1. Elena Klenova CTCF and BORIS in normal development, epigenetics and tumourigenesis Areas of research: Molecular Oncology Gene regulation Translational research : clinical links via EBSI

2. CTCF and BORIS CTCF, named for “CCTC binding factor” in 1990 BORIS, for “Brother of the Regulator of Imprinted Sites” in 2002 Transcription factors with common DNA – binding domain: Normally expressed in testis Ubiquitously expressed

3. CTCF and its known modifications and interacting partners Ohlsson et al, 2010

4. CTCF plays an important role in the regulation of nuclear architecture: Genome-wide CTCF-mediated chromatin interactome Handoko et al., 2011

5. 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.

6. 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

7. 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.

8. 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