Unveiling the Genetic Landscape of UV-Induced Cellular Responses: A CRISPR Whole Genome Screening Approach

• Applicants: Privatdozent Dr. Thomas Haarmann-Stemmann; Andrea Rossi, Ph.D.
• Subject Area: Dermatology ; Toxicology, Laboratory Medicine
• Term: since 2025
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 566960894

Skin diseases are the fourth most common cause of all human disease, affecting nearly one‐third of the world’s population. An important environmental factor involved in the development and/or exacerbation of a broad variety of cutaneous diseases is ultraviolet (UV) radiation. In fact, despite the beneficial effects associated with low everyday exposure (vitamin D synthesis), excessive exposure to solar or artificial UV radiation may cause adverse health effects, including skin carcinogenesis. Understanding the intricate interplay between UV radiation exposure and cutaneous cellular responses is crucial for developing effective strategies to protect against and treat UV radiation-induced diseases and disorders of the skin. Traditionally, identifying the genetic factors that influence cutaneous UV sensitivity or resistance relied on laborious and time-consuming forward genetics approaches. However, these methods often lacked the comprehensiveness and precision required to fully unravel the genetic landscape of UV-mediated cellular responses. The emergence of CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats) technology has revolutionized genetic research by providing a powerful tool for the rapid and systematic identification of genes essential for specific cellular processes. By harnessing a comprehensive library of sgRNAs (single guide RNAs) designed to target every gene within the human genome, we aim to undertake a systematic and exhaustive evaluation of the functional role that each individual gene plays in modulating UV-mediated cellular responses. In this research project, we will employ both positive and negative selection strategies within the CRISPR/Cas9-based genetic screens to gain comprehensive insights into the genetic determinants that govern cellular responses to specific stressors, in particular UV light exposure. Importantly, a subset of identified genes will undergo rigorous validation and functional characterization in primary keratinocytes and iPSC-derived skin organoids (induced Pluripotent Stem Cells), bridging the gap between laboratory findings and clinical applications. Through the systematic identification of genes and pathways involved in resistance and susceptibility towards UV irradiation, our research aims to advance our understanding of disease mechanisms, develop targeted therapeutic interventions, and pave the way for personalized medicine approaches tailored to the individual genetic profile. Ultimately, by unraveling the complex genetic landscape governing UV sensitivity and resistance, we aspire to enhance skin health, mitigate the adverse effects of UV radiation exposure, and revolutionize dermatological care.

• DFG Programme: Research Grants