Genetics and Genomic Medicine Supervisors
Theme Leader: Professor Tim Aitman
The Genetics and Genomic Medicine Theme is a strategic priority for Imperial College and extends from gene discovery to its exploitation in cell biology and the development of new predictive, preventative and therapeutic approaches, including gene and cell-based therapies. The goal of the Genetics and Genomics Strategic Theme is to effectively link genetics and genomics to every medical specialty within the College. Through cutting-edge research, integration with medical care and training of clinical and non-clinical scientists, the Theme makes cross-Divisional contributions across all Faculties of the College.
Tim Aitman
Genetics and Genomic Medicine
Researchers in the Genetics and Genomic Medicine use state-of-the-art genomic technologies, such as microarray and next generation DNA sequencing platforms, to investigate the genetic basis of common human diseases, including diabetes and obesity, autoimmune kidney disease and systemic lupus, and heart failure. The Theme particularly encourages training of junior doctors in these research areas, as genomic approaches are likely to play an increasing role in disease diagnosis and management in the coming 10-20 years.
Further Information: http://www1.imperial.ac.uk/medicine/people/t.aitman/
Contact Details
Tel: +44 (0)20 8383 8336
t.aitman@imperial.ac.uk
Eric Alton
Optimising gene transfer to the lung in vivo
My group is interested in gene therapy for cystic fibrosis.(CF) I coordinate the UK CF Gene Therapy Consortium, a coming together of 80 clinicians and scientists at Imperial, Oxford and Edinburgh Universities with a common strategy in developing clinically relevant gene therapy for CF. We undertook Europe's first trial of gene therapy for any disease, and the world's first controlled trial of CF gene therapy in the lungs of these patients providing proof-of-principle for correction of the underlying molecular defect. We have recently recruited 200 CF patients into a longitudinal study to assess a large panel of novel biomarkers. This will be followed by a year long multidose clinical trial of non-viral based gene therapy, assessing for the first time whether this can alter clinically relevant outcome measures. In parallel, we are developing novel gene transfer vectors, including lentiviruses, which we are taking through preclinical studies, with a view to later clinical trials.
Further information on the Gene Therapy Consortium can be found at:
http://www.cfgenetherapy.org.uk
Further information: http://www1.imperial.ac.uk/nhli/respiratory/popgenetics/genetherapy/
Contact Details
e.alton@imperial.ac.uk
Tel: +44 (0)20 7352 8121 x3398
Terence Cook
Genetic susceptibility to immune complex glomerulonephritis
My major interest is in elucidating mechanisms of injury in glomerulonephritis. We have used a number of models of induced and autoimmune glomerulonephritis to explore the role of macrophages, antibodies, Fc receptors, complement and other mediators. We have also studied genetic influences on susceptibility to glomerulonephritis and to autoimmunity. We are currently investigating the genes that control macrophage activation and the contribution of these to crescentic glomerulonephritis.
Further information: http://www1.imperial.ac.uk/medicine/people/t.h.cook/
Contact Details
t.h.cook@imperial.ac.uk
Tel: +44 (0)20 8383 2009
Bill Cookson
Functional genomics of respiratory disease
Professor Bill Cookson and Professor Miriam Moffatt run the molecular genetics section within the NHLI. Their group seek to carry out innovative research into a range of respiratory diseases, utilizing the extraordinary resources and technological advances that have arisen from the human genome project. Their research includes large-scale genetic studies of asthma and COPD, studies of global gene expression in lung cancer, the use of DNA sequencing technologies to characterise the microbiome of the lungs in health and disease, and investigation of genome-wide methylation patterns in asthma and lung cancer.
Further information: http://www1.imperial.ac.uk/medicine/people/w.cookson/
Contact Details
w.cookson@imperial.ac.uk
Tel: +44 (0)20 7351 8144
Philippe Froguel
Integrated genomics applied to Type 2 diabetes and obesity
Contact Details
p.froguel@imperial.ac.uk
Tel: +44 (0)20 8383 3989
Hani Gabra
Functional Genomics and Molecular Therapeutics of Ovarian Cancer
I direct the Ovarian Cancer Action research centre, currently consisting of 45 researchers dedicated to translational research into improving outcomes for this difficult disease. I have research groups involved in understanding the biology of ovarian cancer tumour suppressor genes, and the biology of platinum resistance (the most important anticancer drug for ovarian cancer) linked to an active clinical trials group.
We have developed great resources and expertise in these areas over the last 5 years and we very much enjoy having bright committed fellows in our environment. Currently there is an excellent project in the area of the OPCML tumour suppressor gene therapy. We identified OPCML in 2003 and showed that it is ubiquitously inactivated in ovarian cancer and many other cancers by somatic methylation. We have discovered that this GPI anchored membrane bound TSG is a systems level negative regulator of at least 5 receptor tyrosine kinases, abrogating them by direct binding, cav-1 mediated internalisation and proteasomal degradation via poly-ubiquitination. Based on this understanding we have developed a recombinant protein therapy strategy which demonstrated potent anti-tumour effects in-vivo. Additionally OPCML sensitises cancer cells to receptor tyrosine kinase inhibitors. The proposed project links functional genomics, molecular therapeutics and combinatorial therapies for ovarian, breast and lung cancer into one focussed project.
Further Information
http://www1.imperial.ac.uk/medicine/people/h.gabra/
Contact Details
h.gabra@imperial.ac.uk
Tel: +44 (0)20 8383 4674
Jeremy Nicholson
Metabonomics
Contact Details
j.nicholson@imperial.ac.uk
Tel: +44 (0)20 7594 3195
Cancer Epigenetics
Cancer is associated with a multitude of genomic aberrations, which can lead to abnormal expression of oncogenes and tumor-suppressor genes. In addition to these genomic changes, there is also selection during tumorigenesis for aberrant epigenetic regulation that does not involve a change in DNA sequence, but results in a stable change in gene expression. These epigenetic changes include DNA methylation and chromatin regulation, including histone modification. Since such epigenetic marks are reversible, their maintenance enzymes are attractive targets for the development of epigenetic therapies. However, the activity of current epigenetic therapies in solid tumours remains uncertain and epigenetic therapies with greater specificity and less toxicity are required. Targeting epigenetic therapies to specific patient populations and specific tumour cell populations will be essential to maximise efficacy and to optimise clinical activity of these agents.
A variety of projects are available in the Epigenetics Unit: Defining the epigenetic landscape of tumours by analysing DNA methylation and chromatin regulation; Examining the impact of germline methylation variability on cancer risk and prognosis; Studying epigenetic regulation in tumour stem cells and identifying novel therapy targets. These projects will use a variety of techniques routinely in use in our unit including bisulphite DNA sequencing, microarray analysis of methylation and gene expression, chromatin immunoprecipitation and bioinformatic analysis.
Further information: http://www1.imperial.ac.uk/medicine/about/divisions/surgeryandcancer/divisionofcancer/cancer/epigenetics/
Contact Details
b.brown@imperial.ac.uk
Tel: +44 (0)20 7594 1804
Further information: http://www.csc.mrc.ac.uk/Research/Groups/GMC/MolecularCardiology/
Contact Details: stuart.cook@imperial.ac.uk Tel: +44 (0)20 8383 1346
