nPOD ECM Working Group
The nPOD extracellular matrix working group (nPOD-ECM) is comprised of teams of researchers working together with the goal of investigating the role of extracellular matrix (ECM) in type 1 diabetes through the study of nPOD samples. Our three research teams include:
- Marika Bogdani, Benaroya Research Institute
- Charmaine Simeonovic and Christopher Parish, Australian National University
- Lydia Sorokin and Eva Korpos, the Institute of Physiological Chemistry and Pathobiochemistry, University of Muenster
Our groups have been working with nPOD to determine if specific changes occur in ECM surrounding and within the islets and lymphoid tissues during the development of T1D. Each group has focused on different ECM components and how they change in the pathogenesis of the disease. Although we study the involvement of the ECM in T1D from different angles, our areas of research are complementary. Thus, our combined work provides a more complete overview of events that take place in the ECM in T1D. We share the concept of collaboration and data sharing encouraged by nPOD as the best way to advance our knowledge and maximize the potential for development of comprehensive studies and obtaining robust results.
T1D results from an immune cell-mediated destruction of the pancreatic β cells, which takes place in a permissive inflammatory environment. At the site of insulitis, the ECM serves as a substrate for the trafficking of immune cells from the blood stream into the islet, but also acts as a barrier to inflammatory cells infiltrating the islet and leading to destruction of the β cells. However, the involvement of the ECM in the development of human T1D is not well understood.
Our focus is on the ECM molecules heparan sulfate/heparan sulfate proteoglycans, hyaluronan and molecules that associate with hyaluronan, laminins, and collagens, as well as on the enzymes that can modulate these ECM components. These specific components of the ECM are present in basement membranes and interstitial matrix surrounding and within the islets. Normally, at the level of the islets, they contribute to islet architecture and β-cell viability. Since all cells involved in the destruction of islets in T1D come into contact with ECM, we postulate that these components of the ECM may, in part, regulate key events in pathogenesis of T1D such as β-cell death, immune cell migration, proliferation and invasion, cytokine expression and release, and antigen presentation. Our collaborative efforts address the changes that these specific ECM molecules undergo during the pathogenesis of T1D by applying an integrated approach and the latest technical advances. The nature and role of the ECM in islet biology, insulitis and T1D pathogenesis represent a pioneering frontier in autoimmune diabetes research.
You can find a review of our ECM research, published in a 2014 issue of Current Diabetes Reports.