The Carlton M. Bates laboratory conducts studies primarily on the role 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 laboratory is actively elucidating the molecular pathways through which Fgfrs pattern developing bladder urothelium and repair postnatal urothelium after injury.
The lab has recently discovered novel critical links between Fgfr signaling and glucose metabolism in developing nephron progenitors. The lab is also collaborating with others at the University of Pittsburgh on regenerating functioning kidney tissues from mouse progenitors and human induced pluripotent stem cells in ectopic sites such as the lymph node. These approaches may lead to new biomarkers and therapies for congenital kidney and lower urinary tract disease.
Zhao H, Kegg H, Grady S, Truong H, Robinson M, Baum M and Bates CM. Role of fibroblast growth factor receptors 1 and 2 in the ureteric bud. Developmental Biology, 276 (2): 403-415, 2004
Pitre D, Kish K, Kutay B, Kegg H, Zhao H, and Bates CM. Role of fibroblast growth factors 1 and 2 in the metanephric mesenchyme. Dev Biol, 291 (2) 325-339, 2006.
Sims-Lucas S, Argyropoulos C, Kish K, McHugh K, Bertram JF, Quigley R, Bates CM. Three-dimensional imaging reveals new ureteric and mesenchymal defects in Fgfr2 mutant kidneys. J Am Soc Nephrol, 20 (12): 2525-33, 2009. PMCID: PMC2794230
Hains DS, Sims-Lucas S, Carpenter A, Saha M, Murawsik I, Kish K, Gupta I, McHugh K, Bates CM. High incidence of vvesicoureteralreflux in mice with deletion of fibroblast growth factor receptor 2 in kidney mesenchyme. J Urol, 183(5): 2077-84, 2010. PMCID: PMC3657704.
Sims-Lucas S, Cusack B, Eswarakumar VP, Zhang J, Wang F, Bates CM. Independent roles of Fgfr2 and Frs2α in ureteric epithelium. Development. 138: 1275-1280, 2011. PMCID: PMC3050660.
Sims-Lucas S, Di Giovanni V, Schaefer C, Cusack B, Eswarakumar VP, Bates CM. Ureteric morphogenesis requires Fgfr1 and Fgfr2/Frs2a signaling in the metanephric mesenchyme. J Am Soc Nephrol, 23(4): 607-17, 2012. PMCID: PMC3312502.
Di Giovanni V, Walker KA, Bushnell D, Schaefer C, Sims-Lucas S, Puri P, Bates CM. Fibroblast growth factor receptor-Frs2a signaling Is critical for nephron progenitors. Dev Biol, 400(1): 82–93, 2015. PMCID: PMC4361332.
Puri P, Bushnell D, Schaefer CM, Bates CM. Six2creFrs2α knockout mice are a novel model of renal cystogenesis. Sci Rep, 6: 36736, 2016. PMCID: PMC5113122
Ikeda, Y, Zabbarova I, Schaefer CM, Bushnell DS, de Groat WC, Kanai AJ, and Bates CM. Fgfr2 is integral for bladder mesenchyme patterning and function. Am J Physiol Renal Physiol, 312(4): F607-F618, 2017. PMCID: PMC5407073.
Puri P, Schaefer CM, Bushnell D, Taglienti ME, Kreidberg JA, Yoder BK, Bates CM. Ectopic phosphorylated Creb marks dedifferentiated proximal tubules in cystic kidney disease. Am J Pathol, 188(1), 84–94, 2018. PMCID: PMC5407073