# Investigating the role of cell competition in epidermal development

> **NIH NIH K99** · ROCKEFELLER UNIVERSITY · 2021 · $49,572

## Abstract

PROJECT SUMMARY:
The skin forms an essential permeability barrier that protects internal organs and tissues from physical
damage, dehydration, pathogen invasion, and other harmful environmental stresses. Defective barrier function
is associated with a broad range of pathologies including chronic wounds, congenital diseases, epithelial
cancers, infection, and other inflammatory conditions. In order to understand the basis of these disease states,
it is vital to first understand the processes by which the epidermis forms during development.
The skin arises from a single layer of stem cell progenitors to become a functionally specialized, multi-layered
permeability barrier at birth via a process of rapid expansion and differentiation. What are the quality control
mechanisms that act to ensure tissue function is optimized during development in preparation for post-natal
life? A phenomenon known as cell competition has been proposed to act as a selection mechanism in rapidly
expanding tissues, whereby less fit “loser” cells are eliminated by fitter neighbouring “winner” cells. The extent
to which cell competition acts as a conserved regulator of tissue and organ growth is unknown. This study sets
out to test the hypothesis that in the mammalian skin, cell competition provides an essential quality control
mechanism during development to safeguard the tissue against stresses in both pre- and post-natal life.
Using a unique combination of genetic tools available in the mouse, the proposed work employs a combination
of cell biology, lineage tracing and computational approaches to uncover evidence for cell competition during
epidermal development (Aim 1). Furthermore, building on a newly established system to experimentally induce
cell competition, functional genetics and quantitative live imaging will be used to dissect the genetic regulation
of cell competition (Aim 2). Finally, using functional assays, the proposed experiments examine the
consequence of disrupting cell competition during development on the ability of the skin to carry out its
essential barrier function (Aim 3). The expected results will (a) establish a new paradigm and generate genetic
tools to study mammalian cell competition; (b) offer new perspective on spatiotemporal control of early
epidermal development; (c) shed light on the molecular underpinnings of cell competition, which may be
exploited therapeutically in the long term to treat a broad range of barrier pathologies. Under the supervision of
leading epidermal cell biologist, Dr. Elaine Fuchs, the co-mentorship of cell competition expert, Dr. Laura
Johnston, and the stimulating training environment at the Rockefeller University, I am ideally positioned to fully
develop my technical skills, knowledge, and leadership. My research, training, and career development will
allow me to establish a unique research niche in epidermal and developmental biology as an independent
investigator.

## Key facts

- **NIH application ID:** 10405355
- **Project number:** 3K99AR074557-02S2
- **Recipient organization:** ROCKEFELLER UNIVERSITY
- **Principal Investigator:** Stephanie Ellis
- **Activity code:** K99 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $49,572
- **Award type:** 3
- **Project period:** 2021-08-01 → 2022-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10405355

## Citation

> US National Institutes of Health, RePORTER application 10405355, Investigating the role of cell competition in epidermal development (3K99AR074557-02S2). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10405355. Licensed CC0.

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