Biography

Main Research lines

• Role and regulation of DNA-RNA hybrids in telomere instability and the Alternative Lengthening of Telomeres
• Transcription-replication conflicts and genome instability

During my career I have been interested in understanding the mechanisms of genome instability, a hallmark of cancer cells, with a focus on transcription-replication conflicts and RNA-mediated telomere instability.

Our DNA is constantly being damaged due to the exposure to external sources of damage and the cell’s own metabolism. A major driven of genome instability and replication stress is the conflict between the replication and transcription machineries. We are interested in deciphering the molecular mechanisms that cells use to avoid these pathological consequences. I have contributed to work that identified several chromatin and repair factors that prevent genome instability associated with these collisions, including the FACT and SWI/SNF chromatin complexes, BRCA2, FANCD2 and key players of the DNA Damage Response, some of which are commonly mutated in cancer.

Telomeres are key regions for preserving genome stability and controlling replicative senescence. They are frequently affected in precancerous lesions, telomere biology disorders and aging-related diseases. Telomeric DNA-RNA hybrids may hinder telomere DNA replication but also play important roles in cancer cells that use a telomerase-independent pathway to elongate telomeres and gain immortality. Using molecular biology and proteomic approaches, our current work aims to gain insight into the mechanisms regulating DNA-RNA hybrids at telomeres, as well as identifying key factors controlling these structures in cancer cells that use different telomere maintenance mechanisms.

Projects

Principal Researcher

• Replication and post-replication signalling pathways Regulating R-loop-associated Telomere instability in human cells – RteRloop-101027467. Horizon 2020- Marie Skłodowska-Curie Actions (MSCA)-IF-2020. European Commission. 2021-2024.

Researcher (last 5 years)

• Función de la cromatina en la inestabilidad genómica asociada a transcripción. PID2022-138251NB-I00. Plan Estatal. PI: Aguilera-López, Andrés (Universidad de Sevilla). 2023-2026.
• Modificaciones de histonas y proteínas de unión a ARN en el origen de la inestabilidad genética. US-1258654. Proyectos I+D+i FEDER Andalucía. PI: Aguilera-López, Andrés; Luna-Varo, Rosa (Universidad de Sevilla). 2020-2022.
• ERC Started Grant. Metabolism of DNA secondary structures – MetDNASecStr.  European Research Council. PI: Vannier, Jean-Baptiste (MRC-LMS-Imperial College London). 2015-2021.
• Telomere Replication and Stability. Medical Research Council (MRC). PI: Vannier, Jean-Baptiste (MRC-London Institute of Medical Sciences). 2014-2020.
• ERC Advanced Grant. R-loops as a major modulator of transcription-associated recombination and chromatin dynamics – TARLOOP. European Research Council. PI: Aguilera-López, Andrés (Universidad de Sevilla). 2015-2020.