Research Profile

Diabetes can result in damage to many organs, including the kidney, leading to diabetic kidney disease. High glucose damages the blood vessels as well as the podocytes in the kidney, resulting in kidney failure. Stem cells and their derived extracellular vesicles have been proven to effectively reduce cellular injury during diabetes. Therefore, in this project we will be investigating a recently discovered stem cell type that is collected from human urine, called urine derived stem cells (USCs), for treating diabetes. Due their painless collection, high expandability, self-renewal capacity, renal origin, and multi-differentiation potential, USCs are ideal candidates for stem cell-based therapies for kidney injury. Stem cells act via multiple mechanisms, including through paracrine signaling by releasing extracellular vesicles (EVs) including exosomes. EVs have high specificity due to membrane proteins that interact with target cells upon contact, therefore kidney stem cell-derived EVs have the greatest potential for effectively treating kidney diseases. The project will investigate the capability of extracellular vesicles released by USCs (USC-EVs) to prevent diabetes-related kidney injury. The podocytes will be given high glucose to simulate the diabetic environment, treated with USC-EVs and analyzed for reduction in cellular injury and apoptosis. The project will utilize both animal and human diabetic kidney disease models to develop a clinically translational approach. We expect that the USC-EVs will improve kidney and podocyte structure and function and will lead to an effective prevention approach for diabetic kidney disease.

During diabetes, the presence of high glucose from too much sugar in the blood can damage kidneys by killing off the blood filtering cells in the kidney called podocytes. We will test a new treatment for diabetic kidney disease that is based on stem cells. Stem cells can help support the cells in the kidney during injury. The stem cells secrete small messaging signals called extracellular vesicles (EVs) that enter other cells easily. The EVs can carry many types of messages, or cargo, between cells. One of the main advantages of developing EVs as a drug is that they do not cause the body to have an immune reaction, so collecting the stem cells from the recipient or matching blood types is not necessary. In this project, we want to test EVs from stem cells grown from the living cells found in human urine, called urine-derived stem cells (USCs). Because USCs come from kidney, we believe EVs from USCs (USC-EVs) can target and reduce kidney injury during diabetes better than other cell sources of EVs. We have successfully grown USC-EVs and made podocytes from stem cells that were created from skin samples. We confirmed that adding glucose sugars injures the podocytes. We will first test if USC-EVs can stop cell death in high glucose-injured podocytes on a dish. Next, we will use a diabetic mouse model to confirm the effect seen on cells. We believe USC-EVs will reduce damage to diabetic kidney in mice. Successful completion of this project can help preventing diabetic kidney damage in patients.

Diabetes research holds great significance in my personal life as my father battles through diabetes, which impacted our family in several ways. Witnessing my father’s struggle to maintain his health the last few years has ignited my desire to work in the diabetes field. I believe that more advanced and novel approaches may offer preventative approaches for diabetes and ultimately leading to a cure for this devastating disease. The loss of my uncle’s life due to a complication of diabetic kidney disease motivates me as well. I approach my work with a sense of urgency for advancements in either controlling or preventing the complications of diabetes. I hope my research through the ADA fellowship will lead to interventions to alleviate diabetic kidney disease and help the patients and families affected by diabetes.

Advanced technologies as well as improved understanding of the disease had made promising improvements in the field of diabetes research. Better monitoring approaches for individuals has improved personalized treatment strategies yielding efficient results. In addition, the exploration in the research of beta cell regeneration, immunotherapies, as well as stem cells holds potential for effective interventions. I believe if we can continue collaboration between research scientists, healthcare professionals, and the patient community, then there will be better outcomes in near future.