# Genetically Mediated Hair Cell Degeneration in 3D Inner Ear Organoids

> **NIH NIH K08** · INDIANA UNIVERSITY INDIANAPOLIS · 2021 · $178,830

## Abstract

PROJECT SUMMARY
This proposal describes a 5-year training program for the development of a clinician-scientist investigator in
stem cell biology and large-scale genomics. The primary goal of this application is to serve as a basis for
training Rick Nelson, MD, PhD in the critical skills necessary to become an independent scientific investigator
studying inner ear hair cell degeneration. Dr. Nelson is currently an Assistant Professor at Indiana University
School of Medicine where he will expand his scientific skills through course work, university resources and
mentoring. Hearing loss and vestibular dysfunction affect millions of people worldwide and the common
pathophysiologic finding is loss of the mechanosensitive hair cells. Eri Hashino, PhD will serve as Dr. Nelson's
primary mentor and train him in stem cell biology. Dr. Hashino is an international leader is stem cell biology
and has trained numerous postdoctoral fellows and clinician-scientists. Richard JH Smith, MD at University of
Iowa will serve as Dr. Nelson's co-mentor and train him in large-scale genomic approaches and bioinformatics.
Dr. Smith is an internationally renowned clinician-scientist and leader in human genetics. Dr. Nelson will also
enroll in the Independent Investigator Incubator (I3) program at Indiana University, which provides guidance in
scientific and career development. D. Wade Clapp, MD is an internationally recognized clinician-scientist who
will serve as a career advisor for Dr. Nelson. His advisory committee will provide broad expertise that spans
research planning and career development. In this proposal, the PI will establish a novel model of hair cell
degeneration using mouse stem cell-derived 3D cultures containing mechanosensitive hair cells. CRISPR
gene editing technology will be used to disrupt the Tmprss3 gene, which is known to cause hair cell
degeneration in mice and humans. Next, the PI will use proteomic approaches to establish the protein
interactome of the Tmprss3 serine protease in hair cells. Finally, single-cell RNA sequencing (RNA-seq)
technology will be used to study global alterations in gene expression that lead to hair cell degeneration. The
scientific environment, support from the Department of Otolaryngology at Indiana University and the
internationally renowned mentors together make this project feasible. These factors maximize the potential to
attain Dr. Nelson's long-term career goal of becoming an independent clinician-investigator and discovering
new targets to prevent or delay hair cell degeneration.

## Key facts

- **NIH application ID:** 10132291
- **Project number:** 5K08DC016034-05
- **Recipient organization:** INDIANA UNIVERSITY INDIANAPOLIS
- **Principal Investigator:** Rick F Nelson
- **Activity code:** K08 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $178,830
- **Award type:** 5
- **Project period:** 2017-04-01 → 2023-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10132291

## Citation

> US National Institutes of Health, RePORTER application 10132291, Genetically Mediated Hair Cell Degeneration in 3D Inner Ear Organoids (5K08DC016034-05). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10132291. Licensed CC0.

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