Research Area
Our main research interest is to decipher the role of chromosomal rearrangements in cancer initiation and progression to provide avenues for creating diagnostic and therapeutic tools by the use of genome editing by CRISPR.
Team Description
The research activity of the Molecular Cytogenetics and Genome Editing Unit focuses on increasing the knowledge about the role of chromosomal rearrangements in cancer development and progression and the discovery of new therapeutic targets. With the combined use of CRISPR genome editing and cytogenetic technologies, we are creating in vitro models that recapitulate chromosomal, genetic, and epigenetic cancer alterations. The goal of the Unit is to develop and implement the latest technologies used in the fields of molecular cytogenetics and genome engineering. We also participate in collaborative projects with clinical and basic science investigators at the CNIO and other institutions.
Team Members
Team Show
Publications
• Martinez-Lage M, Torres-Ruiz R, Puig-Serra P, Moreno-Gaona P, Martin MC, Moya FJ, Quintana-Bustamante O, Garcia-Silva S, Carcaboso AM, Petazzi P, Bueno C, Mora J, Peinado H, Segovia JC, Menendez P, Rodriguez-Perales S (2020). In vivo CRISPR/Cas9 targeting of fusion oncogenes for selective elimination of cancer cells. Nat Commun 11(1), 5060.
• Petazzi P, Torres-Ruiz R, Fidanza A, Roca-Ho H, Gutierrez-Agüera F, Castaño J, Rodriguez-Perales S, Díaz de la Guardia R, López-Millán B, Bigas A, Forrester LM, Bueno C, Menéndez P (2020). Robustness of Catalytically Dead Cas9 Activators in Human Pluripotent and Mesenchymal Stem Cells.. Molecular Therapy-Nucleic Acids 20, 196-204.
• Redondo-Antón J, Fontela MG, Notario L, Torres-Ruiz R, Rodríguez-Perales S, Lorente E, Lauzurica P (2020). Functional Characterization of a Dual Enhancer/Promoter Regulatory Element Leading Human CD69 Expression. Front Genet 11, 552949.
• Torres-Gomez A, Sanchez-Trincado JL, Toribio V, Torres-Ruiz R, Rodríguez-Perales S, Yáñez-Mó M, Reche PA, Cabañas C, Lafuente EM (2020). RIAM-VASP Module Relays Integrin Complement Receptors in Outside-In Signaling Driving Particle Engulfment. Cells 9(5), 1166.
• Molina O, Vinyoles M, Granada I, Roca-Ho H, Gutierrez-Agüera F, Valledor L, López-López CM, Rodríguez-González P, Trincado JL, Tirados-Menéndez S, Pal D, Ballerini P, Den Boer ML, Plensa I, Perez-Iribarne MDM, Rodriguez-Perales S, Calasanz MJ, Ramírez M, Rodríguez R, Camos M, Calvo M, Bueno C, Menendez P (2020). Impaired Condensin Complex and Aurora B kinase underlie mitotic and chromosomal defects in hyperdiploid B-cell ALL.. Blood 136, 313-327.
• Pino-Barrio MJ, Giménez Y, Villanueva M, Hildenbeutel M, Sánchez-Dominguez R, Rodríguez-Perales S, Pujol R, Surrallés J, Río P, Cathomen T, Mussolino C, Bueren JA, Navarro S (2020). TALEN mediated gene editing in a mouse model of Fanconi anemia.. Sci Rep 10, 6997.
• Visnes T, Benítez-Buelga C, Cázares-Körner A, Sanjiv K, Hanna BMF, Mortusewicz O, Rajagopal V, Albers JJ, Hagey DW, Bekkhus T, Eshtad S, Baquero JM, Masuyer G, Wallner O, Müller S, Pham T, Göktürk C, Rasti A, Suman S, Torres-Ruiz R, Sarno A, Wiita E, Homan EJ, Karsten S, Marimuthu K, Michel M, Koolmeister T, Scobie M, Loseva O, Almlöf I, Unterlass JE, Pettke A, Boström J, Pandey M, Gad H, Herr P, Jemth AS, El Andaloussi S, Kalderén C, Rodriguez-Perales S, Benítez J, Krokan HE, Altun M, Stenmark P, Berglund UW, Helleday T (2020). Targeting OGG1 arrests cancer cell proliferation by inducing replication stress.. Nucleic Acids Res 48, 12234-12251.
