The aim of our group is to provide a detailed knowledge of the mechanisms regulating gene expression in normal cell differentiation and in disease, information that is fundamental for the identification of new disease markers and for the design of novel drugs and therapies to tackle individual disease cases.
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.
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.
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.
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 pilot work to show that these sequences represent a rich source of potential biomarkers.
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 published work showing that aberrant expression in a direction opposite to that of the gene (antisense-RNA expression) can drive silencing of an otherwise normal alpha globin gene causing a form of anemia called alpha thalassemia.
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 (See publication.)
Cancer Research Nottingham
Centre for Genetics and Genomics
TECDetec bioinformatics tool for detection of transposable element chimeric transcripts
Division of Medical Sciences and Graduate Entry Medicine
The University of Nottingham, Royal Derby Hospital
Uttoxeter Road, Derby DE22 3DT
telephone: +44 (0) 1332 724622
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