Brian injury, neuroprotection and genetics
This work has included developing an award-winning regional service for neonatal neuroprotection in the East of England. The Cambridge NeuroNICU, modelled on a service led by Professor Rowitch at UCSF, is a clinical and research platform for infants at risk of brain injury from across the region. This includes an infant brain functional imaging facility run by Professor Topun Austin that combines MRI with optical and electrophysiological technologies to identify infants at risk of brain injury through neoLAB, a joint venture with University College London (www.neoLABresearch.com). There are active collaborations with Departments of Psychology (Dr. Vicky Leong), Department of Psychiatry (Professor John Suckling) and Autism Research Centre (Professor Simon Baron-Cohen).
Professor David Rowitch and his team investigate precision medicine focusing on applications of genomic technologies to diagnose and better understand the biological basis and rational treatment of neonatal neurological disorders including encephalopathic seizures and cerebral palsy. His laboratory investigates diversity of glial cells and patient derived models of leukodystrophy
Diabetes and Obesity
Primary prevention and improved treatments for children
In 2008, Professor Dunger and his team launched the first international study of the use of ACE inhibitors and statins in adolescents with Type 1 diabetes (TID) based on extensive preliminary observational data involving over 10,500 young people with diabetes and their parents. Other on-going studies of TID include the role of the growth hormone – IGF1 axis in the development of insulin resistance, and the place of growth hormone inhibitors in preventing diabetic complications.
The clinical testing of closed-looped insulin delivery in T1D, using algorithms developed by Dr Roman Hovorka, is showing promising results. Under supervised conditions, overnight closed-loop reduced the risk of nocturnal hypoclycaemia and improved glucose control. The first-ever home study will adopt an in-house prototype system which has received regulatory approval. Dr Kathy Beardsall investigates continuous glucose monitoring and early insulin replacement in preterm infants in NICU and impact on long term outcomes.
Genetics and pathophysiology of severe childhood obesity
Professor Sadaf Farooqi has recruited over 7000 children with severe obesity to the Genetics of Obesity Study (GOOS). She is using exome and genome sequencing to identify rare variants that are enriched in severely obese children as well as computational and molecular approaches to finding the mechanisms that are disrupted in severe obesity. She runs a programme of translational research looking into the complications of severe obesity in childhood.
Inflammation, Epigenetics and the Microbiome
Another area of research is focused on epigenetics of the intestinal immune system in health and disease particularly inflammatory bowel diseases (IBD) led by Dr Zilbauer. Specifically, we are currently exploring the impact of epigenetic mechanisms such as DNA methylation and histone modifications on regulating gene expression in purified cell subsets such as the intestinal epithelium as well as peripheral blood mononuclear cells (PBMCs)
As part of a study to investigate pathophysiology of gut barrier dysfunction in critical illness, Dr Nazima Pathan and the PICU research group are undertaking research into how the gut-host homeostasis is altered in critical illness in children for insights into disease complications and therapy. The PICU team has an interest in genomic applications and neuro-intensive care.
Genetics and development of paediatric cancers
The NHS paediatric haematology and oncology team is truly multidisciplinary and requires vital inputs from many individuals to allow the delivery of high quality patient care as part of clinical research trials. From a laboratory research perspective, Dr Matthew Murray’s translational programme involves the study of genetic changes in solid tumours of childhood, with a particular focus on germ cell tumours (both extracranial and intracranial). He has identified that the same genetic changes seen in germ cell tumours may also be found in patient bloodstream at the time of diagnosis, offering the potential to improve the accuracy of diagnosis, disease-monitoring and follow-up.
Epidemiology and Population Science
Genetic epidemiology and cohort studies
Professor Ken Ong and Professor Dunger study genetic, environmental determinants of size at birth, future growth and risk for adult disease. Current studies include study of the role of imprinted genes led by Dr Clive Petry and detailed evaluation of the effects of nutrition during infancy on short term risk for obesity and insulin resistance.
Early growth and puberty timing as predictors of disease risk
Studies on mammalian sex development are applied to the management of infants with disorders of sex development (DSD), including the effects of environmental variants in genes controlling androgen production and action appear to affect normal development, including growth at puberty. Much of this research is underpinned by the Cambridge Baby Growth Study (CBGS) established by Professor Hughes and Dr Carlo Acerini in 2001, with over 2000 families recruited. Recent study explores role of putative endocrine disruptors in the development of common DSD such as hypospadias.
‘Next Generation’ Projects
With new funding from the NIHR Cambridge Biomedical Research centre, we are collaborating with Professor Gordon Smith to follow up growth and neurodevelopment of infants from Predictors of Pregnancy outcome study (POPS). With Professor Lucy Raymond, Dr. Helen Firth and Dr Matthew Hurles (University of Cambridge and Wellcome Trust Sanger Institute) we are investigating utility of whole genome sequencing in the NICU and paediatric ITU and genotype-phenotype linkage to electronic health and educational records to assess long-term outcomes into adulthood.
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