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Cancer Epigenetics

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Research lines

. Definition of the Epigenome of Cancer Cells: Profile of DNA methylation and histone modifications in tumor suppressor genes and repetitive sequences in cancer. Global and gene-specific definition of aberrant epigenetic changes and functional consequences in transcription regulation, DNA repair and chromosome instability.

. Study of the Epigenetics Machinery and Mechanisms: Role and function of DNA methyltransferases (enzymes that maintain DNA methylation), specificity of methyl-CpG binding domain proteins (the nuclear factors that recognize DNA methylation), analysis of biological properties of histone deacetylases and methyltransferases (enzymes that modify histones).

. Study of Mutations in the Epigenetic Machinery: The mechanisms underlying the disruption of the epigenetic landscape in transformed cells are unknown. It is possible that the enzymes that epigenetically modify DNA and histone are themselves targets of genetic disruption. Mutational analysis of “epigenetic modifier genes”.

. Testing of Epigenetic Drugs: Study of the biological effects in cell lines and mouse models of different small epigenetic drugs directed against DNA methylatransferases, histone deacetylases and other enzymes of the epigenetic machinery. Analysis of their use as anticancer drugs.


Selected Publications:

 

Liz J, Portela A, Soler M, Gómez A, Ling H, Michlewski G, Calin GA, Guil S, Esteller M. RNA-Directed Regulation of pri-miRNA Processing by a Long Noncoding RNA Transcribed from an Ultraconserved Region. Molecular Cell, doi: 10.1016/j.molcel.2014.05.005, 2014

 

Lopez-Serra P, Marcilla M, Villanueva A, Ramos-Fernandez A, Palau A, Leal L, Wahi JE, Setien-Baranda F, Szczesna K, Moutinho C, Martinez-Cardus A, Heyn H, Sandoval J, Puertas S, Vidal A, Sanjuan X, Martinez-Balibrea E, Viñals F, Perales JC, Bramsem JB, Ørntoft TF, Andersen CL, Tabernero J, McDermott U, Boxer MB, Vander Heiden MG, Albar JP,  Esteller M. A DERL3 Associated Defect in the Degradation of SLC2A1 Mediates the Warburg Effect. Nature Communications, April 3, 5:3608. doi: 10.1038/ncomms4608, 2014.

 

Heyn H, Sayols S, Moutinho C, Vidal E, Sanchez-Mut JV, Stefansson OA, Nadal E, Moran S, Eyfjord J, Gonzalez-Suarez E, Pujana MA, Esteller M. Linkage of DNA Methylation Quantitative Trait Loci to Human Cancer Risk. Cell Reports, April 2, doi: 10.1016/j.celrep.2014.03.016, 2014.

 

Heyn H, Moran S, Hernando-Herraez I, Sayols S, Gomez A, Sandoval J, Monk D, Hata K, Marques-Bonet T, Wang L, Esteller M. DNA methylation contributes to natural human variation. Genome Research, 23, 1363-72, 2013.

 

Lister R, Mukamel EA, Nery JR, Urich M, Puddifoot CA, Johnson ND, Lucero J, Huang Y, Dwork AJ, Schultz MD, Yu M, Tonti-Filippini J, Heyn H, Hu S, Wu JC, Rao A, Esteller M, He C, Haghighi FG, Sejnowski TJ, Behrens MM, Ecker JR. Global Epigenomic Reconfiguration During Mammalian Brain Development. Science, 341, 1237905, 2013.

 

Heyn H, Li N, Ferreira HJ, Moran S, Pisano DG, Gomez A, Diez J, Sanchez-Mut JV, Setien F, Carmona FJ, Pucaf AA Sayols S, Pujana MA, Serra-Musach J, Iglesias-Plata I, Formiga F, Fernandez AF, Fraga MF, Heath S, Valencia A, Gut IG, Wang J, Esteller M. The Distinct DNA Methylomes of Newborns and Centenarians. Proc Natl Acad Sci USA, 109, 10522-7, 2012.

 

Guil S, Soler M, Portela A, Carrère J, Fonalleras E, Gómez A, Villanueva A, Esteller M. Intronic RNAs mediate EZH2 regulation of epigenetic targets. Nature Structural & Molecular Biology, 19, 664-70, 2012.

