Download Elena Klenova

Elena Klenova
CTCF and BORIS in normal
development, epigenetics and
tumourigenesis
Areas of research:
• Molecular Oncology
• Gene regulation
•Translational research : clinical
links via EBSI
CTCF and BORIS
Normally
Ubiquitously
expressed
expressed
in testis
Transcription factors with common DNA – binding domain:
CTCF, named for “CCTC binding factor” in 1990
BORIS, for “Brother of the Regulator of Imprinted
Sites” in 2002
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.
Theme 1. The role of CTCF and BORIS in
tumourigenesis: models and methods
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 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