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Lipschutz Research Lab

Joshua H. Lipschutz, M.D.Joshua Lipschutz, M.D.

Professor and Director
Division of Nephrology

The Lipschutz lab is focused on identifying the cellular and molecular mechanisms regulating renal cystogenesis and tubulogenesis. Understanding cystogenesis and tubulogenesis is critically important as 500,000 Americans have autosomal polycystic kidney disease (ADPKD), a disease of disordered ciliogenesis and cystogenesis that is the fourth leading cause of end-stage renal disease, and millions more suffer acute tubular necrosis (ATN), a leading cause of acute kidney injury (AKI), with AKI being both a strong independent predictor of mortality in hospitalized patients, and a risk factor for chronic kidney disease (CKD). Currently, there are no approved treatments for either ADPKD or AKI. In one of their most significant scientific accomplishments, the Lipschutz lab showed that when Exoc5, a central component of the highly-conserved eight-protein exocyst trafficking complex, was knocked down, ciliogenesis, cystogenesis, and tubulogenesis were all inhibited. When Exoc5 was overexpressed, these processes were enhanced. It was also shown that the exocyst was necessary for ciliogenesis due to its role in trafficking intracellular vesicles containing ciliary proteins, such as polycystin-2 (the protein product of one of the two genes, which when mutated, cause ADPKD). Dr. Lipschutz and laboratory members then showed that the small GTPase Cdc42 was necessary for ciliogenesis and acted to localize and regulate the exocyst at the primary cilium in vitro in cell culture, and in vivo in zebrafish and mice.

Since moving from Pennsylvania to MUSC on July 1, 2014, the Lipschutz Lab and his collaborators have continued their pioneering ciliogenesis/PKD work with the generation and characterization of an Exoc5 fl/fl mouse that allowed for kidney-specific knockout of Exoc5 fl/fl mouse that allowed for kidney-specific knockout of Exoc5, the demonstration that the exocyst critically interacts with Arl13b during ciliogenesis, and the discovery that Tuba regulates Cdc42, which, in turn, regulates the exocyst. The lab has also ventured outside of the kidney to show that the role of the exocyst in retinal ciliogenesis is conserved across organs and species. 

Publications:

Pubmed Collection