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Auditory Development and Restoration Program
Michael Hoa, M.D., Otolaryngology Surgeon-Scientist
The Auditory Development and Restoration Program, which is part of the NIDCD Otolaryngology Surgeon-Scientist Program (OSSP), investigates the development and function of adult cochlear cell types and the pathophysiological processes that result in their structural and functional degeneration. The long-term goal of the laboratory is to establish a basis for ameliorating hearing fluctuation and to enable hearing restoration in the adult inner ear.
The endocochlear potential (EP) is essential for proper hair cell function and hearing. The structure and function of the lateral wall of the cochlea is central to the generation of this endocochlear potential. With this in mind, the lab seeks to: 1) use our understanding of stria vascularis development, structure, and function to identify mechanisms that connect dysfunctional inner ear ion homeostasis to hearing loss and hearing fluctuation; and 2) identify therapeutic strategies to treat strial-based hearing loss and hearing fluctuation.
Pathophysiology of the lateral wall has been implicated in age-related hearing loss (presbycusis), sudden sensorineural hearing loss, Ménière's disease, autoimmune inner ear disease, DFN3, and a diverse spectrum of inherited disorders, including Jervell and Lange-Nielson syndrome, Bartter syndrome, SeSAME syndrome, and Waardenburg syndrome. Ultimately, the lab’s research seeks to improve our understanding of the development and function of the stria vascularis. Investigations may provide insight into hearing loss related to pathology in the cochlear lateral wall, as well as potential avenues for therapeutic targeting of this pathology.
In the lab, we use mouse models to study stria vascularis function in the cochlear lateral wall. The stria vascularis is composed of three cell layers consisting of marginal cells on the luminal surface, intermediate cells in the central layer, and basal cells in the basolateral layer. The intermediate cell is fundamental to the generation of the EP, but it is the close interaction between the three cell types that results in a fully functional organ.
Stria vascularis cellular heterogeneity and organization
(A): Schematic of the stria vascularis (SV) and its relationship to structures in the cochlea. The SV is composed of three layers of cells and is responsible for generating the +80 mV endocochlear potential (EP) and the high potassium concentration in the endolymph-containing scala media. The relationship between the marginal, intermediate, and basal cells are demonstrated with the marginal extending basolateral projections to interdigitate with intermediate cells, which have bidirectional cellular projections that interdigitate with both marginal and basal cells. In addition to these cell types, other cell types, including spindle cells (yellow), endothelial cells, pericytes, and macrophages (not shown) are present in the SV.
(B): Cross-section of the stria vascularis in a postnatal, day 30 (P30) mouse immunostained with anti-SLC12A2 (marginal cells, red), anti-KCNJ10 (intermediate cells, green), and DAPI (4′,6-diamidino-2-phenylindole) for nuclei. Notice the interdigitation of cellular processes from both intermediate and marginal cells. Scale bar is 20 μm.
Source: Korrapati S, Taukulis I, Olszewski R, Pyle M, Gu S, Singh R, Griffiths C, Martin D, Boger E, Morell J, Hoa M. Single cell and single cell nucleus RNA-Seq reveal cellular heterogeneity and homeostatic regulatory networks in adult mouse stria vascularis. Front Mol Neurosci 2019 Dec 20.
doi: 10.3389/fnmol.2019.00316. eCollection 2019.
To investigate these interactions, the lab uses a combination of single-cell mRNA-sequencing, bioinformatics, fluorescent-activated cell sorting (FACS), adult and perinatal immunohistochemistry, confocal microscopy, animal auditory function testing, pharmacology, and molecular biology techniques.
Clinically, our program is interested in addressing the basis for hearing fluctuation disorders (i.e., Ménière's disease, sudden hearing loss, and autoimmune inner ear disease) and identifying potential novel therapies for these disorders.
Lab staff as of October 2020 (L-R): Rafal T. Olszwski, Ph.D., Ian Taukulis, B.S., Shoujun Gu, Ph.D., Michael Hoa, M.D.
- Gu S, Olszewski R, Nelson L, Gallego-Martinez A, Lopez-Escamez JA, Hoa M. Identification of potential Meniere's disease targets in the adult stria vascularis. Front Neurol. 2021 Feb 5;12:630561. doi: 10.3389/fneur.2021.630561. PMID: 33613436; PMCID: PMC7894210.
