Stephen O’Rahilly

As a physician-scientist I study the aetiology and pathogenesis of human metabolic and endocrine disorders. In particular I have been interested in identifying the genetic factors underlying susceptibility to conditions such as obesity, type 2 diabetes and other syndromes characterised by perturbations of insulin action. While continuing to contribute to studies addressing the genetic basis of common forms of these disorders, I have been particularly concerned with identifying extreme human phenotypes where highly penetrant pathogenic alleles are more readily identified. My colleagues and I study the effects of such mutations in heterologous cellular systems and in transgenic mammalian models as well as examining the impact of the genetic variants on the in vivo physiology of the patients themselves. In the area of obesity our work has illustrated that obesity might be most usefully viewed as a heritable neurobehavioral disorder, rather than a metabolic one. The research has aided the development of effective targeted therapy for certain rare subtypes of human metabolic disease.