Karpe, Hodson and Christodoulides Group: Metabolic Research Group
We apply an integrated approach to human metabolic disease which involves genetic, genomic, cell biology and whole body metabolic studies to understand the pathogenesis of the complications of obesity such as fatty liver disease, type 2 diabetes and cardiovascular disease.
Scientists, postdoctoral staff and students from a mixture of clinical and non-clinical backgrounds are trained in all key investigation areas. The group has a number of platforms to support its integrated work. These include the 8,000 participant strong and extensively phenotyped and genotyped Oxford Biobank, a dedicated analytical mass spectrometry lab for analysis of metabolic tracers, direct access to the OCDEM clinical research unit and a cell biology lab with unique access to a range of human tissue-specific cell lines. The key areas of investigation are:
- Fatty liver disease: Our studies are directed toward understanding how perturbations in liver fat metabolism impact on metabolic health and risk of cardiovascular disease and type 2 diabetes. Using a combination of human in vivo, ex vivo and in vitro cellular models, in combination with metabolic tracers (stable-isotopes) the role of phenotype, genotype and nutritional factors on liver fat metabolism are investigated.
- Human fat distribution: We are working to understand why lower body fat, as opposed to upper body fat accumulation, is protective against type 2 diabetes and cardiovascular disease. We perform functional genetic studies to translate gene variants associated with the fat distribution traits. We perform human in vivo studies to understand the trafficking, storage fat in and between adipose tissues.
- Wnt signalling in adipose tissue: We use human genetic and physiological approaches, accompanied by functional studies in human fat depot-specific cellular models to better understand the mechanisms whereby Wnt signalling modulates adipose tissue biology and thereby susceptibility to obesity and obesity-associated metabolic diseases.
Emerging areas are:
- Brown adipose tissue function
- Ethnicity, fat distribution and its link with global disease burden
- Metabolic tissue cross-talk
- Nutrient-specific effects on liver and adipose tissue metabolism
Health selection into neighborhoods among patients enrolled in a clinical trial.
Arcaya MC. et al, (2017), Prev Med Rep, 8, 51 - 54
The ‘molecularly unstratified’ patient: a focus for moral, psycho-social and societal research
Hordern JWS. et al, (2017), Biomedicine Hub
The β-cell assassin: IAPP cytotoxicity.
Raleigh D. et al, (2017), J Mol Endocrinol, 59, R121 - R140
Quantification of transmission risk in a male patient with a FLNB mosaic mutation causing Larsen syndrome: Implications for genetic counseling in postzygotic mosaicism cases.
Bernkopf M. et al, (2017), Hum Mutat, 38, 1360 - 1364
Clinical studies and trials
- The Oxford Biobank is a randomly selected population-based local cohort of healthy 30-50 year old men and women who have given informed consent to take part in future research projects involving for example the ‘recall-by-genotype’ or recall-by-phenotype’ approaches.
- A cohort of patients with newly diagnosed type 2 diabetes. This is currently being established using the same phenotyping platform as the Oxford Biobank
- A cohort of patients with familial partial lipodystrophy
- Specific nutrient intervention studies