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

Chacon-Heszele MF, Zuo X, Hellman NE, McKenna S, Choi SY, Huang L, Tobias JW, Park KM, Lipschutz JH: Novel MAPK-dependent and -independent tubulogenes identified via microarray analysis of 3D-cultured Madin-Darby canine kidney cells. Am J Physiology Renal Physiology 306(9): F1047-58, 2014.

Baek JI, Choi SY, Chacon-Heszele MF, Zuo X, Lipschutz JH: Expression of Drosophila forkhead transcription factors during kidney development. Biochemical and Biophysical Research Communications 446(1): 15-17, 2014.

Choi SY, Chacon-Heszele MF, Huang, L, McKenna, S, Wilson, FP, Zuo, X, Lipschutz, JH : Cdc42 deficiency causes ciliary abnormalities and cystic kidneys. Journal of the American Society of Nephrology 24(9): 1435-1450, 2013.

Jang HA, Han SJ, Kim JI, Lee S, Lipschutz JH, Park KM: Activation of ERK accelerates repair of renal tubular epithelial cells, whereas it inhibits progression of fibrosis following ischemia/reperfusion injury. Biochimica et Biophysica Acta-Molecular Basis of Disease 1832(12), 2013.

Kim JI, Kim J, Jang HS, Noh MR, Lipschutz JH, Park KM : Reduction of oxidative stress during recovery accelerates normalization of primary cilia length that is altered after ischemic injury in murine kidneys American Journal of Physiology, Renal Physiology 304(10), 2013.

Choi SY, Fogelgren B, Zuo X, Huang, L, McKenna S, Lingappa VR, Lipschutz JH: Exocyst Sec10 is involved in basolateral protein translation and translocation in the endoplasmic reticulum. Nephron Experimental Nephrology 120:e133-e139, Oct 2012.

Chung DC, Fogelgren B, Park KM, Heidenberg J, Zuo X, Huang L, Bennett J, Lipschutz JH: Adeno-associated virus (AAV)-mediated gene transfer to renal tubule cells via a retrograde ureteral approach Nephron Extra 1: 217-223, Nov 2011.

Zuo X, Fogelgren B, Lipschutz JH : The small GTPase Cdc42 is essential for primary ciliogenesis in renal tubular epithelial cells. Journal of Biological Chemistry 286(25): 22469-22477, Jun 2011.

Fogelgren B, Lin SY, Zuo X, Jaffe K, Park KM, Reichert RJ, Bell PD, Burdine RD, Lipschutz JH: The exocyst protein Sec10 interacts with polycystin-2 and knockdown causes PKD-phenotypes. PLoS Genetics 7(4): e1001361, Apr 2011.

Blosser C ,Gashu A, Wu S, Lomagro RM , Malone E, Brunelli SM, Itkin M, Golden , McCombs P, Lipschutz JH: High rate of fistula placement in a cohort of dialysis patients in a single payer system. Hemodialysis International 14(4): 393-7, Oct 2010.

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Last updated: 07/01/2014
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