# REGULATION OF SKIN HOMEOSTASIS BY RNA-BINDING PROTEINS

> **NIH NIH K01** · STANFORD UNIVERSITY · 2024 · $123,093

## Abstract

REGULATION OF SKIN HOMEOSTASIS BY RNA-BINDING PROTEINS
 PROJECT SUMMARY/ABSTRACT
 One in four Americans are affected by skin disease, intensely motivating an understanding on the mechanisms
underlying epidermal homeostasis. RNA-binding proteins (RBPs) and the main arginine methyltransferase
PRMT1 are required for the control of keratinocyte proliferation and differentiation. We have identified two
nucleolar RNA helicases and multiple PRMT1 targets that are required for normal skin homeostasis. We have
also identified PRMT1 itself is an RBP. A long-term goal of my research is to understand homeostatic
mechanisms in skin; the goal of this K01 application is to characterize the roles of RBPs in epidermal
homeostasis, specifically the two helicases, PRMT1 and PRMT1 target RBPs.
 In Aim I, we will test our model for PRMT1’s maintenance of the progenitor state in keratinocytes. Our
preliminary data indicates that five stable RBP interactors of PRMT1 – which are also targets of its
methyltransferase activity – are also required to maintain homeostasis. In Aim IA, we test the consequence of
arginine methylation on these RBPs. In Aim IB, we test the effect of these RBPs and their methylation on gene
expression in keratinocytes.
 In Aim II, we test our model for how RNA helicases promote keratinocyte differentiation. Our data suggests
two helicases are sequence-specific, pre-mRNA-binding proteins that promote differentiation by departing the
nucleolus to regulate splicing and potentially transcription. Our results also suggest that these helicases can
form homo- and heterodimers, with the heterodimer being the strongest interaction. In Aim IIA, we will test their
role in transcriptional control of keratinocyte differentiation and whether their apparent control of splicing is direct.
In Aim IIB, we will evaluate their dimerization state and its relation to their role in homeostasis, splicing and
transcription.
 My background is in RBP biochemistry, bioinformatics, methods development, and CLIP-seq. Over the course
of the training period and within the environment of Stanford’s Department of Dermatology, I plan to acquire
expertise in (1) epithelial biology, (2) proteomics, (3) machine learning, and (4) statistics. My research interest in
skin biology requires this broad skill set, and this research plan will prepare me for an independent career as an
academic scientist working on the mechanisms of gene regulation in epithelial tissue.

## Key facts

- **NIH application ID:** 10827472
- **Project number:** 5K01AR082351-02
- **Recipient organization:** STANFORD UNIVERSITY
- **Principal Investigator:** Douglas F Porter
- **Activity code:** K01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $123,093
- **Award type:** 5
- **Project period:** 2023-05-01 → 2026-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10827472

## Citation

> US National Institutes of Health, RePORTER application 10827472, REGULATION OF SKIN HOMEOSTASIS BY RNA-BINDING PROTEINS (5K01AR082351-02). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10827472. Licensed CC0.

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