Soundarapandian Vijayakumar
| Title | Assistant Professor |
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| Institution | School of Medicine and Dentistry |
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| Department | Pediatrics |
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| Address | University of Rochester Medical Center School of Medicine and Dentistry 601 Elmwood Ave, Box 777 Rochester NY 14642
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| Title | Assistant Professor |
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| Institution | School of Medicine and Dentistry |
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| Department | Pharmacology and Physiology |
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| 1987 |
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| 1995 | Travel Grants | International Society for the study of Origins of Life | | 2008 |
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| 2010 | Strong Childrens Research Center, University of Rochester, Rochester, NY. Role of galectin-3 in ARPKD | | 2010 |
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| 2011 | CTSI Lab Support Grant, Role of Galectin-3 Mediated Extracellular Matrix Assembly in ARPKD Cystogenesis | URMC CTSI |
My lab has two main areas of interests: 1. Identification of molecular mechanisms that cause cyst growth in ARPKD
ARPKD is a rare but severe hereditary disease associated with a high perinatal mortality. Using PCK rat that harbors a spontaneous splicing mutation in the PKHD1 gene and exhibits many characteristics of human ARPKD as our model system, we are investigating the molecular mechanisms that regulate ARPKD cystogenesis. In particular we are interested in identifying novel proteins that interact with fibrocystin and identifying novel therapeutic agents that could inhibit cyst growth. We utilize microarray, real-time PCR, confocal microscopy, flow sorting and organ culture techniques in addition to standard biochemical and cell biological tools.
2. Mechanisms that regulate kidney intercalated cell differentiation and adaptation
Metabolic acidosis is a clinical disturbance characterized by an increase in blood plasma acidity and can lead to major cardiovascular, respiratory and skeletal abnormalities. Normal kidneys respond to metabolic acidosis by reversing their proton pumping activity and bicarbonate flux with the help of A-type and B-type intercalated cells of the kidney. We discovered that a novel 230kD extracellular matrix protein, hensin mediates this regulation by remodeling the intercalated cells. Hensin is a multifunctional protein and its orthologs DMBT1 and Gp-340 have been implicated in tumor suppression and innate immunity respectively. We are currently investigating (A) the role of galectin-3 in ECM assembly of hensin (B) the role of peptidyl prolyl isomerases in hensin folding and (C) signaling mechanisms regulated by hensin that lead to epithelial remodeling. We are using cell culture and knock-out mice models in these studies. The long term objective is to identify mechanisms that lead to differentiation of intercalated cells. An active collaboration with Schwartz Lab is ongoing.
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Peng H, Vijayakumar S, Schiene-Fischer C, Li H, Purkerson JM, Malesevic M, Liebscher J, Al-Awqati Q, Schwartz GJ. Secreted cyclophilin A, a peptidylprolyl cis-trans isomerase, mediates matrix assembly of hensin, a protein implicated in epithelial differentiation. J Biol Chem. 2009 Mar 6; 284(10):6465-75.
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Vijayakumar S, Erdjument-Bromage H, Tempst P, Al-Awqati Q. Role of integrins in the assembly and function of hensin in intercalated cells. J Am Soc Nephrol. 2008 Jun; 19(6):1079-91.
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Vijayakumar S, Takito J, Gao X, Schwartz GJ, Al-Awqati Q. Differentiation of columnar epithelia: the hensin pathway. J Cell Sci. 2006 Dec 1; 119(Pt 23):4797-801.
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Schwaderer AL, Vijayakumar S, Al-Awqati Q, Schwartz GJ. Galectin-3 expression is induced in renal beta-intercalated cells during metabolic acidosis. Am J Physiol Renal Physiol. 2006 Jan; 290(1):F148-58.
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Watanabe S, Tsuruoka S, Vijayakumar S, Fischer G, Zhang Y, Fujimura A, Al-Awqati Q, Schwartz GJ. Cyclosporin A produces distal renal tubular acidosis by blocking peptidyl prolyl cis-trans isomerase activity of cyclophilin. Am J Physiol Renal Physiol. 2005 Jan; 288(1):F40-7.
