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Nelson Lab

The Nelson Lab, led by Rick Nelson, MD, PhD, is interested in elucidating the mechanisms that underlie hair cell degeneration as it relates to deafness and balance disorders.

Active Research

This laboratory team currently focuses on why serine proteases are critical for the survival of hair cells in the inner ear and what cellular pathways mediate hair cell degeneration and deafness. Currently, the goal of this research is to understand how type II transmembrane serine protease 3 (TMPRSS3) functions, to identify and define the mechanisms that lead to hair cell degeneration and to develop therapeutic strategies for deafness and balance disorders.

Loss of mechanosensitive hair cells in the inner ear is a leading cause of profound hearing loss and balance disorders, affecting millions of people. Human inner ear hair cell fail to regenerate once they are lost. To date, more than 110 genes have been implicated in causing autosomal recessive congenital deafness and most of these gene mutations lead to degeneration of inner ear hair cells. The Nelson Lab aims to increase knowledge on how hair cell degenerate due to genetic mutations. Elucidating the mechanisms of hair cell degeneration is crucial to the treatment of inner ear disorders.

Human mutations in TMPRSS3 leads to autosomal recessive deafness (DFNB8/10).  Mouse mutants of Tmprss3 (Tmprss3Y260X) show normal development of hair cells followed by rapid degeneration of hair cells over 48 hours. The mechanism of why TMPRSS3 is critical for hair cell survival is currently unknown.

In the Nelson Lab, we use a novel stem cell derived 3D inner ear organoids and mutant mice to study the mechanisms of genetically-mediated hair cell degeneration. The lab also uses CRISPR/Cas9 gene editing, single cell RNA-seq and proteomics to determine the cellular pathways impacted by deafness causing gene mutations.

Learn more about TMPRSS3

Research Publications

Early Wnt signaling activation promotes inner ear differentiation via cell caudalization in mouse stem cell-derived organoids. Tang PC, Chen L, Singh S, Groves AK, Koehler KR, Liu XZ, Nelson RF. Stem Cells. 2022 Sep 25:sxac071. doi: 10.1093/stmcls/sxac071. Online ahead of print.PMID: 36153788 

TMPRSS3 expression is limited in spiral ganglion neurons: implication for successful cochlear implantation. Chen YS, Cabrera E, Tucker BJ, Shin TJ, Moawad JV, Totten DJ, Booth KT, Nelson RF. J Med Genet. 2022 Aug 12:jmedgenet-2022-108654. doi: 10.1136/jmg-2022-108654. Online ahead of print.PMID: 35961784

Deafness-in-a-dish: modeling hereditary deafness with inner ear organoids. Romano DR, Hashino E, Nelson RF. Hum Genet. 2022 Apr;141(3-4):347-362. doi: 10.1007/s00439-021-02325-9. Epub 2021 Aug 3.PMID: 34342719 

Progress in Modeling and Targeting Inner Ear Disorders with Pluripotent Stem Cells. Tang PC, Hashino E, Nelson RF. Stem Cell Reports. 2020 Jun 9;14(6):996-1008. doi: 10.1016/j.stemcr.2020.04.008. Epub 2020 May 21.PMID: 32442531 
Defective Tmprss3-Associated Hair Cell Degeneration in Inner Ear Organoids. Tang PC, Alex AL, Nie J, Lee J, Roth AA, Booth KT, Koehler KR, Hashino E, Nelson RF. Stem Cell Reports. 2019 Jul 9;13(1):147-162. doi: 10.1016/j.stemcr.2019.05.014. Epub 2019 Jun 13.PMID: 31204303 
primary investigator
23096-Nelson, Rick

Rick F. Nelson, MD, PhD

Professor of Otolaryngology-Head & Neck Surgery

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