The current research areas/groupings are:
i. Bone marrow failure and related disorders
The principal research interest of Professor Inderjeet Dokal and Dr Tom Vulliamy is bone marrow failure (BMF) focusing on the genetics of the inherited BMF syndromes, particularly dyskeratosis congenita (DC). Their research has highlighted the important role of telomeres in humans and the consequences of telomere dysfunction including dysregulated human development, premature ageing, increased risk of BMF and cancer. Current research is focused on elucidating the biology of the many uncharacterized cases of DC, BMF, familial myelodysplasia/leukaemia (with Professors Jude Fitzgibbon and Jamie Cavenagh) as well as studies aimed at correction of the cell defect with the long term aim of developing new therapies for this group of patients.
ii. Brain tumours and neural stem cells
Professors Silvia Marino and Denise Sheer have developed a systematic strategy to identify critical genetic, epigenetic and gene expression features in brain tumours. Key discoveries include RAF fusions in pilocytic astrocytomas, microhomology at the RAF fusion breakpoints, MYB abnormalities in certain grade II astrocytomas (Sheer) and the identification and elucidation of the role of PcG group genes in medulloblastoma and high grade glial tumours (Marino). Ongoing studies include exome sequencing, DNA methylation and histone mark profiling with a view of understanding the neural stem cell as cell of origin of brain tumours and identifying novel targets for treatment via studying the basic biology of brain tumours.
iii. Children’s environmental health and respiratory disease
Professor Jonathan Grigg’s environmental research is focused on our local population. The “Exhale” study is measuring changes in lung function and biomarkers of exposure to air pollution in primary school children over a 5 year period–coinciding with the introduction of the London low emission zone. Laboratory studies are assessing the mechanisms underlying the increased vulnerability to pneumococcal pneumonia in children exposed to particulate air pollution. In our NHS patients research is focused on treatment of preschool wheeze, difficult asthma and the prevalence of obstructive breathing in patients with sickle cell disease (Dr Paul Telfer).
iv. Colorectal cancer
The major interest of Professor Andrew Silver and Mr Mohamed Taha is colorectal cancer. This includes the identification of susceptibility genetic variants and modifiers of colorectal cancer (CRC) severity, and use of biomarkers of risk and outcome to facilitate stratified management in the clinic. Current studies are focussed on early onset CRC and the potential mechanistic links between type 2 diabetes and the risk of developing CRC. The genomics approach is also being applied to other types of gastro-intestinal cancers including oesophageal cancer with Professor David Kelsell. In collaboration with Dr James Lindsay the colorectal team have a strong programme of research in inflammatory bowel disease (IBD). This includes the identification of tissue and serum-based biomarkers for early detection of lesions in ulcerative colitis and fibrosis in Crohn’s disease. The group is also investigating the use of specific Histone deacetylase inhibitors for use in IBD control.
v. Developmental alterations in Down syndrome
Identification of molecular pathways altered by trisomy 21, leading to new insights into biology of Down syndrome (DS) is the long term research theme of Professor Dean Nizetic and Dr Jurgen Groet. This team identified the deregulation of embryonic stem cell fate and a new concept explaining how this de-regulation could be responsible for the increased leukaemia risk in DS children .This team generated the first induced-pluripotency-stem-cells (iPSC) within the Blizard Institute, establishing a unique isogenic DS iPSC model.
vi. Diabetes and obesity
Professor Graham Hitman’s principal research is on diabetes and obesity in people from South Asia focussing on genomics (genetic and epigenetic) and prevention strategies in high risk populations. For example one current program includes genomic and lifestyle predictors of foetal outcome relevant to diabetes and obesity in South Asians living in Europe or their home countries. This work also has a complementary interface with other investigators in the Centre (Professors Vardhman Rakyan and David van Heel) and that of Primary Care and Public Health (Professors Khan and Thangaratinam).
