Elena Llano Cuadra

After receiving a Ramón y Cajal contract in the 2007 call, I joined the Department of Physiology and Pharmacology at the University of Salamanca where I recently attained the position of Full Professor at this University . Since then, I have been conducting scientific research and teaching. In collaboration with Dr. Alberto M. Pendás of the Cancer Research Center of Salamanca, we have embarked on a new research direction focused on chromosomal segregation, gametogenesis, and fertility. Our work has yielded significant contributions, as evidenced by our list of publications. Among our findings, we have determined the crucial role of the Sgol2 protein in maintaining centromeric cohesion during meiosis, ensuring the production of functional gametes. Additionally, we have characterized a novel subunit of the meiosis-specific cohesin complex, Rad21L, which, when deficient, causes non-obstructive azoospermia (NOA) in males and premature ovarian failure (POF) in females. Through exome sequencing analysis of an inbred family with POF, we identified a 1-bp homozygous deletion in the STAG3 gene, resulting in a premature stop codon. By modeling this condition in mice, we established, for the first time, a cause-and-effect relationship between the cohesin complex subunit STAG3 and human infertility. More recently, our research has revealed that an anonymous locus described in a GWAS study on human infertility is a critical component of the synaptonemal complex (SIX6OS1), essential for fertility in both males and females. Furthermore, we have demonstrated that the multivalent interactions between SYCE1 and SIX6OS1 are vital for synapsis and are disrupted in cases of human infertility. Our investigations have also explored the involvement of the ubiquitin proteasome system (UPS) in meiosis through the USP26 protease, as well as the role of the testicular-specific proteasome (spermatoproteasome, PSMA8) in protein degradation pathways. PSMA8 is localized in and dependent on the central region of the synaptonemal complex (SC). Consequently, PSMA8-deficient mice exhibit disruptions in proteostasis among key meiotic players, leading to apoptotic spermatocytes. In our studies on hereditary infertility, we have identified RAD51B, along with the new meiotic players HSF2BP and BREM1, as mutated POI genes through next-generation sequencing (NGS) analysis. Additionally, we have demonstrated that the recurrent variant C134W, affecting the transcription factor FOXL2, is a key driver in the development of ovarian granulosa cell tumors. Very recently we have introduce RNF212B, a novel E3 ubiquitin ligase, as a crucial player involved in CO licensing and designation in a DSB-independent and synapsis-dependent manner ultimately influencing mouse fertility. Currently, our research focuses on the comprehensive investigation of male and female gametogenesis processes using murine models generated with the CRISPR/Cas9 technique. By doing so, we aim to identify novel genes and gene variants that play significant roles in these processes. Ultimately, understanding the alterations in these genes will contribute to the elucidation of pathologies such as infertility.