Project Two

Identifying the cellular and transcriptional pathways driving cell type differentiation, inflammation, and mitochondrial functions in the urothelium

PI: Cathy Mendelsohn, PhD

Dr. Mendelsohn’s lab uses mouse models to elucidate genetic and cellular events important for lower urinary tract development, homeostasis, and regeneration. Developmental studies currently underway are in collaboration with Ali Gharavi and Simone Sanna-Cherchi, focused on validated mutations in TBX6 and WNT5a and other candidates that we have identified in families with lower urinary tract anomalies. 

Dr. Mendelsohn’s lab is also interested in identifying cellular and molecular changes important for maintenance, regeneration, and repair of the urothelial epithelium. The urothelium is a multilayered epithelium that serves as a barrier between the blood and urinary tract. Urothelial cells rarely divide, but can rapidly regenerate in response to Urinary Tract Infection or chemical damage. Her project is focused on identifying the cellular and transcriptional pathways driving cell type differentiation, inflammation, and mitochondrial functions in the urothelium. They find that Pparg, a nuclear receptor, can reprogram basal cells to produce luminal cell types in situ, controls inflammation via Nfkb, and transcriptionally regulates the expression of carnitine transporters, that shuttle fatty acid into the mitochondrial matrix for oxidative phosphorylation. Recent studies from the Mendelsohn lab have identified the transcriptional and epigenetic networks downstream from Pparg that regulate important urothelia functions and cellular regeneration in a variety of benign (LUTS) and cancer disease models.