Research issue
Thanks to recent advances we now know the entire sequence of the human genome. The current challenge is to understand how the individual genes are regulated so that they are expressed in the right tissues at the correct time and levels. Aberrant regulation of the genetic information contributes to inherited forms of disease as well as to acquired forms such as cancer.
Our group is studying the molecular mechanisms responsible for regulating gene expression at the epigenetic level to identify novel markers for early disease detection and new targets for the development of innovative therapies.
What we are doing about...
1. Early Disease Detection markers
Sequencing of the human genome has revealed that only 3% of it codes for protein. More than half of the genome (about 55%) is composed of repetitive sequences. Despite their abundance these sequences have remained largely understudied because of the difficulties due to their repetitive nature. We are developing bioinformatics and technical tools that are allowing us to mine the repetitive sequences and identify individual repeats that have characteristics of molecular biomarkers.
2. Novel Therapeutic targets
We are investigating how genes (for example genes associated with inherited diseases such as anemia or tumor suppressor genes in cancer) are switched off to determine which proteins are responsible for the silencing. In addition we are studying why repetitive sequences become switched on in cancer and which proteins are involved in this activation. Activating and repressing proteins will then be potential targets for the development of novel therapies.
Outcomes
Identification of novel biomarkers
We have been working to identify novel biomarkers for early detection of cancer from the region of the genome that has been until recently overlooked, the repetitive part of the genome that has been until recently referred to as ‘junk DNA’. We have published .
Identification of transcripts driving epigenetic alterations and disease
Our group has focused on studying those diseases that are due to epigenetic causes that is caused by changes in expression of the disease gene that are not accompanied by mutations in the genomic sequence of the gene. We have .
More recently we have provided evidence that these effects are not restricted to inherited forms of diseases such as alpha thalassemia, but can also occur in cancer following activation of repetitive sequences (