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Al-Awqati Q, Vijayakumar S, Takito J. Terminal differentiation of epithelia from trophectoderm to the intercalated cell: the role of hensin. J Am Soc Nephrol. 2003 Jun; 14 Suppl 1:S16-21.
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Genter MB, Burman DM, Vijayakumar S, Ebert CL, Aronow BJ. Genomic analysis of alachlor-induced oncogenesis in rat olfactory mucosa. Physiol Genomics. 2002 Dec 26; 12(1):35-45.
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Schwartz GJ, Tsuruoka S, Vijayakumar S, Petrovic S, Mian A, Al-Awqati Q. Acid incubation reverses the polarity of intercalated cell transporters, an effect mediated by hensin. J Clin Invest. 2002 Jan; 109(1):89-99.
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Ma JF, Takito J, Vijayakumar S, Peehl DM, Olsson CA, Al-Awqati Q. Prostatic expression of hensin, a protein implicated in epithelial terminal differentiation. Prostate. 2001 Sep 15; 49(1):9-18.
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Hikita C, Vijayakumar S, Takito J, Erdjument-Bromage H, Tempst P, Al-Awqati Q. Induction of terminal differentiation in epithelial cells requires polymerization of hensin by galectin 3. J Cell Biol. 2000 Dec 11; 151(6):1235-46.
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Schwartz GJ, Kittelberger AM, Barnhart DA, Vijayakumar S. Carbonic anhydrase IV is expressed in H(+)-secreting cells of rabbit kidney. Am J Physiol Renal Physiol. 2000 Jun; 278(6):F894-904.
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Al-Awqati Q, Vijayakumar S, Takito J, Hikita C, Yan L, Wiederholt T. Terminal differentiation in epithelia: the Hensin pathway in intercalated cells. Semin Nephrol. 1999 Sep; 19(5):415-20.
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Takito J, Yan L, Ma J, Hikita C, Vijayakumar S, Warburton D, Al-Awqati Q. Hensin, the polarity reversal protein, is encoded by DMBT1, a gene frequently deleted in malignant gliomas. Am J Physiol. 1999 Aug; 277(2 Pt 2):F277-89.
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Hikita C, Takito J, Vijayakumar S, Al-Awqati Q. Only multimeric hensin located in the extracellular matrix can induce apical endocytosis and reverse the polarity of intercalated cells. J Biol Chem. 1999 Jun 18; 274(25):17671-6.
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Vijayakumar S, Takito J, Hikita C, Al-Awqati Q. Hensin remodels the apical cytoskeleton and induces columnarization of intercalated epithelial cells: processes that resemble terminal differentiation. J Cell Biol. 1999 Mar 8; 144(5):1057-67.
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Al-Awqati Q, Vijayakumar S, Hikita C, Chen J, Takito J. Phenotypic plasticity in the intercalated cell: the hensin pathway. Am J Physiol. 1998 Aug; 275(2 Pt 2):F183-90.
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Wigley WC, Vijayakumar S, Jones JD, Slaughter C, Thomas PJ. Transmembrane domain of cystic fibrosis transmembrane conductance regulator: design, characterization, and secondary structure of synthetic peptides m1-m6. Biochemistry. 1998 Jan 20; 37(3):844-53.
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Chen J, Vijayakumar S, Li X, Al-Awqati Q. Kanadaptin is a protein that interacts with the kidney but not the erythroid form of band 3. J Biol Chem. 1998 Jan 9; 273(2):1038-43.
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van't Hof W, Malik A, Vijayakumar S, Qiao J, van Adelsberg J, Al-Awqati Q. The effect of apical and basolateral lipids on the function of the band 3 anion exchange protein. J Cell Biol. 1997 Nov 17; 139(4):941-9.
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Vijayakumar S, Salerno JC. Molecular modeling of the 3-D structure of cytochrome P-450scc. Biochim Biophys Acta. 1992 Dec 28; 1160(3):281-6.
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