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Elena Klenova
CTCF and BORIS in normal development, epigenetics and
tumourigenesis
Areas of research:
• Molecular Oncology• Gene regulation•Translational research : clinical links via EBSI
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CTCFCTCF and and BORISBORIS
CTCFCTCF, named for “CCTC binding factor” in , named for “CCTC binding factor” in 19901990
BORISBORIS, for “, for “BBrother of the rother of the RRegulator of egulator of IImprinted mprinted SSites” in 2002ites” in 2002
Transcription factors with common DNA – binding domain:
Normally expressedin testis
Ubiquitouslyexpressed
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CTCF and its known modifications and interacting
partners
Ohlsson et al, 2010
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CTCF plays an important role in the regulation of nuclear
architecture:Genome-wide CTCF-mediated
chromatin interactome
Handoko et al., 2011
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Theme 1. Role of CTCF and BORIS in normal development and
tumourigenesis. • Cellular functions regulated by BORIS and CTCF
( apoptosis, proliferation); role of post-translational modifications and protein partners.
• Individual genes regulated by CTCF and BORIS.• Genome-wide studies of gene expression and
CTCF/BORIS binding to DNA.• Mechanisms of BORIS abnormal activation and cancer.• Tumour immunology (interaction between tumours
and immune cells).• Structural analysis of CTCF/DNA complexes.• CTCF and BORIS in stem cells (potential).• CTCF and viral infection (potential).Collaborations:• Existing - Metodi, Nelson, Philippe, Igor• Potential – Greg, Ralf/Andrea, Glyn, Mike H.
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Models: • cell lines, primary cells and tumour tissue specimens.
Methods: • Manipulation with gene expression levels ( siRNA, ectopic expression, stable and inducible cell lines, lentiviruses ( in progress);• DNA manipulations (mutagenesis, methylation etc);• Imaging ( immunocytochemistry, immunohistochemistry, immunofluorescene staining);• Proteomics;• Genomics (RNA-Seq, ChIP-Seq, microarray);•Bioinformatics (data analysis and interpretation);•Biological tests: proliferation (MTT), apoptosis (TUNEL).
Theme 1. The role of CTCF and BORIS in tumourigenesis: models
and methods
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Theme 2. Novel cancer biomarkers and drug targets •Identification and characterization of novel
cancer biomarkers (tissue, blood and potentially urine) and drug targets (tissue).• Assessment of CTCF and BORIS as potential diagnostic and prognostic biomarkers in common cancers, such as breast and prostate tumours.
Collaborations:Existing: Metodi, Harry.Potential: Phil R, Chris R, Berthold.
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Theme 2. Novel cancer biomarkers and drug targets. Materials and methods Materials:
Blood, tissues; urine ( in progress)
Methods:• Proteomics ( 2xD gel electrophoresis, mass-spectrometry);• Genomics + bioinformatics ( mainly existing databases);•Statistics