Cancer Epigenetics

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.