Cellular function fully depends on DNA integrity, which must be preserved, at great metabolic and other cost, for the entire lifespan of an organism. DNA is constantly threatened by damage and its futile repair can lead to genomic instability, compromising transcription or interfere with replication and impinge on chromatin structure, thus affecting vital DNA-templated processes. Defects in the way cells repair or respond to different DNA damages are causatively linked to increased genomic instability and have been implicated in human pathology, heritable cancers, and syndromes with premature aging features as well as severe neurological and developmental abnormalities.

Our research focuses on the molecular, genetic and cellular dissection of genome maintenance mechanisms in humans and their role in ensuring proper development and protection against mental dysfunction or cancer.

In particular, our research is centred on the molecular mechanisms that couple arrest of active transcription to chromatin alteration and repair in healthy versus disease situations. To delineate these events, we employ advanced proteomics and high-throughput genomic approaches in combination with biochemical and cellular techniques in normal human cells and a large battery of patient-derived cell lines. Our ultimate goal is to identify the regulatory cascades involved in the interplay between genomic stability and active transcription and elucidate their role in preserving genetic and epigenetic inheritance. These studies are expected to provide valuable insights into the underlying causes of DNA damage-related disorders such as Cockayne syndrome and Xeroderma pigmentosum and explain their clinical features.

Moreover, our studies involve the exploration of the role of active transcription in chemotherapeutic agent-driven cytotoxicity.

In addition, the effect of tumor-driven chromatin modifications in gene expression, DNA repair efficacy and cellular chemosensitivity is under investigation.

 

Our work is funded by:

 

B.S.R.C. "Alexander Fleming"
34 Fleming Street, 16672 Vari, Greece
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