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Lead Researcher

Hainan Lang, M.D., Ph.D.

mail langh@musc.edu call 18437928483

Professor
Department of Pathology & Laboratory Medicine
Office: Room 401 Walton Research Building
Email: langh@musc.edu
Phone: 843-792-8483

Research Interests

Genetically modified mouse models and human inner ear tissues have been used for understanding the cellular and molecular mechanisms of auditory nerve survival and degeneration in several pathological conditions, including aging, exposure to noise and ototoxic drugs and genetic defects. We focus on the functional roles of glial cell dysfunction, neural crest cell associated transcription factors, RNA binding proteins, complement system, and their related regulatory networks for enhancing remyelination, preventing or protecting the auditory nerve from degeneration and promoting auditory nerve survival and functional recovery after cochlear injury. This translational research program provides an outstanding training opportunity for (1) cutting-edge cellular and molecular procedures in hearing research such as molecular imaging of living cochlear cells, 3D cell culture assay, and RNA-seq analysis of the degenerative cochlea; (2) processing and examination of mouse and human temporal bone tissues; (3) contemporary histopathological and high-resolution imaging techniques to assay human and animal inner ear specimens; and 4) evaluation of auditory function using electrophysiological techniques including the measurements of auditory nerve compound action potentials, spontaneous activities of single auditory nerve fiber, and auditory brainstem responses. The research program has been supported by grants from NIH/NIDCD for more than 20 years.

This is an exciting and newly developed project, which addresses the novel hypothesis that abnormal macrophage-related activities, resulting from gene deficiency, lead to hearing loss and that these changes may be associated with communication impairment in Autism Spectrum Disorder (ASD) and other neurodevelopmental disorders. For example, mutations or deletions in the MEF2C gene have recently been linked to ASD. In collaboration with Dr. Christopher Cowan from the Department of Neuroscience our experiments revealed that Mef2c is highly expressed in cochlear macrophages in postnatal mice and that Mef2c hypofunction results in auditory nerve functional decline and hearing loss. This research is now supported by a research grant from the Simmons Foundation (SFARI Pilot Award) and an R01 grant from NIH/NIDCD.

Our research on isolation of adult neural stem/progenitor cells from the adult mouse auditory nerve is aimed at replacing damaged spiral ganglion neurons, preventing neuron degeneration and promoting auditory functional recovery. Several lines of studies are ongoing with a focus on remyelination and de-differentiation of adult glial cells after acute auditory nerve injury resulting from noise- or ototoxic drug-exposure. A variety of advanced methods are employed to 1) isolate and expand neural stem/progenitor cells; 2) purify and characterize neural stem/progenitor cells using transgenic mouse models and fluorescence-activated cell sorting; and 3) identify the molecular characteristics of neural stem/progenitor cells using next generation sequencing, gene expression profiling at the single cell level (e.g., single cell RNA-seq), complementary proteomics assays and super resolution imaging analysis.

