Research Focus
Our laboratory is interested in the cell biology of the β-cells of the endocrine pancreas. Pancreatic β-cells play a key role in glucose homeostasis by releasing the glucose-lowering hormone insulin. Autoimmune destruction of β-cells leads to the development of type 1 diabetes mellitus, whereas impaired insulin secretion is implicated in the pathogenesis of type 2 diabetes mellitus.
Cell biology of β-cells
A major topic of interest is the biology on insulin secretory granules, which are the organelles devoted to the storage and regulated release of insulin in response to glucose and other stimuli. Specifically, we aim to understand how elevation of blood glucose levels, quickly stimulates the biogenesis of new secretory granules by up-regulating the production of insulin and other granule cargoes. We also work on the protein complexes that mediate the interaction of secretory granules with the cortical actin cytoskeleton. The dynamic assembly and disassembly of these complexes may regulate the fusion of secretory granules with the plasma membrane and the recycling of their membranes following exocytosis.
To pursue these studies, we apply a large variety of molecular, biochemical and imaging techniques ranging from molecular techniques (spatial transcriptomics), structural biology (volume electron microscopy) in vitro approaches (insulinoma cells and purified pancreatic islets) and in- vivo models (transgenic and knock-out mice).
P. Verkade, J. Ouwendijk, M. Solimena
Translational research on Type 1 diabetes
Certain viral infections are associated with autoimmune reactions against β-cells and the development of type 1 diabetes. These viruses include Coxsackievirus and SARS-CoV-2 (the virus that causes COVID-19). By understanding how these viruses impact the cell biology and antigen presentation of beta cells we hope to shed light on how they may also promote the autoimmune reactions that cause type 1 diabetes.
Translational research on Type 2 diabetes
We further aim to elucidate what causes the progressive demise of β-cells along the progression from normoglycemia to type 2 diabetes. The discovery of biomarkers and molecular mechanisms of β-cell failure shall improve its prevention as well as the development of earlier detection strategies and more effective treatments. For these reasons, we work together with surgeons and pathologists from the University Clinic Carl Gustav Carus to collect samples of pancreases from living donors who have also been metabolically profiled prior to pancreatectomy. These samples are contributed to the LIDOPACO biobank (Living Donor Pancreatic Cohort), which is an invaluable resource for our research. Find out more here LIDOPACO.