- Gu S, Olszewski R, Taukulis I, Wei Z, Martin D, Morell RJ, Hoa M. Characterization of rare spindle and root cell transcriptional profiles in the stria vascularis of the adult mouse cochlea. Sci Rep. 2020 Oct 22;10(1):18100. doi: 10.1038/s41598-020-75238-8. PMID: 33093630.
- Tona R, Lopez IA, Fenollar-Ferrer C, Faridi R, Anselmi C, Khan AA, Shahzad M, Morell RJ, Gu S, Hoa M, Dong L, Ishiyama A, Belyantseva IA, Riazuddin S, Friedman TB. Mouse models of human pathogenic variants of TBC1D24 associated with non-syndromic deafness DFNB86 and DFNA65 and syndromes involving deafness. Genes (Basel). 2020 Sep 24;11(10):E1122. doi: 10.3390/genes11101122. PMID: 32987832.
- Pyle MP, Hoa M. Applications of single-cell sequencing for the field of otolaryngology: A contemporary review. Laryngoscope Investig Otolaryngol. 2020 Apr 27;5(3):404-431. doi: 10.1002/lio2.388. PMID: 32596483; PMCID: PMC7314468.
- Hoa M, Olszewski R, Li X, Taukulis I, Gu S, DeTorres A, Lopez IA, Linthicum FH Jr, Ishiyama A, Martin D, Morell RJ, Kelley MW. Characterizing adult cochlear supporting cell transcriptional diversity using single-cell RNA-Seq: Validation in the adult mouse and translational implications for the adult human cochlea. Front Mol Neurosci. 2020 Feb 5;13:13. doi: 10.3389/fnmol.2020.00013. eCollection 2020.
- Morell RJ, Olszewski R, Tona R, Leitess S, Wafa TT, Taukulis I, Schultz JM, Thomason EJ, Richards K, Whitley BN, Hill C, Saunders T, Starost MF, Fitzgerald T, Wilson E, Ohyama T, Friedman TB, Hoa M. Noncoding microdeletion in mouse Hgf disrupts neural crest migration into the stria vascularis, reduces the endocochlear potential and suggests the neuropathology for human nonsyndromic deafness DFNB39. J Neurosci. 2020 Feb 4. pii: JN-RM-2278-19. doi: 10.1523/JNEUROSCI.2278-19.2020. [Epub ahead of print]
- Korrapati S, Taukulis I, Olszewski R, Pyle M, Gu S, Singh R, Griffiths C, Martin D, Boger E, Morell J, Hoa M. Single cell and single nucleus RNA-Seq reveal cellular heterogeneity and homeostatic regulatory networks in adult mouse stria vascularis. Front Mol Neurosci 2019 Dec 20. doi:10.3389/fnmol.2019.00316. eCollection 2019.
- Crossley J, Hussaini AS, Kim HJ, Hoa M. Meniere’s disease clinical subtypes in a population from the USA. J Laryngol Otol 2019 Dec 20:1-5. doi: 10.1017/S002221511900255X.
- Hancock M, Hoa M, Malekzadeh S. Educational resources for global health in otolaryngology. Otolaryngol Clin North Am 2018 Jun;51(3):563-574. doi: 10.1016/j.otc.2018.01.005. Epub 2018 Mar 7.
- DeTorres A, Olszewski R, Lopez I, Ishiyama A, Linthicum F, Hoa M. Supporting cell survival after cochlear implant surgery. Laryngoscope. 2019 Jan; 129(1): E36-E40. doi: 10.1002/lary.27539. Epub 2018 Oct 16.
- Sharlin DS, Ng L, Verrey F, Visser TJ, Liu Y, Olszewski RT, Hoa M, Heuer H, Forrest D. Deafness and loss of cochlear hair cells in the absence of thyroid hormone transporters Slc16a2 (Mct8) and Slc16a10 (Mct10). Sci Rep 2018; 8(1):4403.
- Imtiaz A, Belyantseva IA, Beirl AJ, Fenollar-Ferrer C, Bashir R, Bukhari I, Bouzid A, Shaukat U, Azaiez H, Booth KT, Kahrizi K, Najmabadi H, Maqsood A, Wilson EA, Waryah AM, Hoa M, Dong L, Morell RJ, Smith RJH, Riazuddin S, Masmoudi S, Kindt K, Naz S, Friedman TB. CDC14A phosphatase is essential for hearing and male fertility in mouse and human. Hum Mol Genet 2018; 27(5):780-798.
