Hodson Group: Cellular Metabolism and GPCR Signalling
We investigate how cellular metabolism and GPCR signaling converge to influence energy homeostasis in the periphery and brain during health and metabolic disease. We develop novel tools and technologies that allow us to study cell and tissue function with exquisite accuracy and detail, and apply these approaches to both preclinical models and human tissue.
The lab is focused on developing and using novel technologies to address challenging problems in cellular metabolism, with translational relevance for patients. We have particular interest in glucagon-like peptide-1 (GLP1) and gastric inhibitory polypeptide (GIP) receptors, two related class B G protein-coupled receptors. Both receptors are involved in the regulation of glucose homeostasis, food intake and inflammation, and as such have become blockbuster drug targets. For example, stabilised GLP1 receptor agonists are used in the treatment of type 2 diabetes, have just been approved as the first non-surgical treatment of obesity, and have shown promise for the treatment of fatty liver disease, as well as neurodegenerative disease. While GIP receptors have gained less interest, recent studies have shown that agonists targeting both GIP receptors and GLP receptors have highly synergistic actions to lower blood glucose levels, as well as food intake. Thus, dual agonists simultaneously targeting both GLP1 and GIP receptors are likely to become the major future drug treatment for metabolic diseases such as diabetes, obesity and fatty liver.
Despite this, much remains unknown regarding GLP1 and GIP receptor signalling. Over the past decade we have been trying to understand GLP1 and GIP receptor localization and signalling. To this end, we use a multidisciplinary research approach- spanning chemical biology and advanced imaging- to provide detailed insight into the influence of GLP1 and GIPR receptor signalling on cell function and organismal homeostasis.
Alongside these studies, we are also interested in cellular heterogeneity, specifically how pancreatic beta cell states contribute to insulin secretion, as well as islet plasticity and robustness.
Throughout, we use relevant preclinical models and human tissue, including from patients. Our overarching goal is to inform the next generation of therapeutics for common metabolic diseases such as diabetes and obesity.