• Román-Rodríguez FJ, Ugalde L, Álvarez L, Díez B, Ramírez MJ, Risueño C, Cortón M, Bogliolo M, Bernal S, March F, Ayuso C, Hanenberg H, Sevilla J, Rodríguez-Perales S, Torres-Ruiz R, Surrallés J, Bueren JA, Río P (2019). NHEJ-Mediated Repair of CRISPR-Cas9-Induced DNA Breaks Efficiently Corrects Mutations in HSPCs from Patients with Fanconi Anemia. Cell Stem Cell 25, 607-621.
• Xu-Monette ZY, Xiao M, Au Q, Padmanabhan R, Xu B, Hoe N, Rodríguez-Perales S, Torres-Ruiz R, Manyam GC, Visco C, Miao Y, Tan X, Zhang H, Tzankov A, Wang J, Dybkær K, Tam W, You H, Bhagat G, Hsi ED, Ponzoni M, Ferreri AJM, Møller MB, Piris MA, van Krieken JH, Winter JN, Westin JR, Pham LV, Medeiros LJ, Rassidakis GZ, Li Y, Freeman GJ, Young KH (2019). Immune Profiling and Quantitative Analysis Decipher the Clinical Role of Immune-Checkpoint Expression in the Tumor Immune Microenvironment of DLBCL. Cancer Immunol Res 7, 644-657.
• Escudero-Paniagua B, Bartolomé RA, Rodríguez S, de Los Ríos V, Pintado L, Jaen M, Lafarga M, Fernández-Aceñero MJ, Casal J (2019). PAUF/ZG16B promotes colorectal cancer progression through alterations of the mitotic functions and the Wnt/ß-catenin pathway. Carcinogenesis 41(2), 203-213.
• Torres-Ruiz R, Benítez-Burraco A, Martínez-Lage M, Rodríguez-Perales S, García-Bellido P (2019). Functional characterization of two enhancers located downstream FOXP2. BMC Med Genet. 20, 65.
• Bonafont J, Mencía Á, García M, Torres R, Rodríguez S, Carretero M, Chacón-Solano E, Modamio-Høybjør S, Marinas L, León C, Escamez MJ, Hausser I, Del Río M, Murillas R, Larcher F (2019). Clinically Relevant Correction of Recessive Dystrophic Epidermolysis Bullosa by Dual sgRNA CRISPR/Cas9-Mediated Gene Editing. Mol Ther 27, 986-998.
• Brandt M, Grazioso TP, Fawal MA, Tummala KS, Torres-Ruiz R, Rodriguez-Perales S, Perna C, Djouder N (2018). mTORC1 inactivation promotes colitis-induced colorectal cancer. Cell Metab 27, 118-135.
• Oldrini B, Curiel-García Á, Marques C, Matia V, Uluçkan Ö, Graña-Castro O, Torres-Ruiz R, Rodriguez-Perales S, Huse JT, Squatrito M (2018). Somatic genome editing with the RCAS-TVA-CRISPR-Cas9 system for precision tumor modeling. Nat Commun 9, 1466.
• Sánchez-Hernández S, Gutierrez-Guerrero A, Martín-Guerra R, Cortijo-Gutierrez M, Tristán-Manzano M, Rodriguez-Perales S, Sanchez L, Garcia-Perez JL, Chato-Astrain J, Fernandez-Valades R, Carrillo-Galvez AB, Anderson P, Montes R, Real PJ, Martin F, Benabdellah K (2018). The IS2 Element Improves Transcription Efficiency of Integration-Deficient Lentiviral Vector Episomes. Molecular Therapy-Nucleic Acids 13, 16-28.
• Martinez-Lage M, Puig-Serra P, Menendez P, Torres-Ruiz R, Rodriguez-Perales S (2018). CRISPR/Cas9 for Cancer Therapy: Hopes and Challenges. Biomedicines 6, E105.
• Mur P, De Voer RM, Olivera-Salguero R, Rodríguez-Perales S, Pons T, Setién F, Aiza G, Valdés-Mas R, Bertini A, Pineda M, Vreede L, Navarro M, Iglesias S, González S, Brunet J, Valencia A, Esteller M, Lázaro C, Kops GJPL, Urioste M, Puente XS, Capellá G, Valle L (2018). Germline mutations in the spindle assembly checkpoint genes BUB1 and BUB3 are infrequent in familial colorectal cancer and polyposis. Mol Can 17, 23.
