The Carlton M. Bates laboratory focuses primarily on the roles of fibroblast growth factor receptors (FGFRs) and their signaling adapter proteins in kidney and lower urinary tract using the mouse as a model. These studies are clinically relevant given that congenital abnormalities of the kidney and urinary tract are responsible for the majority of cases of chronic kidney disease in children. Using various gene-targeting approaches, the laboratory has revealed how FGFRs and their adapters are critical for temporal patterning of multiple renal and bladder tissue lineages. The Bates laboratory has generated mouse models of pediatric structural kidney and lower urinary diseases, including obstructive nephropathy, renal aplasia/dysplasia/hypoplasia, vesicoureteral reflux and reflux nephropathy, progressive cystic kidney disease, atonic bladders, and functional bladder obstruction.
The recent major focus in the laboratory is on how FGF7/FGFR2 signaling acts in the context of bladder urothelial injury. The laboratory has evidence that exogenous FGF7 blocks Cyclophosphamide-induced apoptotic death of deeper urothelial cells, accelerates regeneration of outer Superficial cells and leads to faster and high fidelity repair compared to vehcile-treated mice. The team also has evidence that endogenous FGFR2 signaling blocks pathological endoreplication of urothelial Basal progenitor cells after Cyclophosphamide injury. Loss of a one or two allele loss of FGFR2 in urothelium of mice leads to regeneration defects that last even until six months after injury. Mutant and control mice (to a lesser exent) have ectopic progenitor cells that may predispose to urothelial cancer long after Cyclophosphamide. The lab is interested in understanding how FGFR2 signaling acts on urothelium in the context of other injuries (radiation, infection, volume overload) and how other pathways that regulate the cell cycle and DNA repair affect the response to various urothelial injuries.