Joshua Henry Lipschutz

faculty photo
Adjunct Associate Professor of Medicine
Department: Medicine

Contact information
Medical University of South Carolina
96 Jonathan Lucas Street
MSC 629
Charleston, SC 29425
Education:
B.A. (Chemistry)
Indiana University, 1984.
M.D. (Medicine)
Indiana University School of Medicine, 1988.
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Description of Research Expertise

Research Interests:
The Lipschutz Lab is interested in kidney development, especially as it relates to recovery from injury and cystic kidney disease.

Keywords: Ciliogenesis, Cystogenesis, Tubulogenesis, and Kidney Development

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Research Details:

Cystogenesis and tubulogenesis are important for many complex biological processes such as organ development, regeneration following acute kidney injury (AKI), and diseases such as Autosomal Dominant Polycystic Kidney Disease (ADPKD). This lab has three basic experimental goals: first, to find novel genes involved in cyst and tubule formation using techniques such as DNA microarray analysis; second, to determine the molecular mechanism by which these candidate genes act using both in vitro and in vivo studies, such as the creation of transgenic and knockout mice, and knockdown and overexpression of proteins in zebrafish; and, finally, to utilize this knowledge to identify treatment strategies for ADPKD and to accelerate recovery following AKI.



An example of a group of candidates genes for cyst and tubule formation, identified by the Lipschutz Lab, is the exocyst complex. The exocyst is a highly conserved eight protein complex involved in the biogenesis of polarity in organisms as diverse as yeast and mammals. The exocyst is centrally involved in cystogenesis/tubulogenesis and acts by specifically modulated synthesis and delivery of basolateral plasma membrane and secretory proteins. One member of the exocyst complex, Sec10, is particularly important in that it acts as a bridge between the vesicles that carry polarized proteins and the rest of the exocyst complex, which is found adjacent to the plasma membrane. Current studies are investigating how the exocyst acts at a cellular and molecular level and the role of exocyst complex in kidney development. Given the relatively ubiquitous expression of the exocyst complex in a variety of different cells and organs, the Cre-Lox system has been used to generate mice with a kidney-specific disruption in the Sec10 gene.

Many diseases, such as ADPKD, involve reactivation of developmental programs. ADPKD is the most common potentially lethal monogenic disorder and affects 500,000 Americans alone. In the case of ADPKD, gigantic cystic structures form that ultimately result in the destruction of the kidney. Defects in ciliogenesis are central to the pathogenesis of ADPKD, and the Lipschutz Lab has shown that the exocyst is necessary for ciliogenesis and that the exocyst traffics polycystin-2 in vitro and in vivo. Polycystin-2 is the protein product of PKD2, one of two genes, which when mutated, cause ADPKD. Abnormalities in the exocyst complex have been demonstrated in tissue samples and cell lines derived from patients with ADPKD by this lab and others. In both yeast and mammals, the exocyst is controlled by the Rho family of small GTP-binding proteins. We have recently shown that Rho family proteins interact with the exocyst to regulate cyst and tubule formation, as well as ciliogenesis. The Lipschutz Lab also showed that the exocyst protects renal tubule cells from injury both in vitro and in vivo by activating the MAPK pathway. Using mouse models of ADPKD and AKI, the Lipschutz Lab, in collaboration with the Bennett Lab at Penn, is using AAV-mediated gene therapy to treat both ADPKD and AKI.

Description of Itmat Expertise

Dr. Lipschutz's research interest is in autosomal dominant polycystic kidney disease (ADPKD), acute kidney injury (AKI), and kidney development.

Selected Publications

Fogelgren B, Polgar N, Lui VH, Lee AJ, Tamashiro KK, Napoli JA, Walton CB, Zuo X, Lipschutz JH: Urothelial Defects from Targeted Inactivation of Exocyst Sec10 in Mice Cause Ureteropelvic Junction Obstructions. PloS One 5(10): e0129346, 2016.

Seixas C, Choi SY, Polgar N, Umberger NL, East MP, Zuo X, Moreiras H, Ghossoub R, Benmerah A, Kahn RA, Fogelgren B, Caspary T, Lipschutz JH, Barral DC: Arl13b and the exocyst interact synergistically in ciliogenesis. Molecular Biology of the Cell 27(2): 308-320, 2016.

Kwon SH, Oh S, Nacke M, Mostov K, Lipschutz JH: CD2AP and LMAN2 regulate exosome cargo protein trafficking through the Golgi network. Journal of Biological Chemistry 2016 Notes: Epub ahead of print.

Han SJ, Jang HS, Kim JI, Lipschutz JH, Park KM: Unilateral nephrectomy elongates primary cilia in the remaining kidney via reactive oxygen species. Scientific Reports Page: 22281, 2016.

Baek JI, Kwon SH, Zuo X, Choi SY, Kim SH, Lipschutz JH : Dynamin binding protein (Tuba) deficiency inhibits ciliogenesis and nephrogenesis in vitro and in vivo. Journal of Biological Chemistry 291(16): 8632-8643, 2016.

Cdc42 and Sec10 are Required for Normal Retinal Development in Zebrafish: Choi SY, Baek JI, Zuo X, Kim SH, Dunaief JL, Lipschutz JH. Investigative Ophthalmology and Visual Science 56(5): 3361-3370, 2015.

Kim SH, Baek JI, Wu S, Choi SY, Su Y, Flynn CR, Gamse JT, Ess KC, Hardiman GT, Lipschutz JH, Rockey D : A Post-developmental Genetic Screen for Zebrafish models of Inherited Liver Disease. PLoS One 10(5): e0125980, 2015.

Huang L, Choi SY, Chacon-Heszele MF, Zhou W, Ryu YK, McKenna S, Zuo X, Kuruvilla R, Lipschutz JH: Wnt5a is Necessary for Kidney Development in Zebrafish and Mice. Nephron Experimental Nephrology 128(1-2): 80-88, 2014.

Chacon-Heszele MF, Zuo X, Hellman NE, McKenna S, Choi SY, Huang L, Tobias JW, Park KM, Lipscutz JH: Novel MAPK-dependent and independent tubulogenesis genes identified via microarray analysis. American Journal of Physiology, Renal Physiology 306: F1047-F1058, 2014.

Choi SY, Baek JI, Zuo X, Kim SH, Dunaief JL, Lipschutz JH: Cdc42 and Sec10 are Required for Normal Retinal Development in Zebrafish. Investigative Ophthalmology and Visual Science 56(5): 3361-3370, 2014.

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Last updated: 10/31/2016
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