# Post-Transcriptional Regulators of Epidermal Homeostasis and Neoplasia

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA, SAN DIEGO · 2021 · $370,202

## Abstract

Project Summary/Abstract
Background: Transcriptional mechanisms that regulate epidermal homeostasis have
been well established but recently we have discovered that post-transcriptional
mechanisms play prominent roles in maintaining epidermal self-renewal. We have
shown that the RNA helicase DDX6 is necessary to maintain epidermal self-renewal
through the mRNA degradation and translation pathway. By associating with specific
members of the translation pathway DDX6 binds to and mediates the translation of
self- renewal and proliferation transcripts to maintain self-renewal. DDX6 also
associates with mRNA degradation proteins to bind differentiation-inducing
transcripts to promote their degradation to prevent premature differentiation.
Objective/hypothesis: This proposal seeks to understand the regulation of
epidermal homeostasis and tumor initiation through post-transcriptional mechanisms.
We previously identified proteins associated with DDX6 and our objective is to
characterize the role of each protein in regulating epidermal growth, differentiation,
and progression to neoplasia as well as the mechanisms of action. Furthermore we
seek to determine the specific transcripts that DDX6 and its associated complexes
bind during homeostasis and tumor initiation.
Specific Aims: (1) To determine the role of DDX6 associated proteins on epidermal
homeostasis and tumor initiation and (2) to identify and characterize the transcripts
associated with DDX6 complexes.
Study Design: To study epidermal homeostasis in a more clinically relevant setting,
we generate 3-dimensionally intact human skin, containing human epidermal cells
(that have been permanently knocked down for either DDX6 or its associated
proteins) in the context of human dermal stroma and basement membrane,
regenerated on immune compromised mice. By using this model, we can perform
loss of function experiments on DDX6 and its associated proteins in regenerated
human skin to characterize their role in epidermal growth, differentiation, and
progression to neoplasia. We will also use CLIP- Seq to determine the RNAs
associated with DDX6 complexes during the progression from normal to neoplastic
epidermis.

## Key facts

- **NIH application ID:** 10161730
- **Project number:** 5R01AR072590-04
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN DIEGO
- **Principal Investigator:** GEORGE L SEN
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $370,202
- **Award type:** 5
- **Project period:** 2018-07-18 → 2023-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10161730

## Citation

> US National Institutes of Health, RePORTER application 10161730, Post-Transcriptional Regulators of Epidermal Homeostasis and Neoplasia (5R01AR072590-04). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10161730. Licensed CC0.

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