Due to the generous donation of a donor, this project is now fully funded.
In type 1 diabetes (T1D) the body’s immune system recognizes, attacks, and ultimately kills the insulin-producing beta cells in the pancreas. During this process, the immune system releases many inflammatory molecules. One is 12(S)-HETE. It activates the GPR31 receptor on the beta cells. Published data, and our preliminary experiments, lead us to believe this activated inflammatory molecule causes the beta cells to malfunction and ultimately die.
Our goal is to discover molecules to block 12(S)-HETE from activating GPR31 to potentially protect the beta cells. We will use high throughput screening to monitor the activation of GPR31 in cells by testing thousands of molecules for their ability to block this activation. We refer to the successful drug-like molecules as GPR31 inhibitors.
To confirm our candidate GPR31 inhibitors will work in humans, we will use human pancreatic islets isolated from donors, or grown in laboratories. We will expose these human pancreatic islets to conditions that mimic the assumed 12(S)-HETE to GPR31 pathway which may cause the onset of T1D. We will test our candidate GPR31 inhibitors for their ability to protect human pancreatic islets before and soon after the initial attack on the beta cells.
Very little is known about GPR31. We will learn more about this molecule and shed light on the activation signaling and functional pathways relating to its interaction with 12(S)-HETE and the onset of T1D. While our focus is on protecting pancreatic beta cells, GPR31 is also present in other organs and tissues where its inhibition may also be therapeutically beneficial.