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Hodson Group: Cellular Metabolism and GPCR Signalling

Oxford Centre for Diabetes, Endocrinology and Metabolism

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.

 

Our team

Related research themes

Our focus is on finding the causes of metabolic and endocrine disease and capitalising on these discoveries to yield new treatments. We are world leaders in both large-scale genetic studies and global clinical trials, taking an international approach to advance our understanding and treatment of type 1 and type 2 diabetes. From target discovery for type 2 diabetes and probing the biochemistry of fat, through to understanding islet physiology and transplantation, investigating liver disease and unravelling the mechanisms behind rare endocrine tumours, our research truly spans the bed to bedside journey.
Diabetes, Metabolism and Endocrinology
Building on critical findings from our research streams, we are initiating new drug discovery programmes. Many of our researchers are engaged in target discovery and target validation research – elucidating molecular pathways that can be manipulated for disease modification.
Experimental Therapeutics
Using a range of imaging modalities, our researchers can probe – at the molecular level – the events that underpin cellular health and dysfunction.
Cellular and Preclinical Imaging
We seek to bridge the ‘innovation gap’ between ‘basic’ research in the laboratory and tangible benefits for patients. Our researchers aim to develop novel approaches to treating disease and we have particular strengths in evaluating technologies such as antibody therapy and gene therapy, and using new techniques for target discovery. Many of our researchers collaborate with biotech and industry partners to accelerate progress along the drug discovery pipeline and assess these new treatments in the clinic.
Emerging Therapies and Drug Discovery
A raft of cellular and molecular biology techniques underpin much of the work we do to elucidate the mechanisms of disease. We use established techniques to answer new questions and also develop our own novel and unique methodologies to drive further innovation.
Cellular and Molecular Biology