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Auditory Development and Restoration Program

Michael Hoa, M.D., Otolaryngology Surgeon-Scientist

Research Statement

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 image

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 January 2020. L-R: Rafal T. Olszwski, Ph.D., Ian Taukulis, B.S., Shoujun Gu, Ph.D., Michael Hoa, M.D.

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. 

Lab Personnel

Selected Publications

Last Updated Date

October 28, 2020