• Function of  CTCF and BORIS in the hematopoietic differentiation. We aim to explore the function of CTCF and BORIS in hematopoietic differentiation through the analysis of their target genes, using cell lines and primary cells. The  methodology includes DNA interaction analysis , epigenetic regulation assays, modulation expression, profiling analysis, etc.
• To know the CTCF and BORIS involvement in hematological malignancies, especially in lymphomas. We use lymphoma cell lines and  samples from patients. We will also analyze the expression of these regulators in different subtypes of myelodisplatic syndromes and acute myeloid leukemia. The aim is to determine if CTCF and/or BORIS could be markers for diagnosis or prognosis in hematological neoplasias.

Funding:

• Función de los reguladores transcripcionales CTCF y CTCF-L (BORIS) en la diferenciación hematopoyética normal y patológica. Instituto de Salud Carlos III. FIS11/00397
• Terapia epigenética en linfomas de células B. Papel de los reguladores de cromatina de la familia CTCF. Entidad financiadora: Celgene S.L.U.

Publications:

Batlle-López, A., Cortiguera, M;  Rosa-Garrido, Blanco, R. M.,del Cerro, E., Wagner, S.D. and Delgado, M.D. Novel CTCF binding at a site in exon 1A of BCL6 is associated with active histone marks and a transcriptionally active locus. ONCOGENE in press

Gómez-Casares MT, García-Alegria E, López-Jorge CE, Ferrándiz N, Blanco R,Alvarez S, Vaqué JP, Bretones G, Caraballo JM, Sánchez-Bailón P, Delgado MD,Martín-Perez J, Cigudosa JC, León J.  MYC antagonizes the differentiation induced byimatinib in chronic myeloid leukemia cells through downregulation ofp27(KIP1). ONCOGENE. 2013 Apr 25;32(17):2239-46

Delgado MD, Albajar M, Gomez-Casares MT, Batlle A, León J.  MYC oncogene in myeloid neoplasias. Clin Transl Oncol. 2013 Feb;15(2):87-94.

Grande L, Bretones G, Rosa-Garrido M, Garrido-Martin EM, Hernandez T, FraileS, Botella L, de Alava E, Vidal A, Garcia del Muro X, Villanueva A, Delgado MD,Fernandez-Luna JL. Transcription factors Sp1 and p73 control the expression ofthe proapoptotic protein NOXA in the response of testicular embryonal carcinomacells to cisplatin.  JOURNAL OF BIOLOGICAL CHEMISTRY. 2012 Aug 3;287(32):26495-505.. Epub 2012 Jun 20.

Rosa-Garrido M, Ceballos L, Alonso-Lecue P, Abraira C, Delgado MD, Gandarillas A.  A cell cycle role for the epigenetic factor CTCF-L/BORIS. PLoS One.2012;7(6):e39371.

Sleutels F, Soochit W, Bartkuhn M, Heath H, Dienstbach S, Bergmaier P, FrankeV, Rosa-Garrido M, van de Nobelen S, Caesar L, van der Reijden M, Bryne JC, vanIjcken W, Grootegoed JA, Delgado MD, Lenhard B, Renkawitz R, Grosveld F, Galjart N. The male germ cell gene regulator CTCFL is functionally different from CTCFand binds CTCF-like consensus sites in a nucleosome composition-dependent manner. EPIGENETICS & CHROMATIN 2012 Jun 18;5(1):8.

Ferrándiz N, Caraballo JM, García-Gutierrez L, Devgan V, Rodriguez-Paredes M, Lafita MC, Bretones G, Quintanilla A, Muñoz-Alonso MJ, Blanco R, Reyes JC, Agell N, Delgado MD, Dotto GP, León J.  p21 as a transcriptionalco-repressor of S-phaseand mitotic control genes. PLoS One. 2012;7(5):e37759.

Albajar, M., Gómez-Casares, M.T., Llorca, J., Mauleon, J., Vaqué, J.P., Acosta, J.C., Bermúdez, A., Donato, N., Delgado, M.D. and León, J.  MYC in chronic myeloid leukemia: induction of aberrant DNA synthesis and association with poor response to imatinib. MOLECULAR CANCER RESEARCH 2011. 9, 564-576

Agúndez,L., Machón,C.,  César, C.E., l Rosa-Garrido,M.,  Delgado, M.D., and Llosa, M.* Nuclear targeting of a bacterial integrase which mediates site-specific recombination between bacterial and human target sequences. APPLIED AND ENVIRONMENTAL MICROBIOLOGY 2011. 77, 201–210

Van de Nobelen, S., Rosa-Garrido, M., Leers, J., Heath, H., Soochit, W., Joosen, L., Jonkers, I., Demmers, J., Van der Reijden, M., Torrano, V., Grosveld, F., Delgado, M.D., Renkawitz, R., ,Galjart, N..and Sleutels, F. “CTCF regulates the local epigenetic state of ribosomal DNA repeats”. EPIGENETICS & CHROMATIN 2010, 3:19

Delgado, M.D and León, J. Myc roles in hematopoiesis and leukemia.GENES&CANCER 2010 1(6) 605–616. Review.