Selected Recent Publications

  1. Cho JY, Rumschlag JA, Tsvetkov E, Proper DS, Lang H, Berto S, Assali A, Cowan CW (2024). MEF2C hypofunction in GABAergic cells alters sociability and prefrontal cortex inhibitory synaptic transmission in a sex-dependent manner. Biol Psychiatry Glob Open Sci. 4(2):100289. PMCID: PMC1088131.
  2. Lang H, Noble KV, Barth JL, Rumschlag JA, Jenkins TR, Storm SL, Eckert MA, Dubno JR, Schulte BA (2023). The stria vascularis in mice and humans is an early site of age-related cochlear degeneration, macrophage dysfunction, and inflammation. J Neurosci 43, 5057-5075. PMCID: PMC10324995.
  3. Brown LN, Barth JL, Jafri S, Rumschlag JA, Jenkins TR, Atkinson C, Lang H (2023). Complement factor B is essential for the proper function of the peripheral auditory system. Front Neurol 14:1214408. PMCID: PMC10408708.
  4. McChesney N, Barth JL, Rumschlag JR, Tan J, Harrington AJ, Noble KV, McClaskey CM, Elvis P, Vaena SG, Romeo MJ, Harris KC, Cowan CW, Lang H (2022). Peripheral auditory nerve impairment in a mouse model of syndromic autism. J Neurosci 42, 8002-8018 (Selected for cover photo). PMCID: PMC9617620.
  5. Rumschlag JA, McClaskey CM, Dias JW, Kerouac LB, Noble KV, Panganiban C, Lang H, Harris KC (2022). Age-related central gain with degraded neural synchrony in the auditory brainstem of mice and humans. Neurobiol Aging 115, 50-59. PMCID: PMC9153923.
  6. Panganiban CH, Barth JL, Tan J, Noble KV, McClaskey CM, Howard BA, Jafri SH, Dias JW, Harris KC, Lang H (2021). Two distinct types of nodes of Ranvier support auditory nerve function in the mouse cochlea. Glia 70, 768-791. PMCID: PMC8994501.
  7. Liu T, Li G, Noble KV, Li Yong, Barth JL, Schulte BA, Lang H (2019). Age-dependent alterations of Kir4.1 expression in neural crest-derived cells of the mouse and human cochlea. Neurobiol Aging 18, 80:210-222. PMCID: PMC6679794.
  8. Noble KV, Liu T, Matthews L, Schulte BA, Lang H (2019). Age-related alterations in resident immune cells of the human cochlea. Front Neurol 10, 895. PMCID: PMC6707808.
  9. Noble KV, Reyzer ML, Barth JL, McDonald H, Tuck M, Schey KL, Krug EL, Lang H (2018). Use of proteomic imaging coupled with transcriptomic analysis to identify biomolecules responsive to cochlear injury. Front Mol Neurosci 11,243. PMCID: PMC30065626.
  10. Panganiban CH, Barth JL, Darbelli L, Xing Y, Zhang J, Li H, Noble KV, Liu T, Brown LN, Schulte BA, Richard S, Lang H (2018). Noise-induced dysregulation of Quaking RNA binding proteins contributes to auditory nerve demyelination and hearing loss. J Neurosci 38, 2551-2568. PMCID: PMC5858596.
  11. Brown LN, Xing Y, Noble KV, Barth JL, Panganiban CH, Smythe NM, Bridges MC, Zhu J, Lang H (2017). Macrophage-mediated glial cell elimination in the postnatal mouse cochlea. Front Mol Neurosci10, 407. PMCID: PMC5770652.
  12. Lang H, Nishimoto E, Xing Y, Brown LN, Noble KV, Barth JL, LaRue AC, Ando K, Schulte BA (2016). Contributions of mouse and human hematopoietic cells to remodeling of the adult auditory nerve after neuron loss. Mol Ther 24, 2000-2011. PMCID: PMC5154482.
  13. Lang H, Xing Y, Brown LN, Samuvel DJ, Panganiban CH, Havens LT, Balasubramanian S, Wegner M, Krug EL, Barth JL (2015). Neural stem/progenitor cell properties of glial cells in the adult mouse auditory nerve. Sci Rep 5, 3383. PMCID: PMC4549618.

A List of Published Work in My Bibliography

Laboratory Members

Tyreek Jenkins, Ph.D. candidate

171 Ashley Avenue, WRB RS304
Charleston, SC 29425

Shelby Ashton Payne, M.D. /, Ph.D. candidate

171 Ashley Avenue, WRB RS304
Charleston, SC 29425

Emily Fabrizio-Stover, Ph.D.

171 Ashley Avenue, WRB RS610
Charleston, SC 29425

Olivia Lopez, B.S. MUSC PREP Scholar

171 Ashley Avenue, WRB RS304
Charleston, SC 29425

Jiaying Wu, B.S., M.S. Research Specialist

171 Ashley Avenue, WRB RS304
Charleston, SC 29425

Juhong Zhu, B.S., M.S.

Research Specialist

171 Ashley Avenue, WRB RS304
Charleston, SC 29425