The Thurmond Lab’s focus encompasses research into SNARE-mediated vesicle trafficking events and cytoskeletal signaling as they pertain to the causes of diabetes. We have discovered that people with diabetes harbor defects and deficiencies in certain vesicle trafficking proteins. We are actively devising strategies to remediate these defects.
The proteins that we study — syntaxin 4 (STX4), p21-activated kinase (PAK1) and Doc2b — play significant roles in insulin production, as well as insulin and glucose uptake by skeletal muscle and fat tissues. We have found that depleted STX4 and PAK1 reduce insulin release and sensitivity, while overexpression of STX4 and Doc2b lead to improved glucose control. We are exploring therapeutic approaches that can restore or raise STX4 and Doc2b levels to increase insulin secretion and overcome insulin resistance among diabetes patients and those at risk of developing type 1 or type 2 diabetes.
Another goal is to make islet cell transplantation available to more patients. We are zeroing in on STX4 — which has the ability to activate dormant insulin-producing beta cells — to determine whether we can take advantage of the protein’s action to modify the islet cell transplant so that it uses fewer cells. Success in this endeavor would make possible more transplants from the limited resource of cells donated by humans.
The Thurmond Lab also is examining STX4 and PAK1 as potential biomarkers for diabetes. If these proteins can help us to detect early diabetic changes, patients can receive more timely interventions that preserve islet cell function and improve blood glucose control. A related project meant to expand our understanding of diabetes is exploring how production and use of STX4 and PAK1 are influenced by risk factors such as obesity, inflammation or a diet high in fat and sugar.