List of selected publications or full publications

Science (2005) 307:370-3 full text

Research Interests

The overall theme of research within the group is type 2 diabetes. In particular, we focus on two major components of type 2 diabetes, namely obesity and insulin resistance, and how these two phenomena interlink to predispose to metabolic disease. Our general aim is to provide a better molecular understanding of these disease processes so that improved therapy can be designed. We approach these issues in three general ways.

1. Human studies We have access to unique populations of subjects with extreme phenotypes of obesity and insulin resistance in addition to large populations relevant to the more common phenotypes of type 2 diabetes and obesity. Mutations which are detected in candidate gene studies are explored further for their role in human disease by linkage studies in pedigrees, functional studies of the properties of the mutant variant and detailed in vivo studies in humans.

2. Studies in cellular models We have extensive activities in functional genomics with a major focus of the laboratory on exploring the cellular consequences of mutations found in candidate genes in humans with diabetes related phenotypes. In addition, we undertake basic studies into the biology of insulin and IGF-1 signalling and adipogenesis, processes which inform our more applied work in humans.

3. In vivo models Recently we have begun to use murine models to explore certain aspects of the molecular pathogenesis of human diseases. This is a growing part of the programme.

Research group organization & structure

The research group is based in two locations. The majority of the group is in University of Cambridge embedded space within Addenbrooke’s Hospital Department of Clinical Biochemistry. The group that works on the genetics of obesity is located in the Cambridge Institute for Medical Research. The overall research programme is supported by a programme grant from the Medical Research Council on molecular mechanisms in obesity and one from the Wellcome Trust on molecular mechanisms of insulin resistance. We are also the lead group in the Wellcome Trust Integrative Physiology Consortium for the Study of Common Metabolic Disease which represents a major grant from the Wellcome Trust to support integrative physiology and links investigators in the University of Oxford with those in the University of Cambridge. In general, the research group is highly collaborative and we have key links, in particular with Dr Toni Vidal-Puig, University Lecturer in Clinical Biochemistry (in the area of animal models), Professor Krish Chatterjee, Department of Medicine (nuclear receptors and metabolism), Professor Ken Siddle, Department of Clinical Biochemistry (insulin signalling), Dr Nick Wareham, Department of Public Health (genetic epidemiology) and Dr Ines Barroso, Sanger Institute (genetics of diabetes and obesity). There are many shared projects, shared students, etc between these investigators.

Members of group

* Joint appointment with Professor K Siddle
° Joint with Dr A Vidal-Puig
† Joint with Dr N Finer

Contact: so104@medschl.cam.ac.uk
Phone: (44) 1223 336855
Fax (44) 1223 330598