PERSONAL

LEAD RESERCHER:

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

RESERCHERS:

Dr. Cristina Sánchez Martínez
Dr. María Jesús Delgado Martos

EXTERNAL COLLABORATING RESEARCHERS:

Dr. Maria Blasco (Centro Nacional de Investigaciones Oncológicas, CNIO)
Dr. Víctor M. González (Instituto Ramón y Cajal de Investigación Sanitaria, IRYCIS)

PRE-DOCTORAL RESEARCHERS:

Marta Osuna, MD (Hospital HM Montepríncipe, Internship at Fundaciones Jerôme Lejeune y Álvaro Entrecanales) Ignacio Escrig Larena (Final project student, Double Degree in Biotechnology + Pharmacy)

OUTLINE OF RESEARCH:

Advances in biomedicine, resulting in the early diagnosis of illnesses and the development of effective, specific treatments, has made a significant contribution in extending human life. In parallel, there has been a gradual increase in pathologies associated with ageing. These deleterious changes, associated with the nature aging process, can appear at an early age due, in this case, to congenital alterations which trigger genetic illnesses of varying degrees of severity. The study of genes and biological processes, the alterations of which lead to pathologies sharing the same molecular and physiological origins as the natural aging process, may provide a wealth of knowledge for both the treatment of these pathologies as well as the delaying or improvement of the physiological processes associated with the aging process. We have focussed our research particularly on congenital dyskeratosis and the resistance shown by certain types of tumours in patients with Down syndrome. Furthermore, a better understanding of the biological process of aging may contribute to improved quality of life for our elderly and for society as a whole.

In addition, the translational approach of our research implies the development of safer and more efficient therapeutic strategies. Currently, viral vectors constitute the delivery system of choice in clinical testing of gene therapy due to its greater effectiveness and lesser toxicity than other, non-viral methods. Specifically, recombinant adeno-associated viral (rAAV) vectors due to their low immunogenicity, high capacity to infect cells in high and low degree of division, highly effective transduction and long expression of the therapeutic gene.

Additionally, in the last two decades aptamers have become a new system for the specific identification of target molecules with broad possible applications as biosensors, in diagnosis and treatment. The chemical union of these aptamers to the viral capsid permits the specific identification of cellular receptors recognised by the specific aptamer. Thus, another important line of research for our Group consists in generating viral vectors with high therapeutic selectivity through a mixed strategy of genetic and chemical manipulation of parvovirus for tropism aimed at a specific target cell.

The research lines of the group also contain a pronounced ethical commitment: we firmly believe it is necessary to conduct thorough research into illnesses which, due the absence of safe and effective treatment, put people’s lives at risk at different stages of life and in this way contribute to the betterment of our society.

PROJECTS:

Research Project funded by the Francisco de Vitoria University entitled “Study of telomeric dysfunction caused by TIN2 deficiency and recovery through gene editing as a possible treatment for telomeropathies.” (2020-2021)

PUBLICATIONS RELATED TO THE LINE OF RESEARCH:

• “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.

• “Essential role of the unordered VP2 n-terminal domain of the parvovirus MVM capsid in nuclear assembly and endosomal enlargement of the virion fivefold channel for cell entry.” Sánchez-Martínez C, Grueso E, Carroll M, Rommelaere J, Almendral JM. Virology. 2012 Oct 10;432(1):45-56.

• “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.

• “Antiangiogenic Vascular Endothelial Growth Factor-Blocking Peptides Displayed on the Capsid of an Infectious Oncolytic Parvovirus: Assembly and Immune Interactions.” Grueso E, Sánchez-Martínez C, Calvo-López T, de Miguel FJ, Blanco-Menéndez N, Fernandez-Estevez M, Elizalde M, Sanchez J, Kourani O, Martin D, Tato A, Guerra M, Andrés G, Almendral JM. J Virol. 2019 Sep 12;93(19):e00798-19.

• “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.