PEBC Report - Programa de Epigenética y Biología del Cáncer

PEBC RESEARCH GROUPS WITH THEIR LEADER BIOGRAPHIES, SCIENTIFIC INTERESTS AND ILLUSTRATIVE PUBLICATIONS
Dr Manel Esteller is the Director of the
Cancer Epigenetics and Biology Program
of the Bellvitge Institute for Biomedical
Research (IDIBELL), Leader of the Cancer
Epigenetics Group, Professor of Genetics
in the School of Medicine of the University
of Barcelona, and an ICREA Research
Professor.
Associate Researchers
Agustin Fernandez, Dori Huertas,
Ramon Sendra, Sonia Guil,
Iñaki Martin-Subero
Postdoctoral researchers
Jurgen Veeck, Anna Portela,
Veronica Davalos, Maria Berdasco
PhD Students
Amaia Lujambo, Sonia Melo, Marta Kulis,
Javier Carmona, Jose Sanchez, Laia
Simo, Rocio Gonzalez
Technicians
Fernando Setien, Marta Soler, Miguel Lopez,
Catia Moutinho, Jordi Carrere
Research Interests
Our main interests are:
-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 (Esteller, N
Engl J Med, 2008; Ballestar and Esteller, Cell, 2008).
-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). An Illustrative example
is the regulation of DNMT3b by RNA binding proteins
(Lopez de Silanes et al., NAR, 2009).
-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”.
Proof-of principle was provided by HDAC2 (Ropero et
al., Nature Genetics, 2006).
- Testing of Epigenetic Drugs: Study of the biological
effects in cell lines and mouse models of different small
epigenetic drugs directed against DNA methyltransferases,
histone deacetylases and other enzymes of the
epigenetic machinery (Lara et al., Oncogene 2008;
Zubia et al., Oncogene 2009). Analysis of their use as
anticancer drugs.
Overview of research:
Cancer is an epigenetic disease characterized by the
breakdown of the DNA methylation and histone modification
patterns. The stability of our genome and correct
gene expression are maintained in large measure thanks
to a perfectly pre-established pattern of DNA methylation
and histone modifications. In cancer, this ideal scenario is
destroyed by the occurrence of an interesting phenomenon
whereby the regulatory regions (CpG islands) of certain
tumor suppressor genes become hypermethylated,
inactivating the gene as a consequence, whilst a wave of
hypomethylation occurs in the genome. We have developed
procedures (Chip-on-CHIP, MeDIP…) for massive
genomic screening to find new hypermethylated genes in
cancer cells and characterize their histone codes. Both
DNA methylation and histone modifications control the
activity of a third component of the epigenetic landscape,
non-coding RNAs, particularly microRNAs that are also
disrupted in human cancer.
Recent research achievements:
-Construction of epigenomic maps in health and disease:
An altered pattern of epigenetic modifications is
central to many common human diseases, including
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