Dr. Wiggins' laboratory is focused on the glomerular podocyte, the major cell responsible for maintaining the filtration barrier of the glomerulus. Recent unpublished work has been on the question of podocyte numbers in the glomerulus because accumulating experimental and clinical evidence from the Wiggins laboratory and other laboratories suggests that podocyte depletion may be the single most important factor driving progression of glomerular diseases. Experimental systems that have been used include the PAN model in the rat and a new model developed in the Wiggins lab where the human diphtheria toxin (DT) receptor transgene (under the control of a podocin promoter that the Holzman/Wiggins group has shown to be specific for podocytes) has been expressed on rat podocytes so that DT can be used to specifically deplete rats of podocytes in a predetermined and graded way. This work has also been extended to aging in the kidney because ESRD occurs predominantly in older people (average age of onset of dialysis at 65 years) using DNA microarray and similar approaches to show that podocyte stress and depletion may be a significant factor predisposing to ESRD in older people. Joint projects with Dr. Friedhelm Hildebrandt in Pediatric Nephrology at UM are focused on identifying mutations in genes responsible for steroid-responsive and steroid-resistant forms of nephrotic syndrome using positional cloning approaches in children and adults.
Link to PubMed Citations
Wiggins, JE, Goyal M, Wharram B and Wiggins R. The anti-oxidant Ceruloplasmin is expressed by glomerular parietal epithelial cells and secreted into the urine in association with glomerular aging and high calorie diet. J Am Soc Nephrol E-pub 2006.
Wiggins J, Goyal M, Sanden S, Wharram B, Shedden K, Misek D, Kuick R, Wiggins R. Podocyte hypertrophy, “adaptation” and “decompensation” associated with glomerular enlargement and glomerulosclerosis in the aging rat: Prevention by calorie restriction. J Am Soc Nephrol 16:2953-2966, 2005.
Wharram B, Goyal M, Wiggins J, Sanden S, Hussain S, Filipiak W, Saunders T, Dysko R, Kohno K, Holzman L, Wiggins R. Podocyte depletion causes glomerulosclerosis. Diphtheria toxin-induced podocyte depletion in rats expressing the human DTR transgene. J Am Soc Nephrol 16:2941-2952, 2005.
Schultheiss M, Ruf RG, Mucha BE, Wiggins R, Fuchshuber A, Lichtenberger A, Hildebrandt F. No evidence for genotype/phenotype correlation in NPHS1 and NPHS2 mutations. Pediatr Nephrol. 19:1340-8, 2004.
Moeller MJ, Soofi A, Hartmann I, Le Hir M, Wiggins R, Kriz W, Holzman LB. Podocytes populate cellular crescents in a murine model of inflammatory glomerulonephritis. J Am Soc Nephrol. 15:61-7. 2004.
Weitzel WF, Kim K, Rubin JM, Wiggins RC, Xie H, Chen X, Emelianov SY, O'Donnell M. Feasibility of applying ultrasound strain imaging to detect renal transplant chronic allograft rejection. Kidney Int. 65:733-736, 2004.
Moeller MJ, Sanden SK, Soofi A, Wiggins RC, Holzman LB. Podocyte-specific expression of Cre recombinase in transgenic mice. Genesis 55:39-42, 2003.
Verma R, Wharram B, Kovari I, Kunkel R, Nihalini D, Way KK, Wiggins RC, Killen P, Holzman LB. Fyn binds to and phosphorylates the kidney slit diaphragm component nephrin. J Biol Chem 278:20716-20723, 2003.
Sanden SK, Wiggins JE, Goyal M, Riggs LK, Wiggins RC. Evaluation of a thick and thin section method for estimation of podocyte number, glomerular volume and glomerular volume per podocyte (GV/P) in rat kidney using WT-1 as a podocyte nuclear marker. J Am Soc Nephrol 14:2484-2493, 2003.
Okechukwu CN, Hulbert-Shearon T, Wolfe RA, Wiggins R, Port FK. Lack of correlation between facility-based standardized rates of transplantation and mortality. Am J Kidney Dis 40:381-384, 2002.
Moeller MJ, Sanden SK, Soofi A, Wiggins RC, Holzman LB. Two gene fragments that direct podocyte-specific expression in transgenic mice. J Am Soc Nephrol 13:1561-1567, 2002.
Roh MH, Makarova O, Liu CJ, Shin KY, Lee S, Laurinec S, Goyal M, Wiggins R, Margolis B. The Maguk protein, Pals1, functions as an adapter, linking mammalian homologues of crumbs and discs lost. J Cell Biol 157:161-172, 2002.
Kim YH, Goyal M, Wharram B, Wiggins J, Kershaw D, Wiggins R. Reduced expression of the podocyte GLEPP1 receptor tyrosine phosphatase (Ptpro) in rat PAN nephrosis. Nephron 90:471-476, 2002.
Wiggins R, Kershaw D, Smoyer W, Holzman L. The glomerular podocyte. In: Immunologic Renal Diseases. Neilson E, Couser W, eds, 2001.
Kim YH, Goyal M, Kurnit D, Wharram B, Wiggins J, Holzman L, Kershaw D, Wiggins R. Podocyte depletion and glomerulosclerosis have a direct relationship in the PAN-treated rat. Kidney Int 60:957-968, 2001.
Patrie KM, Dreschler AJ, Goyal M, Wiggins RC, Margolis B. The membrane-associated guanylate kinase protein MAGI-1 binds megalin and is present in glomerular podocytes. J Am Soc Nephrol 12:667-677, 2001.
Wiggins RC. The vascular adventitial cell (VAC) and its role in scarring in the kidney. In: Molecular Biology of the Kidney in Health and Disease. Schlondorff D, Bonventre JV, eds. Marcel, Dekker Inc., New York , 2000.
Wiggins RC, Kershaw DB. Crescentic glomerulonephritis and the clinical syndrome of rapidly progressive glomerulonephritis (RPGN). In: Textbook of Nephrology. Glassock RJ, ed., 2000.
Emelianov SY, Lubinski MA, Skovoroda AR, Erkamp RQ, Leavey SF, Wiggins RC, O’Donnell M. Reconstructive ultrasound elasticity imaging for renal transplant diagnosis: Kidney ex vivo results. Ultrasonic Imaging 22:178-194, 2000.
Wharram BL, Goyal M, Gillespie PJ, Wiggins JE, Kershaw DB, Holzman LB, Dysko RC, Saunders TL, Samuelson LC, Wiggins RC. Altered podocyte structure in GLEPP1 (Ptpro)-deficient mice associated with hypertension and low glomerular filtration rate. J Clin Invest 106:1281-1290, 2000.
Wang R., St.John PL , Kretzler M., Wiggins RC, Abrahamson DR . Molecular cloning, expression, and distribution of GLEPP1 in developing mouse kidney. Kidney Int 57:1847-1859, 2000.