Principal Investigator
CurrentUrinary Tract Obstruction is a leading cause of pediatric chronic kidney disease and end stage renal disease. Apart from surgery to relieve the obstruction, no specific interventions can prevent or limit obstructive nephropathy (urinary tract obstruction-induced kidney injury and dysfunction). The renal urothelium represents the front line of defense to urinary tract obstruction and a novel target for the development of therapies to mitigate obstructive kidney disease. We found that congenital and acquired urinary tract obstruction triggers renal urothelium remodeling, including urothelial cell (UC) proliferation, Uroplakin expressing (Upk)-UC expansion and urothelial plaque formation. We demonstrated that depletion of Upk-UCs or their plaque during urinary tract obstruction accelerates parenchymal loss, renal dysfunction, and mortality, indicating that urothelial remodeling is a protective adaptation to urinary tract obstruction. The research efforts in my lab focus on defining the cellular and molecular mechanisms governing developmental patterning and repair of the renal urothelium. The identification and characterization of the cells and pathways responsible for these processes will provide a platform for the evaluation of treatment strategies designed to prevent or attenuate the effects of urinary tract obstruction.