• Benítez-Burraco A, Barcos-Martínez M, Espejo-Portero I, Fernández-Urquiza M, Torres-Ruiz R, Rodríguez-Perales S, Jiménez-Romero MS (2018). Narrowing the genetic causes of language dysfunction in the 1q21.1 microduplication syndrome. Front Pediatr 6, 163.
• Remacha L, Currás-Freixes M, Torres-Ruiz R, Schiavi F, Torres-Pérez R, Calsina B, Letón R, Comino-Méndez I, Roldán-Romero JM, Montero-Conde C, Santos M, Pérez LI, Pita G, Alonso MR, Honrado E, Pedrinaci S, Crespo-Facorro B, Percesepe A, Falcioni M, Rodríguez-Perales S, Korpershoek E, Ramón-Maiques S, Opocher G, Rodríguez-Antona C, Robledo M, Cascón A (2018). Gain-of-function mutations in DNMT3A in patients with paraganglioma. Genet Med 20, 1644-1651.
• Torres-Ruiz R, Rodriguez-Perales S, Bueno C, Menendez P (2017). Modeling mixed-lineage-rearranged leukemia initiation in CD34+ cells: a “CRISPR” solution. Haematologica 102, 1467-168.
• Diez B, Genovese P, Roman-Rodriguez FJ, Alvarez L, Schiroli G, Ugalde L, Rodriguez-Perales S, Sevilla J, Diaz de Heredia C, Holmes MC, Lombardo A, Naldini L, Bueren JA, Rio P (2017). Therapeutic gene editing in CD34+ hematopoietic progenitors from Fanconi anemia patients. EMBO Mol Med 9, 1574-1588.
• Torres-Ruiz R, Martinez-Lage M, Martin MC, Garcia A, Bueno C, Castaño J, Ramirez JC, Menendez P, Cigudosa JC, Rodriguez-Perales S (2017). Efficient Recreation of t(11;22) EWSR1-FLI1+ in Human Stem Cells Using CRISPR/Cas9. Stem Cell Reports 8, 1408-1420.
• Castaño J, Bueno C, Jiménez-Delgado S, Roca-Ho H, Fraga MF, Fernandez AF, Nakanishi M, Torres-Ruiz R, Rodríguez-Perales S, Menéndez P (2017). Generation and characterization of a human iPSC cell line expressing inducible Cas9 in the “safe harbor” AAVS1 locus. Stem Cell Res 21, 137-140.
• Torres-Ruiz R, Rodriguez-Perales S (2017). CRISPR-Cas9 technology: applications and human disease modelling.. Brief Funct Genomics 16, 4-12.
• Martinez-Lage M, Torres-Ruiz R, Rodriguez-Perales S (2017). CRISPR/Cas9 Technology: Applications and Human Disease Modeling.. Prog Mol Biol Transl Sci 152, 23-48.
• Rodriguez-Perales S, Torres-Ruiz R, Suela J, Acquadro F, Martin MC, Yebra E, Ramirez JC, Alvarez S, Cigudosa JC (2016). Truncated RUNX1 protein generated by a novel t(1;21)(p32;q22) chromosomal translocation impairs the proliferation and differentiation of human hematopoietic progenitors.. Oncogene 35, 125-134.
• Muñoz-López A, Romero-Moya D, Prieto C, Ramos-Mejía V, Agraz-Doblas A, Varela I, Buschbeck M, Palau A, Carvajal-Vergara X, Giorgetti A, Ford A, Lako M, Granada I, Ruiz-Xivillé N, Rodríguez-Perales S, Torres-Ruíz R, Stam RW, Fuster JL, Fraga MF, Nakanishi M, Cazzaniga G, Bardini M, Cobo I, Bayon GF, Fernandez AF, Bueno C, Menendez P (2016). Development refractoriness of MLL-rearranged human B cell acute leukemias to reprogramming into pluripotency. Stem Cell Reports 7, 602-618.
• Torres R, Martin MC, Garcia A, Cigudosa JC,Ramirez JC, Rodriguez-Perales S (2014). Engineering human tumour-associated chromosomal translocations with the RNA-guided CRISPR-Cas9 system. Nat Commun 3;5, 3964.