Genomics and Cancer
Lead: Professor Denise Sheer
Since each cell in an organism contains the same DNA sequence, other features of genomes must determine the regulation of gene expression. We know that specific transcription factors and epigenetic modifications modulate gene expression, but three-dimensional chromatin structure also plays a role. Professor Sheer’s group has made significant advances that link higher order chromatin architecture to gene expression, and are conducting experiments to identify the key determinants of chromatin folding. The other major research area of the group is the molecular pathology of cancer. Cancer can be regarded as a genetic disease at the cellular level, since genetic abnormalities such as mutations and chromosome translocations underpin the process of tumorigenesis and cancer progression. It is important to recognise these abnormalities to understand the cancer process, and provide diagnostic and prognostic information to clinicians. Genetic abnormalities are now also opening new avenues for targeted treatment of cancer. The Sheer group have identified critical genetic abnormalities in many types of leukaemias and solid tumours, and recently made key discoveries on paediatric brain tumours.
Research in the unit is currently based on two inter-related themes: the structure and function of the genome, and the molecular pathology of paediatric brain tumours.
Higher order chromatin architecture
A central question in biology is how the genetic information is assembled, accessed and interpreted during the processes of development, cellular responses to the environment, and disease. Professor Sheer’s group is examining the relationship between the linear and 3D organisation of the genome and transcriptional regulation using two model systems:
- Transcriptional upregulation of the human Major Histocompatibility Complex (MHC) on chromosome 6 by Interferon-Gamma
- Genome-wide changes during neural differentiation.
Other studies include investigations into the role of CTCF and its paralogue, BORIS (CTCFL), in regulation of gene expression.
Paediatric brain tumours
Cancer research in Professor Sheer’s group is currently centred on a common type of paediatric brain tumour, called low grade astrocytoma. The group has developed a systematic strategy to identify critical genetic, epigenetic and gene expression features in paediatric low grade astrocytomas, in collaboration with Professor David Ellison, St Jude Children’s Research Hospital, Memphis, USA. Key discoveries made so far include RAF gene fusions in pilocytic astrocytomas, microhomology at the RAF fusion breakpoints, and MYB abnormalities in certain grade II astrocytomas. Ongoing studies include exome sequencing and DNA methylation profiling with a view to improving our understanding of the biology of these tumours and identifying new targets for treatments.
Prof. Denise Sheer (Group Lead)
Post-Doc Researchers and Fellows
Dr. Johan Aarum, Dr. Tania Corbett-Jones, Dr. Jennie Jeyapalan, Dr. Sheena Patel, Dr William Ogunkolade
Mr Alfred Hill, Miss Isabel Morley
News & Announcements
Genomic Medicine Seminars
Prof. Denise Sheer
firstname.lastname@example.org Tel: +44 (0)20 7882 2595 Fax: +44 (0)20 7882 2180
Mr Surinder Pal
email@example.com Tel: +44 (0)20 7882 8605 Fax: +44 (0)20 7882 2180
Centre for Neuroscience and Trauma
Barts and The London School of Medicine and Dentistry
4 Newark Street