Institute of Genetic Medicine
The Genetics of Paediatric Cancers
The identification of genes involved in cancer is a cornerstone of molecular oncology and has led to a vast improvement in our understanding of tumourigenesis, identified a wide variety of therapeutic targets, and in some cases led to dramatic improvement in patient survival due to subsequent targeted intervention. Global approaches to gene identification in adult cancers have identified mutations in a much larger number, and wider variety, of genes than previously expected. However, the causative changes in many childhood cancers, where mutation rates are an order of magnitude lower, remain less well understood, and additional methods, such as comparative analyses are likely to be particularly valuable. Historically, most of our cancer research has been on neuroblastoma, but recently we have using a transpositional mutagen called Sleeping Beauty to alter the incidence and latency of cancer formation in a mouse model of medulloblastoma, a malignant childhood brain tumour. This work, performed in collaboration with the Northern Institute for Cancer Research in Newcastle, has identified mutations in linked networks of transcription factors which control neuronal development and proliferation. These appear to underpin cancer progression in this model, and using both direct analyses of human tumours, and experimental manipulation of genes within these networks, we hope to identify the key genetic events involved in tumourigenesis and identify novel therapeutic targets. In addition, I am involved in several projects with a focus on colorectal cancer, and these are in collaboration with Professor Sir John Burn who is also within the Institute of Genetic Medicine.
Transcriptional Diversity: Form and Function
RNAs where the exon order is shuffled relative to the underlying genomic sequence were first identified over 20 years ago, but until recently have been assumed primarily to be rare errors of known transcriptional processes. However, advances in sequencing technologies have allowed the abundance and distribution of RNA species to be analysed at very high resolution, and we and others have now established that shuffled transcripts are not only common, they can be the most abundant transcripts from some human genes. In addition, they are often circular, are largely cytoplasmic, and several non-coding circular transcripts have recently been shown to act as micro RNA sponges, indicating that they can have important functions in gene regulation. Because these transcripts extend our current understanding of how genetic information is both processed and functions, it is important to establish how they are generated and roles for the vast majority of these transcripts remain to be established. We are currently using high depth sequencing techniques, direct experimental manipulation of individual genes, and gene knockdown approaches, to perform mechanistic and functional analyses in both human and murine cell culture models.
Dr. Abd Al Hassain PhD. Research Associate
Hani Al-Afghani. PhD Student
Ginikachukwu Izuogo. PhD Student
Lisa Redford. PhD Student
Harsh Sheth. PhD student
Module Leader: BGM2058 Phylogenetics and Evolution.
Lecturer: BGM2057The genome: cell cycle, organisation, expression and function.
Lecturer: MMB8029 Medical Genomics.
Lecturer: MMB8031 Developmental Genetics.
MRes Strand leader: Medical Genetics.