# Therapeutic potential for modulation of olfactory basal stem cells

> **NIH NIH R01** · DUKE UNIVERSITY · 2021 · $342,125

## Abstract

PROJECT SUMMARY/ABSTRACT
It is estimated that at least 12% of the population is affected by olfactory loss. Anosmia, the loss of olfactory
function, can be due to aging, prior infection, or injury, and there are currently no effective treatments. Although
etiologies may vary, evidence suggests that neurogenic exhaustion, or a failure to replace or maintain the
olfactory neuron population, underlies many olfactory disorders. The regulation of adult olfactory neurogenesis
is, therefore, an area of active research. Building upon recent successes permitting the purification and culture
of adult olfactory basal stem or progenitor cells (globose basal cells), and the identification of Polycomb
complexes in subsets of olfactory cells, this proposal asks whether and how Polycomb complex-mediated
epigenetic modifications influence neurogenesis and epithelial homeostasis in the olfactory epithelium.
Polycomb complexes are essential epigenetic regulators during development, but their roles in olfactory
maintenance and renewal have not been investigated. Using a culture model, chromosome
immunoprecipitation- DNA sequencing (ChIP-seq), as well as in vivo approaches, Aim1 will test the hypothesis
that Polycomb complexes regulate renewal and differentiation in the olfactory epithelium. In addition to defining
epigenetic regulation in basal cells, Aim2 will test the ability of basal stem cells to be used to repair olfactory
damage. This Aim will address a major translational question: can a cell-based therapy treat a sensorineural
anosmia? Because regenerating host neurons interfere with the assessment of functional recovery following
olfactory lesions in mice, we will employ a novel inducible anosmia mouse model, in which regenerating
neurons lack cilia, for testing therapeutic potential of engrafted cells. The experiments will combine histology,
electrophysiology and behavioral approaches to comprehensively evaluate basal cell engraftment into
inducible anosmia hosts. Also, this model will be used to directly test the effects of altering Polycomb
expression in donor cells. These studies, guided by important clinical problems lacking current treatments, will
use innovative multi-pronged approaches to define previously unexplored mechanistic controls of olfactory
renewal and differentiation, and will provide essential data to design cell-based therapy for sensorineural
olfactory losses secondary to damage or neurogenic exhaustion, such as presbyosmia.

## Key facts

- **NIH application ID:** 10176446
- **Project number:** 5R01DC016859-05
- **Recipient organization:** DUKE UNIVERSITY
- **Principal Investigator:** Bradley J Goldstein
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $342,125
- **Award type:** 5
- **Project period:** 2019-08-15 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10176446

## Citation

> US National Institutes of Health, RePORTER application 10176446, Therapeutic potential for modulation of olfactory basal stem cells (5R01DC016859-05). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10176446. Licensed CC0.

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