Mouse Genome Editing Core Unit

Sagrario Ortega Head of Unit
T +34 917328000 (Ext 3170)
sortega@cnio.es

Technicians

Beatriz Escobar
Carmen Gómez
Jaime Muñoz
Patricia Prieto
Pierfrancesco Vargiu

The term “cancer” encompasses a whole spectrum of extremely complex diseases. Genetic and epigenetic modifications in tumour cells lead to the acquisition of a “malignant” phenotype that enables them to escape normal physiological control. We can accurately reproduce many of these modifications in the mouse, creating animal models to study the disease. Tumour cells also interact, at different levels, with other cells in the body such as those of the tumour stroma, immune, cardiovascular or lymphatic systems, which, in turn, modulate tumour growth, invasion and expansion. The study of such complexity requires in vivo models that reproduce all the features of cancer in a “whole body” context, including the specific genetic alterations that lead to tumour development in each particular tumour. The precise, targeted and controlled modification of the mouse genome, using the most advanced genome editing tools, sustains the generation of genetic mouse models of cancer that are crucial for understanding the molecular basis of tumour development and the preclinical validation of new and more efficient cancer therapies.

Publications

Miguel V, Tituaña J, Herrero JI, Herrero L, Serra D, Cuevas P, Barbas C, Puyol DR, Márquez-Expósito L, Ruiz-Ortega M, Castillo C, Sheng X, Susztak K, Ruiz-Canela M, Salas-Salvadó J, González MAM, Ortega S, Ramos R, Lamas S (2021). Renal tubule Cpt1a overexpression protects from kidney fibrosis by restoring mitochondrial homeostasis. J Clin Invest 131, e140695. CNIO Publication.
Olmeda D, Cerezo-Wallis D, Mucientes C, Calvo TG, Cañón E, Alonso-Curbelo D, Ibarz N, Muñoz J, Rodriguez-Peralto JL, Ortiz-Romero P, Ortega S, Soengas MS. (2021). Live imaging of neolymphangiogenesis identifies acute antimetastatic roles of dsRNA mimics. EMBO Mol Med 13, e12924. CNIO Publication. Open Access
Salmón M, Paniagua G, Lechuga CG, Fernández-García F, Zarzuela E, Álvarez-Díaz R, Musteanu M, Guerra C, Caleiras E, Muñoz J, Ortega S, Drosten M, Barbacid M (2021). KRAS4A induces metastatic lung adenocarcinomas in vivo in the absence of the KRAS4B isoform. Proc Natl Acad Sci USA 118, e2023112118. CNIO Publication. Open Access
Kataru RP, Baik JE, Park HJ, Ly CL, Shin J, Schwartz N, Lu TT, Ortega S, Mehrara BJ. (2021). Lymphatic-specific intracellular modulation of receptor tyrosine kinase signaling improves lymphatic growth and function. Sci Signal 14, eabc0836. CNIO Publication.
González-Martínez J, Cwetsch AW, Martínez-Alonso D, López-Sainz LR, Almagro J, Melati A, Gómez J, Pérez-Martínez M, Megías D, Boskovic J, Gilabert-Juan J, Graña-Castro O, Pierani A, Behrens A, Ortega S, Malumbres M. (2021). Deficient adaptation to centrosome duplication defects in neural progenitors causes microcephaly and subcortical heterotopias. JCI Insight 6, 146364. CNIO Publication.
Lynch CJ, Bernad R, Martínez-Val A, Shahbazi MN, Nóbrega-Pereira S, Calvo I, Blanco-Aparicio C, Tarantino C, Garreta E, Richart-Ginés L, Alcazar N, Graña-Castro O, Gómez-Lopez G, Aksoy I, Muñoz-Martín M, Martinez S, Ortega S, Prieto S, Simboeck E, Camasses A, Stephan-Otto Attolini C, Fernandez AF, Sierra MI, Fraga MF, Pastor J, Fisher D, Montserrat N, Savatier P, Muñoz J, Zernicka-Goetz M, Serrano M (2020). Global hyperactivation of enhancers stabilizes human and mouse naive pluripotency through inhibition of CDK8/19 Mediator kinases. Nat Cell Biol 22, 1223-1238. CNIO Publication.
Lioux G, Liu X, Temiño S, Oxendine M, Ayala E, Ortega S, Kelly RG, Oliver G, Torres M (2020). A second heart field-derived vasculogenic niche contributes to cardiac lymphatics. Dev Cell 52, 350-363. CNIO Publication.
Kalisz M, Bernardo E, Beucher A, Maestro MA, Del Pozo N, Millán I, Haeberle L, Schlensog M, Safi SA, Knoefel WT, Grau V, de Vas M, Shpargel KB, Vaquero E, Magnuson T, Ortega S, Esposito I, Real FX, Ferrer J (2020). HNF1A recruits KDM6A to activate differentiated acinar cell programs that suppress pancreatic cancer.. EMBO J 39, e102808. CNIO Publication.
