 2019, 39 (23) 4434-4447; DOI: https://doi.org/10.1523/JNEUROSCI.2228-18.2019. PMID: 30926748
  15. Won Sung, CY, Seleme, M, Payne, S, Jonjic, S, Hirose, K, Britt, W. Virus-induced cochlear inflammation in newborn mice alters auditory function. JCI Insight. 5 September 2019; 4(17):e128878.DOI:https://doi.org/10.1172/ jci.insight.128878. PMID: 31484824; PMCID: PMC6777914.
  16. Brennan S, Molter D, Menezes M, Dunsky K, Leonard D, Lieu J, Hirose K, Hazan G, Horani A, Ferkol T, Brody L.  Implementation of a Screening Tool for Primary Ciliary Dyskinesia (PCD) in a Pediatric Otolaryngology Clinic.  Int J Pediatr Otorhinolaryngol. 2021 Mar; 142:110586. doi:10.1016/j.ijporl.2020.110586. Epub 2020 Dec 31. PMID: 33388601; PMCID:  PMC8021076.
  17. Claussen A, Quevedo R, Higgins T, Mostaert B, Rahman M, Hirose K, Hansen M.  Chronic Cochlear Implantation with and without Electric Stimulation in a Mouse Model Induces Robust Cochlear Influx of CX3CR1 Macrophages.  In BioRXIV. Hear Res. Dec 2022; 426:108510. PMID: 35527124.
  18. Rahman MT, Mostaert BJ, Hunger B, Saha U, Claussen AD, Razu I, Farjana N, Khan NA, Coleman S, Oleson J, Kirk J, Keiko H, Hansen MR. Contribution of macrophages to intracochlear tissue remodeling responses following cochlear implantation and neural survival. Res Sq [Preprint]. 2023 Jun 26:rs.3.rs-3065630. doi: 10.21203/rs.3.rs-3065630/v1. PMID: 37461619; PMCID: PMC10350110.
  19. Rahman MT, Hansen MR, Claussen AD, Mostaert B, Hunger B, Olesen J, Hirose K, Eckard P. Contribution of Macrophages to Neural Survival and Intracochlear Tissue Remodeling Responses Following Cochlear Implantation. J Neuroinflammation. 2023 Nov 10.

Contact Us

Mailing Address

660 S. Euclid Ave.
Campus Box 8115
St. Louis, MO  63110

Physical Address

4560 Clayton Ave.
Room 2118 (lab), 2262 (office)
St. Louis, MO  63110