Transposable Elements in Development and in Disease

• Identification of new functions of endogenous retroviruses during development using zebrafish as a model.
• Role of human specific endogenous retroviruses during embryonic development (HERVs) and in developmental pathologies (22q11 deletion syndrome; 22qDS) using genome-edited hESCs.
• Analysis of the IFN response activation mediated by TEs in rare diseases and age-associated diseases.

Both the functions of TEs during embryonic development and the activation of the major antiviral innate immune pathway, the type I interferon (IFN) response, by endogenous TE expression, has emerged as a new and exciting field in biomedicine being documented by the more prestigious journals in the last few years. However, there is controversy regarding the type of TEs and the biological functions they have at different developmental stages, as well as the nature of the TE-derived nucleic acids responsible for stimulating IFN production in such important pathological processes as cancer, senescence and autoimmune diseases. Therefore, implementing and developing experimental and computational approaches to analyze the molecular mechanisms underlying the functions of TEs will provide wholly new perspectives to our understanding of various diseases.

Haploinsufficiency of DGCR8 contributes to the human 22q11.2DS, whereas mutations inactivating DGCR8 function are considered drivers of tumors, including the pediatric Wilm’s tumor. This research line could identify new therapeutic targets leading to the development of treatments for patients with 22q11DS. In addition, I am the director of the «Aula de Estudios del Síndrome de deleción 22q11.2» which ensures the transfer of the knowledge generated to the Society. On the other hand, considering that TEs can activate the interferon response in tumor cells and agerelated diseases, our research could provide new therapeutic target for some types of tumors and for alleviating human aging-related disorders. Finally, I am a member of the EU-funded Andalucía Biotec Salud Biomodels Platform, which aims to develop disease diagnostic tools and advanced therapies.

Apply for ERC Synergy Grant (EU) in collaboration on the dual role of TEs on miRNA synthesis pathway mutations-driven tumors: impact of insertions vs IFN activation.