- Honda K, Kim SH, Kelly MC, Burns JC, Constance L, Li X, Zhou F, Hoa M, Kelley MW, Wangemann P, Morell RJ, Griffith AJ. Molecular architecture underlying fluid absorption by the developing inner ear. Elife 2017; 6(pii):e26851. doi: 10.7554/eLife.26851.
- Nakanishi N, Kawashima Y, Kurima K, Chae JJ, Ross AM, Pinto-Patarroyo G, Patel SK, Muskett JA, Ratay JS, Chattaraj P, Park YH, Grevich S, Brewer CC, Hoa M, Kim HJ, Butman JA, Broderick L, Hoffman HM, Aksentijevich I, Kastner DL, Goldbach-Mansky R, Griffith AJ. NLRP3 mutation and cochlear autoinflammation cause syndromic and nonsyndromic hearing loss DFNA34 responsive to anakinra therapy. Proc Natl Acad Sci USA 2017;114(37):E7766-E7775.
- Hoa M, Friedman RA, Fisher LM, Derebery MJ. Prognostic implications of and audiometric evidence for hearing fluctuation in Meniere’s disease. Laryngoscope 2015 Sep 7. doi: 10.1002/lary.25579.[Epub ahead of print]
- Burns JC, Kelly MC, Hoa M, Morell RJ, Kelley MW. Single-cell RNA-Seq resolves cellular complexity in sensory organs from the neonatal inner ear. Nat Commun 2015;6:8557.
- Dhillon VK, Hoa M, Winter M, Wilkinson EP. Extrusion of a cochlear implant positioner through the tympanic membrane in a pediatric patient: Management of a delayed complication. Ann Otol Rhinol Laryngol 2014;123(8):537-540.
- Hoa M, Wilkinson EP, Slattery WH 3rd. Delayed recovery of speech discrimination after fractionated stereotactic radiotherapy for vestibular schwannoma in neurofibromatosis 2. Ear Nose Throat J 2014;93(2):E20-2.
- Hoa M, Linthicum FH Jr. Spiral ganglion deficiency in adult-onset deafness-dystonia syndrome. Otol Neurotol 2013;34(9):e130-1. doi: 10.1097/MAO.0b013e3182a09b3b
- Hoa M, House JW, Linthicum FH Jr., Go JL. Petrous apex cholesterol granuloma: Pictorial review of radiologic considerations in diagnosis and surgical histopathology. J Laryngol Otol 2013; 127(4):339-48.
- Friedman RA, Hoa M, Brackmann DE. Surgical management of endolymphatic sac tumors. J Neurol Surg B 2013; 74(01):012-019. doi: 10.1055/s-0032-1329622
- Hoa M, Drazin D, Hanna G, Schwartz M, Lekovic GP. The approach to the patient with incidentally diagnosed vestibular schwannoma. Neurosurg Focus 2012; 33(3):E2.
- Hoa M, House JW, Linthicum FH Jr. Petrous apex cholesterol granuloma: Maintenance of the drainage pathway, the histopathology of surgical management, and histopathologic evidence for the exposed marrow theory. Otol Neurotol 2012; 33(6):1059-65.
- Hoa M, Slattery WH 3rd. Update on neurofibromatosis 2. Otolaryngol Clin N Am 2012; 45(2):315-32, viii.
- Wilkinson EP, Hoa M, Slattery WH 3rd, Fayad JN, Friedman RA, Brackmann DE. Evolution in the management of facial nerve schwannoma. Laryngoscope 2011; 121(10):2065-74.
- Slattery WH, Hoa M, Bonne N, Friedman RA, Schwartz MS, Fisher L, Brackman DE. Middle fossa decompression for hearing preservation: A review of institutional results and indications. Otol Neurotol 2011; 32(6):1017-24.
- Hoa M, Syamal M, Schaeffer MA, Sachdeva L, Berk R, Coticchia J. Biofilms and chronic otitis media: An initial exploration into the role of biofilms in the pathogenesis of chronic otitis media. Am J Otolaryngol 2010; 31(4):241-5.