# Bidirectional control of keratinocyte differentiation and proliferation by transcription factor FOXQ1

> **NIH NIH R01** · DUKE UNIVERSITY · 2024 · $485,781

## Abstract

The skin forms the first barrier against physical, biological and chemical insults and is essential for prevention
of dehydration. To maintain this function epidermal keratinocytes undergo differentiation. During differentiation,
the gene expression programs in keratinocytes switch from maintenance of cell proliferation to terminal
differentiation. Calcium gradient formed between the basal and upper epidermal layers is a major factor
underlying induction of terminal differentiation in keratinocytes. In addition, skin homeostasis relies on well-
orchestrated intercellular communications mediated by cytokines that are produced by keratinocytes and other
skin resident cells.
 We have identified that transcription factor FOXQ1 (a member of the Forkhead Box family of proteins) utilizes
a novel, rheostat-like mechanism of transcriptional regulation of keratinocyte differentiation. Thus, in presence
of low extracellular calcium, FOXQ1 repressed genes associated with epidermal differentiation in normal human
keratinocytes (NHKs) and immortalized human keratinocytes (HaCaT). On the contrary, in calcium-treated (i.e.
differentiation-induced) NHK and HaCaT cells, FOXQ1 activated the same set of genes. Therefore, in Specific
Aim 1, we will identify the mechanisms underlying transcriptional regulation by FOXQ1 of keratinocyte
differentiation.
 In addition, we demonstrated that under normal conditions, depletion of FOXQ1 in cultured keratinocytes
decreased whereas its overexpression increased cell proliferation. Moreover, Foxq1-/- mice demonstrated
decreased epidermal hyperplasia in response to treatment with imiquimod which induces psoriasis-like
phenotypes in mouse epidermis.
 Therefore, in Specific Aim 2, we will generate keratinocyte-specific Foxq1 knock-out mice and identify the
mechanisms of FOXQ1 regulation by pro-inflammatory cytokines and the role of Foxq1 in regulation of
keratinocyte hyper-proliferation.

## Key facts

- **NIH application ID:** 10894896
- **Project number:** 5R01AR082911-02
- **Recipient organization:** DUKE UNIVERSITY
- **Principal Investigator:** Mikhail Nikiforov
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $485,781
- **Award type:** 5
- **Project period:** 2023-08-01 → 2028-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10894896

## Citation

> US National Institutes of Health, RePORTER application 10894896, Bidirectional control of keratinocyte differentiation and proliferation by transcription factor FOXQ1 (5R01AR082911-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10894896. Licensed CC0.

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