Dr. Águeda M. Tejera   agueda.tejera@ufv.es

Dr. María Jesús Delgado Martos

Dr. Maria Blasco (Centro Nacional de Investigaciones Oncológicas, CNIO)
Dr. Blanca López-Íbor (Hospital HM Montepríncipe)

Marta Osuna, MD (Hospital HM Montepríncipe, Fellow Jerôme Lejeune and Álvaro Entrecanales Foundations)
Eva Galián Guevara

Eva Galián Guevara (End-of-Master’s-Degree) Project
Adrián Martínez Fernández (Biomedicine)

RESEARCH LINE
Biological processes related to aging with a translational perspective, through the development of gene therapy for diseases that trigger premature aging of the organism.

Advances in the field of biomedicine, reflected in the early diagnosis of diseases and the development of efficient and specific therapies, have contributed significantly to an increase in life expectancy. Concomitantly, pathologies associated with aging have gradually increased. These deleterious changes associated with the natural aging process sometimes manifest themselves at an early age due, in this case, to congenital alterations that trigger genetic diseases of varying degrees of severity. The study of genes and biological processes whose alterations lead to these pathologies with molecular and physiological bases in common with the natural aging process can constitute a source of knowledge that can contribute both to the treatment of these diseases and to the delay or improvement of those physiological processes associated with the aging of the organism. In particular, we have focused on dyskeratosis congenita and the resistance shown to certain types of tumors in patients with Down syndrome. Furthermore, a better understanding of the biology of aging can contribute to improving the quality of life of our elders and, therefore, of society.

Moreover, this translational perspective of our research implies the development of safer and more efficient therapeutic strategies. Currently, viral vectors are the gene transfer systems of choice in gene therapy clinical trials, due to their greater effectiveness and lower toxicity compared to non-viral systems. Specifically, adeno-associated virus (rAAV)-derived vectors due to their low immunogenicity, high capacity to infect high and low dividing cells, high transduction efficiency and long expression of the therapeutic gene.

Moreover, in the last two decades, aptamers have emerged as a new system for specific recognition of target molecules, with a wide potential in their application as biosensing, diagnostic and therapeutic elements. The chemical binding of these aptamers to the viral capsid allows specific recognition of cellular receptors recognized by the specific aptamer. To this end, another important line of research of our group consists of generating viral vectors with high therapeutic selectivity, by means of a mixed strategy of genetic and chemical manipulation of parvoviruses in search of a tropism directed towards a specific cellular target.

The research lines of the group also have a strong ethical component; we are firmly convinced that it is necessary a powerful research in diseases that due to lack of effective and safe therapies put at risk the lives of people, in their different stages, and in this way we could contribute to the welfare of our society.

• AUTHOR=Osuna-Marco Marta P., Martín-López Laura I., Tejera Águeda M., López-Ibor Blanca TITLE=Questions and answers in the management of children with medulloblastoma over the time. How did we get here? A systematic review JOURNAL=Frontiers in Oncology VOLUME=13 YEAR=2023 URL=https://www.frontiersin.org/articles/10.3389/fonc.2023.1229853 DOI=10.3389/fonc.2023.1229853

• “Ten Reasons Why People With Down Syndrome are Protected From the Development of Most Solid Tumors -A Review “.Osuna-Marco MP, López-Barahona M, López-Ibor, Tejera AM. Frontiers in Genetics. 2021. Vol 12, doi: 10.3389/fgene.2021.749480

• “A synthetic mRNA cell reprogramming method using CYCLIN D1 promotes DNA repair generating improved genetically stable human induced pluripotent stem cells”. Alvarez-Palomo AB, Requena-Osete J, Delgado-Morales R, Moreno-Manzano V, Grau-Bove C, Tejera AM, Otero MJ, Barrot C, Santos-Barriopedro I, Vaquero A , Mezquita-Pla J, Moran S, Hobeich Naya C, Garcia-Martínez I, Vidal Pérez F, Blasco MA, Esteller M, Edel MJ. Stem Cells. 2021 Feb 23, doi: 10.1002/stem.3358

• “TPP1 is required for TERT recruitment, telomere elongation during nuclear reprogramming, and normal skin development in mice.” Tejera AM, Stagno d’Alcontres M, Thanasoula M, Marion RM, Martinez P, Liao C, Flores JM, Tarsounas M, Blasco MA. Dev Cell. 2010 May 18;18(5):775-89.

• “Generation of mice with longer and better preserved telomeres in the absence of genetic manipulations.” Varela E, Muñoz-Lorente MA, Tejera AM, Ortega S, Blasco MA. Nat Commun. 2016 Jun 2;7:11739.

• “Therapeutic effects of telomerase in mice with pulmonary fibrosis induced by damage to the lungs and short telomeres.” Povedano JM, Martinez P, Serrano R, Tejera Á, Gómez-López G, Bobadilla M, Flores JM, Bosch F, Blasco MA. Elife. 2018 Jan 30;7:e31299.

• “AAV9-mediated telomerase activation does not accelerate tumorigenesis in the context of oncogenic K-Ras-induced lung cancer.” Muñoz-Lorente MA, Martínez P, Tejera Á, Whittemore K, Moisés-Silva AC, Bosch F, Blasco MA. PLoS Genet. 2018 Aug 16;14(8):e1007562.

• “Impact of a Multichannel Blocker in Attenuating Intramyocardial Artery Remodeling in Hypertensive Rats through Increased Nitric Oxide Bioavailability.” Quintana-Villamandos B, Delgado-Martos MJ, Delgado-Baeza E. Biomed Res Int. 2019 Jul 2;2019:6374582.

• “Early reversal cardiac with esmolol in hypertensive rats: The role of subcellular organelle phenotype.” Quintana-Villamandos B, Delgado-Martos MJ, Delgado-Baeza E. Pharmacol Rep. 2019 Dec;71(6):1125-1132.

·”Differential protection against medulloblastoma in children with Down syndrome as a basis for an antitumor therapy based on miRNAs” (2022-2023). PI: Águeda M. Tejera. Funding: Universidad Francisco de Vitoria.

· “Manipulation of the tropism of Parvovirus-derived viral vectors through their association to cell receptor-selective binding aptamers”. (2021-2022) PI: Cristina Sánchez. Funded by: Universidad Francisco de Vitoria.

· “Study of telomeric dysfunction caused by TIN2 deficiency and rescue by gene editing as a possible therapy for telomeropathies.” (2020-2021). PI: Águeda M. Tejera Funding: Universidad Francisco de Vitoria.