Salazar-Roa M, Trakala M, Álvarez-Fernández M, Valdés-Mora F, Zhong C, Muñoz J, Yu Y, Peters TJ, Graña-Castro O, Serrano R, Zapatero-Solana E, Abad M, Bueno MJ, de Cedrón MG, Fernández-Piqueras J, Serrano M, Blasco MA, Wang DZ, Clark SJ, Izpisua-Belmonte JC, Ortega S, Malumbres M (2020). Transient Exposure to miR-203 Enhances the Differentiation Capacity of Established Pluripotent Stem Cells. EMBO J 39, e104324. CNIO Publication.
Blasco MT, Navas C, Martín-Serrano G, Graña-Castro O, Lechuga CG, Martín-Díaz L, Djurec M, Li Jing, Morales-Cacho L, Esteban-Burgos L, Perales-Patón J, Bousquet-Mur E, Castellano E, Jacob Harrys KC, Cabras L, Mustenau M, Drosten M, Ortega S, Mulero F, Sainz B, Dusetti N, Iovanna J, Sánchez-Bueno F, Hidalgo M, Khiabanian H, Hidalgo M, Rabadán R, Al-Shahrour F, Guerra C, Barbacid M (2019). Complete Regression of Advanced Pancreatic Ductal Adenocarcinomas upon Combined Inhibition of EGFR and C-RAF. Cancer Cell 35, 573-587. CNIO Publication.
Kataru RP, Ly CL, Shin J, Park HJ, Baik JE, Rehal S, Ortega S, Lyden D, Mehrara BJ (2019). Tumor Lymphatic Function Regulates Tumor Inflammatory and Immunosuppressive Microenvironments. Cancer Immunol Res 7, 1345-1358. CNIO Publication.
Olbrich T, Vega-Sendino M, Murga M, de Carcer G, Malumbres M, Ortega S, Ruiz S, Fernandez-Capetillo O (2019). A Chemical Screen Identifies Compounds Capable of Selecting for Haploidy in Mammalian Cells.. Cell Reports 28, 597-604. CNIO Publication. Open Access
Villahoz S, Yunes-Leites PS, Méndez-Barbero N, Urso K, Bonzon-Kulichenko E, Ortega S, Nistal JF, Vazquez J, Offermanns S, Redondo JM, Campanero MR (2018). Conditional deletion of Rcan1 predisposes to hypertension-mediated intramural hematoma and subsequent aneurysm and aortic rupture. Nat Commun 9, 4795. CNIO Publication. Open Access
Mayor-Ruiz C, Olbrich T, Drosten M, Lecona E, Vega-Sendino M, Ortega S, Dominguez O, Barbacid M, Ruiz S, Fernandez-Capetillo O (2018). ERF deletion rescues RAS deficiency in mouse embryonic stem cells. Genes Dev 32, 568-576. CNIO Publication. Open Access
Lynch CJ, Bernad R, Calvo I, Nóbrega-Pereira S, Ruiz S, Ibarz N, Martinez-Val A, Graña-Castro O, Gómez-López G, Andrés-León E, Espinosa Angarica V, Del Sol A, Ortega S, Fernandez-Capetillo O, Rojo E, Munoz J, Serrano M (2018). The RNA Polymerase II Factor RPAP1 Is Critical for Mediator-Driven Transcription and Cell Identity. Cell Reports 22, 396-410. CNIO Publication. Open Access
Vilas JM, Carneiro C, Da Silva-Álvarez S, Ferreirós A, González P, Gómez M, Ortega S, Serrano M, García-Caballero T, González-Barcia M, Vidal A, Collado M (2018). Adult Sox2+ stem cell exhaustion in mice results in cellular senescence and premature aging. Aging Cell 17, e12834. CNIO Publication. Open Access
Olmeda D, Cerezo-Wallis D, Riveiro-Falkenbach E, Pennacchi PC, Contreras-Alcalde M, Ibarz N, Cifdaloz M, Catena X, Calvo TG, Cañón E, Alonso-Curbelo D, Suarez J, Osterloh L, Graña O, Mulero F, Megías D, Cañamero M, Martínez-Torrecuadrada JL, Mondal C, Di Martino J, Lora D, Martinez-Corral I, Bravo-Cordero JJ, Muñoz J, Puig S, Ortiz-Romero P, Rodriguez-Peralto JL, Ortega S, Soengas MS (2017). Whole-body imaging of lymphovascular niches identifies pre-metastatic roles of midkine. Nature 546, 676-680. CNIO Publication.
Olbrich T, Mayor-Ruiz C, Vega-Sendino M, Gomez C, Ortega S, Ruiz S, Fernandez-Capetillo O (2017). A p53-dependent response limits the viability of mammalian haploid cells. Proc Natl Acad Sci USA 114, 9367-9372. CNIO Publication.
Muñoz S, Búa S, Rodríguez-Acebes S, Megías D, Ortega S, de Martino A, Méndez J (2017). In Vivo DNA Re-replication Elicits Lethal Tissue Dysplasias. Cell Reports 19, 928-938. CNIO Publication.
Chirivella L, Kirstein M, Ferrón SR, Domingo-Muelas A, Durupt FC, Acosta-Umanzor C, Cano-Jaimez M, Pérez-Sánchez F, Barbacid M, Ortega S, Burks D, Fariñas I (2017). Cdk4 regulates adult neural stem cell proliferation and differentiation in response to insulin-IRS2 signals. Stem Cells 35, 2403-2416. CNIO Publication.