My research interests have focused on transcription and replication as main sources of genetic instability. During my PhD, I worked with Prof. Andrés Aguilera on transcription, and R-loops in particular, as a source of genetic instability. My PhD, funded by an FPU fellowship, was awarded in 2009 with ‘Sobresaliente Cum Laude’, European Mention, and later on awarded with the ‘Premio Extraordinario de Doctorado’. I development powerful genetic tools for the identification of R-loops in vivo by the heterologous over-expression of human AID in yeast mutants of the THO complex, involved in mRNP biogenesis. I also contributed to show that co-transcriptional R-loops impair replication fork progression and identified that as the main cause of transcription-associated genetic instability. I further showed that the phenotypes of THO mutants could be observed genome-wide. In agreement with R-loops being a frequent source of DNA damage, I showed that to survive replication stress, THO mutants require a functional S-phase checkpoint, known to be essential for the maintenance of replication fork stability.
I then decided to deepen my understanding of the replication process with a leading scientist in the field, Dr. John Diffley. For this purpose, I moved to UK in 2010 and worked at Clare Hall Laboratories (belonging to CRUK until April 2015 and to The Francis Crick Institute since then), where I was funded by a long-term EMBO Fellowship and by CRUK to work on the role of S-phase checkpoints in replication fork stabilization. Combining genome-wide sequencing with the power of classical genetics, I defined an unexpected link between histone deacetylation and fork stability. Further mechanistic insights allowed us to uncover the role of certain factors in irreversible fork arrest both in yeast and human cells.
In 2015, I was awarded a grant from the Spanish Association Against Cancer (AECC) and I re-joined Andrés Aguilera´s laboratory in CABIMER to work on the consequences of R-loops and transcription in general on replication forks. Since then, I am working on the mechanisms that might explain R-loop accumulation in human cells, in particular in BRCA2 deficient cells and its connection not only with the replication fork but also with other BRCA2-related functions, such as homologous recombination and mitosis. In parallel, I am working in the identification of new genes involved in the prevention or resolution of R-loops. During this time, I have supervised two Erasmus projects, and I am supervising two PhD projects, one focusing on the role of histone deacetylases in the repair of replication-born DNA breaks and the other one investigating the use of new methodologies to map R-loops genome-wide and screening for histone factors that can be involved in the prevention of R-loop accumulation.