# Restoring Melanocyte Stem Cells: A Model of Drug-Mediated Regeneration

> **NIH NIH R56** · UNIVERSITY OF ALABAMA AT BIRMINGHAM · 2020 · $299,411

## Abstract

Project Summary
Increasing the length of time an individual experiences good health, or a healthy life expectancy, can be
achieved by recovering tissue function that is lost or impaired due to aging or disease. Exploiting endogenous
stem cells to repair or replace tissues in situ is an ideal approach to harness a body’s innate potential for
rejuvenation. Unlike exogenous stem cells, using endogenous stem cells for regenerative medicine reduces
the need for complicated, ex vivo cellular reprogramming and tissue engineering protocols, and eliminates the
risk of rejection. Outside of the hematopoietic system, however, few examples exist where stem cell function is
enhanced in situ for therapeutic purposes within the clinic. One reason for this is that although much is known
about regulatory pathways that guide physiological stem cell function, much less is known about the minimum
cellular and systemic requirements for tissue rejuvenation when the stem cell pool is damaged or absent. In
addition, few pharmacological modulators have been identified to allow us to investigate this question in situ.
Here we describe preliminary evidence demonstrating that we can reverse hair graying associated with
melanocyte stem cell loss in mice using the novel drug RT1640. Hair graying and melanocyte stem cells are an
ideal model for investigating tissue rejuvenation. Melanocyte stem cells reside in the hair follicle and are
responsible for regenerating the pigment system and hair shaft pigmentation during hair growth. Gray hair due
to loss of melanocyte stem cell function is both visible and non-lethal, melanocyte stem cell activation can be
induced experimentally by simply plucking the hair, and this stem cell population is responsive to non-invasive
therapeutics applied topically to the skin. Using this model, the aims of this proposal will address unanswered
questions regarding pharmacologically induced in-situ tissue rejuvenation. Namely, we will identify the
minimum biological elements necessary for in vivo repair, the critical cell types that participate in the
regenerative response, and the key molecular processes targeted by this regenerative drug. We will answer
these questions using a variety of hair graying mouse models with known molecular defects, in vivo fate
mapping, and an in vitro histoculture method. These studies will provide a valuable new example of how tissue
rejuvenation can be achieved through an in-situ approach, with significant relevance to understanding
mechanisms involved in reversing the effects of disease and aging in humans.

## Key facts

- **NIH application ID:** 10253127
- **Project number:** 1R56AG066740-01
- **Recipient organization:** UNIVERSITY OF ALABAMA AT BIRMINGHAM
- **Principal Investigator:** Melissa L Harris
- **Activity code:** R56 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $299,411
- **Award type:** 1
- **Project period:** 2020-09-30 → 2022-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10253127

## Citation

> US National Institutes of Health, RePORTER application 10253127, Restoring Melanocyte Stem Cells: A Model of Drug-Mediated Regeneration (1R56AG066740-01). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10253127. Licensed CC0.

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