The overall goals of the groups led by Professor Vardhman Rakyan, Doctors Miguel Branco, Ann O’Loghan and Yung-Yao Lin, are to understand the molecular basis of the non-genetically determined component of mammalian phenotypes and diseases. Within this context the Rakyan group has a particular interest in ‘epialleles'–loci at which the epigenetic state varies as a result of stochastic, genetic and/or environmental influences. Several complementary lines of investigation are pursued to integrate molecular genomics, computational biology, mouse models, and human cohorts to understand the role of epialleles in complex phenotypes and diseases, transgenerational epigenetic inheritance, and environmental epigenomics.
The Branco group is investigating DNA methylation as well as its enzymatic oxidation derivatives (e.g. hydroxymethylation) with a particular interest in the targeting of retrotransposable elements by epigenetic modifiers and how this impacts on the host’s genome.
The O’Loghan group is investigating the role of the epigenetic complex PRC1 (Polycomb Repressive Complex 1) in repressing important tumour suppressors such as the INK4a/ARF locus. There is also interest in the function of PRC1 components, in particular the polycomb protein CBX7, in maintaining stem cell pluripotency and inducing cellular differentiation.
viii. Human autoimmune diseases
The principal research interest of Professor David van Heel is human autoimmune diseases (Coeliac disease, type 1 diabetes and Crohn's disease), and the functional consequences of genetic variants on human biology. Significant discoveries have included the identification of 40 new risk variants for Coeliac disease, understanding the overlap between autoimmune diseases, and probing the role of rare variants. Professors David Van Heel and Richard Trembath have been recently awarded a Wellcome Trust Strategic Award to sequence East London populations to identify volunteers carrying homozygous rare loss of function variants (“human knockouts”) and recall them for deep phenotyping, a project that will play a key role in Queen Mary’s proposed new Life Sciences Institute. Professor David van Heel directs the Barts Genome Center; this ensures a comprehensive genomics platform for all investigators in the Centre and Institute wide.
ix. Neonatal medicine
The major emphasis of neonatal research has been the study of determinants of adverse outcomes following extremely preterm birth. This has involved long term collaborations between Professor Kate Costeloe and other institutions: the EPICure studies with Professor Marlow and studies of lung function with Professors Stocks and Dezateux. Other areas include the role of probiotics (Professor Kate Costeloe, Drs Shahid Hussain and Paul Fleming) in prevention of complications of prematurity in collaboration with the Dept of Microbiology in Barts Health, the use of Doppler ultrasound to study the neonatal circulation, particularly in relation to necrotizing enterocolitis (Dr Steve Kempley), mechanisms of placental transfer of nutrients, retinopathy of prematurity (Drs Shahid Husain, Ajay Sinha) and hypoxic ischaemic encephalopathy (Dr Divyen Shah).
x. Neuromuscular disorders
Professor Marino’s group is interested in the biology of the adult skeletal muscle stem cells and progenitor cells, on the pathways and genes involved in control of their maintenance, proliferation and differentiation, in particular the Polycomb group genes (PcG). We are particularly interested in assessing how fine tuning of the expression of these genes can be exploited to enhance the regenerative function of the skeletal muscle in chronic neuromuscular disorders. The Lin group is investigating the molecular and cellular mechanisms underlying allelic variants of muscular dystrophies, focusing on the key components of the dystrophin-associated glycoprotein complex (DGC) and genetic modifiers of the DGC. Current research strategies have employed cellular reprogramming and genome editing technologies with the long-term aim of developing new therapeutic interventions. Prof Marino and Dr Lin collaborate on a project aiming at applying PcG gene modulation to Duchenne Muscular Dystrophy.
xi. Paediatric infection and immunology
Dr Andrew Prendergast’s group has a focus on the interaction between infection, immunity and malnutrition, particularly in the context of HIV infection. Specifically, his group is investigating the role of microbial translocation, a pathological process that underlies two conditions of global public health importance: childhood malnutrition and HIV infection. Laboratory investigations of the causal pathway linking poor sanitation/hygiene and impaired growth in infancy and the link between the gut microbiota and growth are being explored.