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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.

Research Publications

Nelson RF
, Glenn KA, Miller VM, Wen H, Paulson HL. A novel route for F-box protein-mediated ubiquitination links CHIP to glycoprotein quality control. J Biol Chem. 2006;281(29):20242-20251. PMID: 16682404

Nelson RF, Glenn KA, Zhang Y, Wen H, Knutson T, Gouvion CM, Robinson BK, Zhou Z, Yang B, Smith RJH, Paulson HL. Selective cochlear degeneration in mice lacking the F-box protein, Fbx2, a glycoprotein-specific ubiquitin ligase subunit. Journal of Neuroscience. 2007;27(19):5163-5171. PMID: 17494702

Elghouche AN, Nelson RF, Hashino E. (2017) Inner Ear Organoids: Recapitulating Inner Ear Development in 3D Culture. In: Tsuji T (eds.) Organ Regeneration Based on Developmental Biology. Springer, Singapore.

Tang PC, Alex AL, Nie J, Lee J, Roth AA, Booth KT, Koehler KR, Hashino E, Nelson RF, Defective Tmprss3-Associated Hair Cell Degeneration in Inner Ear Organoids, Stem Cell Reports, 2019 Jul 9;13(1):147-162. PMID: 31204303

Tang PC, Hashino E, Nelson RF. Progress in Modeling and Targeting Inner Ear Disorders with Pluripotent Stem Cells, Stem Cell Reports, June 9, Online May 21, 2020

Primary Investigator

23096-Nelson, Rick

Rick F. Nelson, MD, PhD

Associate Professor of Otolaryngology-Head & Neck Surgery

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