Elena Klenova

CTCF and BORIS in normal development, epigenetics and

tumourigenesis

Areas of research:

• Molecular Oncology• Gene regulation•Translational research : clinical links via EBSI

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

CTCF and its known modifications and interacting

partners

Ohlsson et al, 2010

 

CTCF plays an important role in the regulation of nuclear

architecture:Genome-wide CTCF-mediated

chromatin interactome

Handoko et al., 2011

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.

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

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.

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