# UVB Induced TLR3 Mediated Changes in Keratinocyte Physiology

> **NIH NIH F30** · PENNSYLVANIA STATE UNIV HERSHEY MED CTR · 2021 · $44,577

## Abstract

Abstract
This proposal is a mentored training fellowship that combines clinical exposure and research efforts with an
integrated research and clinical training plan to ensure the PI’s transition to a research-focused dermatology
residency. The PI’s clinical and research interests are in the inflammatory and immune-related molecular
mechanisms of skin disease.
The research focus of this proposal investigates the role of UVB exposure in driving an epithelial to
mesenchymal (EMT)-like phenotype in normal human keratinocytes. This proposal will use 2D and 3D human
keratinocyte cell cultures, in vivo mouse models, and patient samples to test the overall hypothesis that UVB
exposure results in Toll-Like Receptor 3 (TLR3)-dependent activation of NF-κB, leading to an EMT-like
phenotype in keratinocytes through the induction of EMT-associated genes and MMP-9.
In Aim 1, we hypothesize that TLR3-mediated NF-κB activation is required for the UVB-induced EMT-like
morphologic change in keratinocytes. To test this, keratinocytes exposed to UVB or PIC in combination with
inhibition of NF-κB will be assayed for NF-κB-dependent signaling changes, EMT associated gene and protein
changes, and changes in keratinocyte morphology, migration, and invasion properties. We will use both WT
and TLR3KO mice as well as human patient samples of cutaneous squamous cell carcinoma and normal skin
to investigate the co-expression of NF-κB and TLR3 proteins in skin.
In Aim 2, we will test the hypothesis that TLR3 activation and subsequent NF-κB stimulation are required for
MMP-9 induction and activation following UVB exposure. Keratinocytes exposed to UVB or PIC in combination
with MMP-9 inhibition will be monitored for changes in morphology and alterations in migration and invasion
potential. The effect of UVB exposure on MMP-9 will also be studied in vivo using WT and TLR3KO mice.
This proposal challenges current understanding which focuses on UVB as a DNA-damaging agent and instead
investigates TLR3 as a sensor of UVB-induced cell damage and activator of inflammatory pathways that can
have profound effects on keratinocyte morphology and function. Our proposal is significant in that it will
advance the field of skin biology by increasing our understanding of UVB-mediated activation of the innate
immune system and skin tumorigenesis.

## Key facts

- **NIH application ID:** 10240474
- **Project number:** 5F30ES030260-03
- **Recipient organization:** PENNSYLVANIA STATE UNIV HERSHEY MED CTR
- **Principal Investigator:** Andrea M Schneider
- **Activity code:** F30 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $44,577
- **Award type:** 5
- **Project period:** 2019-09-01 → 2022-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10240474

## Citation

> US National Institutes of Health, RePORTER application 10240474, UVB Induced TLR3 Mediated Changes in Keratinocyte Physiology (5F30ES030260-03). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/10240474. Licensed CC0.

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