Unidad de Edición Genómica en Ratón

Sagrario Ortega Jefe de Unidad
T +34 917328000 (Ext 3170)
sortega@cnio.es

Técnicos de Laboratorio

Beatriz Escobar
Carmen Gómez
Melani Margullón
Jaime Muñoz
Patricia Prieto
Pierfrancesco Vargiu

Cancer encompasses an extensive range of highly intricate diseases. Alterations in the genetic and epigenetic makeup of tumour cells result in the acquisition of «malignant» characteristics, allowing them to elude normal physiological regulation. Techniques involving genome editing and transgenesis are employed to faithfully replicate these changes in mice, creating indispensable animal models essential for comprehending and improving cancer treatment. Tumour cells engage with various bodily systems, including the immune, cardiovascular, and lymphatic systems, influencing tumour growth, invasion, and expansion. Behavioural elements such as diet or smoking also influence cancer development. To unravel this intricate complexity, dependable in vivo models are imperative, replicating cancer features in a comprehensive «whole body» setting. The precise, targeted, and controlled manipulation of the mouse genome, utilising cutting-edge genome editing tools, facilitates the development of genetic mouse models crucial for deciphering the molecular mechanisms of tumour formation and for preclinically validating advanced and more effective cancer therapies.

Publicaciones

Sanz-Flores M, Ruiz-Torres M, Aguirre-Portolés C, El Bakkali A, Salvador-Barberó B, Villarroya-Beltri C, Ortega S, Megías D, Gerlich DW, Álvarez-Fernández M, Malumbres M. (2024). PP2A-B55 phosphatase counteracts Ki-67-dependent chromosome individualization during mitosis. Cell Reports 43, 114494. Publicación CNIO.
de la Rosa S, Del Mar Rigual M, Vargiu P, Ortega S, Djouder N. (2024). Endogenous retroviruses shape pluripotency specification in mouse embryos. Sci Adv 10, eadk9394. Publicación CNIO.
González-Martínez J, Sánchez-Belmonte A, Ayala E, García A, Nogueira E, Muñoz J, Melati A, Giménez D, Losada A, Ortega S, Malumbres M (2024). miR-203 controls developmental timing and early fate restriction during preimplantation embryogenesis.. BioRxiv (in press). Publicación CNIO.
Sayago C, Sánchez-Wandelmer J, García F, Hurtado B, Lafarga V, Prieto P, Zarzuela E, Ximénez-Embún P, Ortega S, Megías D, Fernández-Capetillo O, Malumbres M, Munoz J. (2023). Decoding protein methylation function with thermal stability analysis.. Nat Commun 14, 3016. Publicación CNIO.
Maus M, López-Polo V, Mateo L, Lafarga M, Aguilera M, De Lama E, Meyer K, Sola A, Lopez-Martinez C, López-Alonso I, Guasch-Piqueras M, Hernandez-Gonzalez F, Chaib S, Rovira M, Sanchez M, Faner R, Agusti A, Diéguez-Hurtado R, Ortega S, Manonelles A, Engelhardt S, Monteiro F, Stephan-Otto Attolini C, Prats N, Albaiceta G, Cruzado JM, Serrano M. (2023). Iron accumulation drives fibrosis, senescence and the senescence-associated secretory phenotype. Nat Metabolism 5, 2111-2130. Publicación CNIO. Open Access
Beucher A, Miguel-Escalada I, Balboa D, De Vas MG, Maestro MA, Garcia-Hurtado J, Bernal A, Gonzalez-Franco R, Vargiu P, Heyn H, Ravassard P, Ortega S, Ferrer J (2022). The HASTER lncRNA promoter is a cis-acting transcriptional stabilizer of HNF1A. Nat Cell Biol 24, 1528-1540. Publicación CNIO. Open Access
Fernández LP, Deleyto-Seldas N, Colmenarejo G, Sanz A, Wagner S, Plata-Gómez AB, Gómez-Patiño M, Molina S, Espinosa-Salinas I, Aguilar-Aguilar E, Ortega S, Graña-Castro O, Loria-Kohen V, Fernández-Marcos PJ, Efeyan A, Ramírez de Molina A. (2022). Folliculin-interacting protein FNIP2 impacts on overweight and obesity through a polymorphism in a conserved 3′ untranslated region. Genome Biol 23, 230. Publicación CNIO. Open Access
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. Publicación CNIO.
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. Publicación CNIO. 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. Publicación CNIO. 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. Publicación CNIO.
García-Silva S, Benito-Martín A, Nogués L, Hernández-Barranco A, Mazariegos MS, Santos V, Hergueta-Redondo M, Ximénez-Embún P, Kataru RP, Lopez AA, Merino C, Sánchez-Redondo S, Graña-Castro O, Matei I, Nicolás-Avila JÁ, Torres-Ruiz R, Rodríguez-Perales S, Martínez L, Pérez-Martínez M, Mata G, Szumera-Cieckiewicz A, Kalinowska I, Saltari A, Martínez-Gómez JM, Hogan SA, Saragovi HU, Ortega S, Garcia-Martin C, Boskovic J, Levesque MP, Rutkowski P, Hidalgo A, Muñoz J, Megías D, Mehrara BJ, Lyden D, Peinado H (2021). Melanoma-derived small extracellular vesicles induce lymphangiogenesis and metastasis through an NGFR-dependent mechanism. Nat Cancer 2, 1387-1405. Publicación CNIO.
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. Publicación CNIO.
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. Publicación CNIO.
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. Publicación CNIO.
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. Publicación CNIO. Open Access
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. Publicación CNIO. Open Access
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. Publicación CNIO.
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. Publicación CNIO.
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. Publicación CNIO. Open Access