# Molecular Mechanism of UV Protection in Cutaneous Melanoma

> **NIH NIH R01** · WISTAR INSTITUTE · 2021 · $622,335

## Abstract

Project Summary
Ultraviolet radiation (UVR) from sunlight has been epidemiologically identified as a leading risk factor for
melanoma development. However, the mechanistic details of how sunlight UVR causes melanoma are still
being elucidated. Recent studies revealed tremendous amounts of UV-induced genetic mutations in
melanoma genomes compared to most other types of tumors. Furthermore, UV-induced mutagenesis
accelerates melanoma progression and recurrence. These studies highlighted the need to better
understand the molecular mechanisms protecting against environmentally UVR-induced mutagenesis, and
to delineate why they fail to work in melanoma, providing answers that could pave the way for personalized
prevention and treatment of this often-fatal illness. This project will meet this challenge, capitalizing on our
recent discovery of an autophagy modulator as a bona fide UV protector through distinct mechanisms and
its strong correlation with reduced melanoma risk. Our primary hypothesis is that reduced capacity of UV-
induced photolesion repair and adaptive skin pigmentation represents the main reasons of genetic instability
of melanoma cells and is responsible for melanoma predisposition. To test the hypothesis, we will first
dissect the mechanism by which UV-induced photolesion is repaired in melanocytes to provide UV
resistance (Aim 1), identify the mechanism governing UV-induced melanogenesis and pigmentation to
prevent UV penetration (Aim 2), and determine how and to what extent these mechanisms of action impact
UV sensitivity and neoplastic expansion of melanoma using inducible transgenic and humanized murine
models (Aim 3). These aims will be addressed using multidisciplinary innovative approaches that integrate
state-of-the-art genetic, biochemistry, live-cell imaging, and physiological assays in cells and in mice with
targeted mutations in UV resistance genes. Together, we anticipate that our studies will identify new UV-
protecting mechanisms that regulate melanoma disease penetrance and provide compelling in vivo
validation of a novel prognostic and predictive biomarker in melanoma.

## Key facts

- **NIH application ID:** 10294255
- **Project number:** 5R01ES029092-04
- **Recipient organization:** WISTAR INSTITUTE
- **Principal Investigator:** Chengyu Liang
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $622,335
- **Award type:** 5
- **Project period:** 2020-07-29 → 2023-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10294255

## Citation

> US National Institutes of Health, RePORTER application 10294255, Molecular Mechanism of UV Protection in Cutaneous Melanoma (5R01ES029092-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10294255. Licensed CC0.

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