Ferrandiz, N, Caraballo, J. M., Albajar, M, Gomez-Casares, M.T., López-Jorge, C.E., Blanco, R., Delgado, M.D. and Leon, J p21Cip1 confers resistance to imatinib in human chronic myeloid leukemia cells".CANCER LETTERS 2010. 292, 133-139

León J*, Ferrándiz, N, Acosta, JC, Delgado, MD Inhibition of cell differentiation: a critical mechanism for MYC-mediated carcinogenesis?. CELL CYCLE 2009. 8, 1148-1157.

Ferrandiz, N., Martin-Perez, J., Blanco, R, Donertas, D, Weber, A, Eilers, M, Dotto, P, Delgado, M.D. and Leon, J.

HCT116 cells deficient in p21Waf1 are hypersensitive to tyrosine kinase inhibitors and adriamycin through a mechanism unrelated to p21 and dependent on p53. DNA REPAIR 2009; 8, 390-399.

Acosta, J. C., Ferrándiz, N., Bretones, G., Blanco.,R., Torrano, V., Richard,C., O’Conell, B., Sedivy, J., Delgado, M.D., León, J. Myc inhibits p27-induced erythroid differentiation of leukemia cells by repressing erythroid master genes without reversing the p27-mediated cell cycle arrest . MOLECULAR AND CELLULAR BIOLOGY 2008; 28, 7286-7295.

Albajar, M. Gutierrez, P.,  Richard, C., Rosa-Garrido, M., Gómez-Casares, M.T., Steegmann, J.L. León, J. and Delgado M. D. PU.1 expression is restored upon treatment of chronic myeloid leukemia patients. CANCER LETTERS, 2008; 270, 328-336.

Renaud S, Pugacheva EM, Delgado MD, Braunschweig R, Abdullaev Z, Loukinov D, Benhattar J, Lobanenkov V. Expression of the CTCF-paralogous cancer-testis gene, brother of the regulator of imprinted sites (BORIS), is regulated by three alternative promoters modulated by CpG methylation and by CTCF and p53 transcription factors. NUCLEIC ACIDS RESEARCH. 2007; 35:7372-7388.

Sancho P, Galeano E, Nieto E, Delgado MD, García-Pérez AI.Dequalinium induces cell death in human leukemia cells by early mitochondrial alterations which enhance ROS production. LEUKEMIA RESEARCH 2007 Jul;31(7):969-978. Epub 2007 Jan 23.

Delgado MD, León J.Gene expression regulation and cancer. CLINICAL & TRANSLATIONAL ONCOLOGY. 2006;8:780-787.

D'Arcy V, Abdullaev ZK, Pore N, Docquier F, Torrano V, Chernukhin I, Smart M, Farrar D, Metodiev M, Fernandez N, Richard C, Delgado MD, Lobanenkov V, Klenova E.The potential of BORIS detected in the leukocytes of breast cancer patients as an early marker of tumorigenesis. CLINICAL CANCER RESEARCH. 2006; 12 (20): 5978-5986

Torrano V, Navascués J, Docquier F, Zhang R, Burke LJ, Chernukhin I, Farrar D, León J, Berciano MT, Renkawitz R, Klenova E, Lafarga M, Delgado MD.Targeting of CTCF to the nucleolus inhibits nucleolar transcription through a poly(ADP-ribosyl)ation-dependent mechanism. Article selected for editorial comment: "CTCF shuttle puts brakes on growth" JOURNAL OF CELL SCIENCE 2006;119:1746-1759.

Torrano V, Chernukhin I, Docquier F, D'Arcy V, León J, Klenova E, Delgado MD. CTCF regulates growth and erythroid differentiation of human myeloid leukemia cells. JOURNAL OF BIOLOGICAL CHEMISTRY. 2005;280(30):28152-28161.

Galeano E, Nieto E, García-Pérez AI, Delgado MD, Pinilla M, Sancho P. Effects of the antitumoural dequalinium on NB4 and K562 human leukemia cell lines. Mitochondrial implication in cell death. LEUKEMIA RESEARCH 2005 29:1201-1211.

Muñoz-Alonso MJ, Acosta JC, Richard C, Delgado MD, Sedivy J, León J. p21Cip1 and p27Kip1 induce distinct cell cycle effects and differentiation programs in myeloid leukemia cells. JOURNAL OF BIOLOGICAL CHEMISTRY. 2005 ; 280:18120-18129.

Contact:

Dra. Dolores Delgado

Phone: (+34) 942 201998 / Fax : (+34) 942 266399

Email: delgadmd@unican.es

Mailing address: IBBTEC. C/ Albert Einstein 22, PCTCAN, 39011 Santander