A Microfluidic platform for Enhancing Methylglyoxal Detection in Type 1 Diabetic Brain Tissue
Methylglyoxal (MG) is a highly reactive metabolite of glucose and a prominent marker of dicarbonyl stress is diabetes. Recent studies by Dr. Stokes’s lab implicate a role for MG in brain microvascular endothelial dysfunction, thrombosis, and increased infarct seen in type 1 diabetic mice following stroke. Given the importance of glycated proteins in diabetic pathology, Dr. Stokes’s work focuses on developing therapeutic strategies to decrease protein glycation in diabetes. Dr. Hollins’s lab has developed a microfluidic platform for selective capture of carbonylated proteins. The objective of this project is to use Dr. Hollins expertise in microfluidics to develop a microfluidic platform that enhances the analytical detection and measurement of methylglyoxal (MG)- glycated proteins in diabetic rodents tissues. We will develop the microfluidic enrichment platform and validate it using diabetic rodent tissues samples from Dr. Stokes’ research group. Key innovations for this project include the development of a microfluidic enrichment platform for MG-mediated protein adducts and the demonstration and biological application of two-dimensional carbonylated protein enrichment, a technique not possible with standard preconcentration approaches. The proposed research is timely and medically significant since diabetes is a leading and growing global health concern. Diabetic patients exhibit increased CVD risk, even with well-controlled blood sugar levels. Development of a method to enrich MG-glycated proteins for further analysis and allow for testing of the efficacy of therapeutic strategies designed to decrease this glycation could help reduce risk of stroke, myocardial infraction and other diabetic pathologies.
Principal Investigator: Hollins, Bryant -- Biomedical Engineering
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