Research Interests
We are interested in understanding how hormones and environmental cues regulate cell metabolism, with a specific focus on insulin-regulated glucose transport into fat and muscle cells.
One of the ways in which insulin lowers blood glucose is through stimulating glucose transport into adipose and muscle tissue. Insulin activates a signal transduction cascade in these tissues to promote the translocation of the glucose transporter GLUT4 from specialised intracellular storage vesicles to the plasma membrane, facilitating glucose uptake. We currently have an incomplete understanding of the signalling events and trafficking processes that control the redistribution of GLUT4. One of the objectives of our work is to fill in these knowledge gaps.
The reason we want to increase our understanding in this area is that impaired insulin-stimulated glucose transport in muscle and fat is a major contributor to whole body insulin resistance – a state where insulin no longer efficiently lowers blood glucose and a risk factor for type 2 diabetes. There is currently no consensus on the molecular basis for impaired insulin responses in these tissues, and there are no treatments that specifically target this pathway. We aim to shed light on how the insulin signalling network and GLUT4 trafficking apparatus are altered in insulin resistance, and identify new therapeutic targets.
Research Approach
We take an interdisciplinary approach using cell culture and in vivo models to study insulin action, GLUT4 trafficking and glucose metabolism. We take hints from ‘omics (human genetics, proteomics) data to find novel genes/proteins that play a role in insulin action, insulin-stimulated GLUT4 trafficking and/or insulin resistance.
We have established methods to screen many genes-of-interest for roles in specific metabolic processes. For example, we assay insulin-stimulated endogenous GLUT4 translocation using high-content imaging, and continue to develop new ways to study distinct aspects of GLUT4 trafficking (e.g. delivery to the cell surface, internalisation). We use our expertise in molecular (e.g., manipulating gene expression) and cell biology (e.g., microscopy) and biochemistry (e.g., subcellular fractionation, immunoprecipitation) to study how proteins-of-interest regulate insulin responses and the GLUT4 pathway in health and disease.
Group Members
Dr Delia Cicciarello, Research Associate
Dr Dilip Menon, Research Associate
Eleanor Fox, PhD Student
Meghna Birla, PhD Student
Leontina Koleva, MPhil Student
Research Funding
MRC project grant
UKRI Cross Council Research Grant
Wellcome Discovery Award
