Natalia Cestari Moreno, Ph.D.

Dr. Natalia Cestari Moreno is a Research Assistant Professor in the Department of Cancer Biology at the University of Kansas Medical Center. She earned her Ph.D. in Genetics from the University of São Paulo, Brazil, where she investigated how UVA-induced oxidative stress promotes DNA damage, mutagenesis, and genome instability in Xeroderma Pigmentosum Variant (XP-V), a rare DNA repair disorder associated with extreme sensitivity to sunlight and a high risk of skin cancer. These studies revealed the critical role of DNA polymerase eta (Pol η) in protecting cells from oxidative DNA damage and replication stress.
To further understand how DNA polymerase eta (Pol η) protects cells from UVA-induced oxidative stress and genome instability, Dr. Moreno completed postdoctoral training at the University of São Paulo and the National Institutes of Health (NIH). Building on her doctoral studies in XP-V, she investigated the molecular mechanisms that regulate Pol η function during DNA damage tolerance, with a particular focus on post-translational modifications, including ubiquitination and NEDDylation, and the protein interaction networks that coordinate cellular responses to DNA damage and replication stress.
Dr. Moreno's current research seeks to define how oxidative stress, replication stress, and DNA repair pathways interact to maintain genome stability following UVA exposure. Her research investigates how defects in DNA damage tolerance mechanisms trigger persistent oxidative stress, impair DNA repair capacity, and promote mutagenesis and cancer development. By integrating molecular, cellular, proteomic, and genomic approaches, her work aims to identify the signaling networks that connect replication stress, redox imbalance, and genome instability, with the long-term goal of developing strategies to prevent and mitigate sunlight-induced carcinogenesis.
Dr. Moreno also serves as Co-Chair of the Student and Early Career Investigator (SECI) Committee of the Environmental Mutagenesis and Genomics Society and is actively engaged in mentoring, scientific outreach, and professional development initiatives within the fields of mutagenesis, DNA repair, and genome stability.

The integrity of the genome is continuously challenged by endogenous metabolic processes and environmental agents that generate DNA damage. Among these threats, oxidative stress caused by reactive oxygen species (ROS) is a major driver of genome instability, particularly in tissues exposed to solar ultraviolet radiation (UVR), chronic inflammation, and certain chemotherapeutic agents. Oxidative DNA damage can disrupt DNA replication, impair DNA repair pathways, and promote the accumulation of mutations that contribute to aging, cancer, and other human diseases.
Our research seeks to understand how cells maintain genome stability under conditions of oxidative stress and how failures in these protective mechanisms drive disease. We are particularly interested in the interplay between DNA damage tolerance, replication stress, and DNA repair pathways that preserve genome integrity following UVA-induced oxidative damage. A major focus of our work is DNA polymerase eta (Pol η), a specialized translesion synthesis (TLS) polymerase that enables cells to replicate damaged DNA and whose deficiency causes Xeroderma Pigmentosum Variant (XP-V), a rare genetic disorder associated with extreme sunlight sensitivity and a dramatically elevated risk of skin cancer.
Using patient-derived cells and advanced cellular models, we investigate how oxidative stress influences DNA repair capacity, replication dynamics, and stress-response signaling networks. Our studies explore the molecular mechanisms that regulate Pol η and related genome maintenance factors, including post-translational modifications, protein interaction networks, and redox-dependent signaling pathways. We are also interested in understanding how persistent replication stress and oxidative damage amplify genome instability and contribute to carcinogenesis.
To address these questions, we combine molecular, cellular, proteomic, and genomic approaches, including DNA repair and replication assays, chromatin-based analyses, cell cycle profiling, proteomics, and controlled oxidative stress systems such as UVA irradiation and chemoptogenetic tools. Our long-term goal is to define the mechanisms that connect oxidative stress, replication stress, and DNA repair failure, ultimately identifying new strategies to prevent mutagenesis, reduce cancer risk, and improve outcomes for individuals affected by DNA repair disorders.

ATR/Chk1 Pathway is Activated by Oxidative Stress in Response to UVA Light in Human Xeroderma Pigmentosum Variant Cells.

DNA polymerase η is regulated by mutually exclusive mono-ubiquitination and mono-NEDDylation.

How do Translesion Polymerases deal with Photodamage?

The key role of UVA-light induced oxidative stress in human Xeroderma Pigmentosum Variant cells.

Whole-exome sequencing reveals the impact of UVA light mutagenesis in xeroderma pigmentosum variant human cells.