 

Melo S, Villanueva A, Moutinho C, Davalos V, Spizzo R, Ivan C, Rossi S, Setien F, Casanovas O, Sio-Riudalbas L, Carmona FJ, Carrere J, Vidal A, Aytes A, Puertas S, Ropero S, Kalluri R, Croce CM, Calin GA, Esteller M. The small molecule enoxacin is a cancer-specific growth inhibitor that acts by enhancing TAR RNA-binding protein 2-mediated microRNA processing. Proc Natl Acad Sci USA, 108, 4394-9, 2011.

 

Fernandez AF, Assenov Y, Martin-Subero JI, Balint B, Siebert R, Taniguchi H, Yamamoto H, Hidalgo M, Tan AC, Galm O, Ferrer I, Sanchez-Cespedes M, Villanueva A, Carmona FJ, Sanchez-Mut JV, Berdasco M, Moreno V, Capella G, Monk D, Ballestar E, Ropero S, Martinez R, Sanchez-Carbayo M, Prosper F, Agirre X, Fraga MF, Graña O, Perez-Jurado L, Mora J, Puig S, Prat J, Badimon L, Puca AA, Meltzer SJ, Lengauer T, Bridgewater J, Bock C, Esteller M. A DNA Methylation Fingerprint of 1,628 Human Samples. Genome Research, July 12, 2011.

 

Huertas D, Soler M, Moreto J, Villanueva A, Martinez A, Vidal A, Charlton M, Moffat D, Patel S, McDermott J, Owen J, Brotherton D, Krige D, Cuthill S, Esteller M. Antitumor Activity of a Small Molecule Inhibitor of the Histone Kinase Haspin. Oncogene, August 1, 2011

 

Melo SA, Moutinho C, Ropero S, Calin GA, Rossi S, Spizzo R, Fernandez AF, Davalos V, Villanueva A, Yamamoto H, Schwartz Jr, Esteller M. A Genetic Defect in Exportin-5 Traps Precursor MicroRNAs in the Nucleus of Cancer Cells. Cancer Cell, 18, 303–15, 2010.

 

Berdasco M, Ropero S, Setien F, Fraga MF, Lapunzina P, Lossone R, Alaminos M, Cheung NK, Rahmanh N, Esteller M. Epigenetic inactivation of the Sotos overgrowth syndrome gene histone methyltransferase NSD1 in human neuroblastoma and glioma. Proc Natl Acad Sci USA, 106, 21830-35, 2009.

 

Melo SA, Ropero S, Moutinho C, Aaltonen LA, Yamamoto H, Calin GA, Rossi S, Fernandez AF, Carneiro F, Oliveira C, Ferreira B, Liu CG, Villanueva A, Capella G, Schwartz Jr S, Shiekhattar R, Esteller M. A TARBP2 mutation in human cancer impairs microRNA processing and DICER1 function. Nature Genetics, 41, 365-70, 2009.

 

Fernandez AF, Rosales C, Lopez-Nieva P, Graña O, Ballestar E, Ropero S, Espada J, Melo SA, Lujambio A, Fraga MF, Pino I, Javierre B, Carmona FJ, Acquadro F, Steenbergen RDM, Snijders PJF, Chris J. Meijer, Pascal Pineau, Anne Dejean, Lloveras B, Capella G, Quer J, Buti M, Esteban JI, Allende H, Rodriguez-Frias F, Castellsague X, Minarovits J, Ponce J, Capello D, Gaidano G, Cigudosa JC, Gomez-Lopez G, Pisano DG, Valencia A, Piris MA, Bosch FX, Cahir-McFarland E, Kieff E, Esteller M. The dynamic DNA methylomes of double-stranded DNA viruses associated with human cancer. Genome Research, 323, 1600-4, 2009.

 

Lujambio A, Calin GA, Villanueva A, Ropero S, Sánchez-Céspedes M, Blanco D, Montuenga LM, Rossi S, Nicoloso MS, Faller WJ, Gallagher WM, Eccles SA, Croce CM, Esteller M. A microRNA DNA methylation signature for human cancer metastasis. Proc Natl Acad Sci USA, 105, 13556-61, 2008.

 

 

Esteller M. Epigenetics of cancer. New England Journal of Medicine, 358, 1148-59, 2008.

imatge personal
 

Group leader

Manel Esteller
Telephone  
+34 932607140
E-mail  
mesteller@idibell.cat
 
© 2014 Institut d'Investigació Biomèdica de Bellvitge



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