Regulatory Genomics of Reversal of Diabetic Nephropathy

Diabetic nephropathy is the leading cause of end-stage kidney disease and dialysis in the United States. Within the kidney, the filtration barrier and especially its specialized epithelial cell, the podocyte, is particularly susceptible to diabetes-induced damage. The BTBR ob/ob mouse model of type 2 diabetes accurately recapitulates the progressive podocyte loss that is thought to underlie diabetic nephropathy. Interestingly, leptin administration reverses kidney injury and restores podocyte numbers in this model. Dr. Akilesh will use advanced genomic techniques (DNase-seq) and bioinformatic approaches to dissect the genomic regulation that underlies podocyte injury and regeneration in the BTBR ob/ob mouse model of diabetes. These studies will provide insights into mechanisms and approaches to reverse diabetic kidney injury in humans.