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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:

 

Moran S, Martínez-Cardús A, Sayols S, Musulén E, Balana C, Estival-Gonzalez A, Moutinho C, Heyn H, Diaz-Lagares A, Castro de Moura M, Stella GM, Comoglio PM, Ruiz-Miró M, Matias-Guiu X, Pazo-Cid R, Antón A, Lopez-Lopez R, Soler G, Longo F, Guerra I, Fernandez S, Assenov Y, Plass C, Morales R, Carles J, Bowtell D, Mileshkin L, Sia D, Tothill R, Tabernero J, Llovet JM, Esteller M. Epigenetic profiling to classify cancer of unknown primary: a multicentre, retrospective analysis. The Lancet Oncology, 17, 1386–1395, 2016. 

 

Vizoso M, Ferreira HJ, Lopez-Serra P, Carmona FJ, Martínez-Cardús A, Girotti MR, Villanueva A, Guil S, Moutinho C, Liz J, Portela A, Heyn H, Moran S, Vidal A, Martinez-Iniesta M, Manzano JL, Fernandez-Figueras MT, Elez E, Muñoz-Couselo E, Botella-Estrada R, Berrocal A, Pontén F, Oord JV, Gallagher WM, Frederick DT, Flaherty KT, McDermott U, Lorigan P, Marais R, Esteller M. Epigenetic activation of a cryptic TBC1D16 transcript enhances melanoma progression by targeting EGFR. Nature Medicine, 21, 741-50, 2015.

 

Simo-Riudalbas L, Perez-Salvia M, Setien F, Villanueva A, Moutinho C, Martinez-Cardus A, Moran S, Berdasco M, Gomez A, Vidal E, Soler M, Heyn H, Vaquero A, de la Torre C, Barcelo-Batllori S, Vidal A, Roz L, Pastorino U, Szakszon K, Borck G, Moura C, Carneiro F, Zondervan I, Savola S, Iwakawa R, Kohno T, Yokota J, Esteller M. KAT6B is a tumor suppressor histone H3 lysine 23 acetyltransferase undergoing genomic loss in small cell lung cancer. Cancer Research, 75, 3936-45, 2015.

 

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, 55, 138-47, 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, 5, 3608, 2014.

 

Moutinho C, Martinez-Cardús A, Santos C, Navarro-Pérez V,  Martínez-Balibrea E, Musulen E, Carmona FJ, Sartore-Bianchi A, Cassingena A, Siena S, Elez E, Tabernero J, Salazar R, Abad A, Esteller M. Epigenetic Inactivation of the BRCA1 Interactor SRBC and Resistance to Oxaliplatin in Colorectal Cancer. The Journal of the National Cancer Institute, 106, doi: 10.1093/jnci/djt322, 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, 7, 331-8.

 

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.

 

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, 22, 407-19.

 

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.

 

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.

El proyecto con expediente: PIE13/00022 y título “A pilot project for personalized cancer medicine: oncoprofile “.Convocatoria de Proyectos Integrados de Excelencia de los institutos de investigación sanitaria, con un presupuesto de 770.000,00 € cofinanciado por el Fondo de Desarrollo Regional (FEDER) de la Unión Europea y el Instituto de Salud Carlos III. El Dr. Manel Esteller Badosa como IP Coordinador.

 

imatge personal
 

Group leader

Manel Esteller
Telephone  
+34 932607140
E-mail  
mesteller@idibell.cat
 
© 2016 Institut d'Investigació Biomèdica de Bellvitge



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