James B. Wade
655 West Baltimore St.
Ph.D - Princeton University (1972)
Research in my laboratory is oriented toward understanding the cellular and molecular mechanisms involved in the signals mediating hormonal regulation of transport by kidney epithelial cells. Hormonal regulation of epithelial transport is essential for appropriate control of the volume and composition of body fluids. Antidiuretic hormone (ADH) and aldosterone play a central role in this control by regulating sodium and water transport by certain epithelial cells in the kidney. ADH increases the water permeability of responsive epithelia by causing vesicles containing water channels to fuse with the cell's apical membrane. ADH also regulates concentrating ability by regulating a family of urea transporters. Aldosterone regulates the amount of the epithelial Na channel ENaC, the NaCl cotransporter, NCC and the K channel, ROMK in the apical membrane. We have been studying the role of membrane vesicle traffic in these responses using specific antibodies to immunolocalize transporters and PDZ proteins involved in the targeting and regulation of membrane transporters. We are also interested in signaling via serine/threonine kinases WNK1 especially WNK1 and WNK4 which are involved in regulating blood pressure and K balance.
Lab Techniques and Equipment:
- Confocal Microscopy
- Frozen and Ultrathin Sectioning
- Electron Microscopy
- Western immunoblots
- oocyte expression studies
Shenolikar S, Voltz JW, Minkoff CM, Wade JB and Weinman EJ. (2002) Targeted disruption of the mouse NHERF-1 gene promotes internalization of proximal tubule sodium-phosphate cotransporter type IIa and renal phosphate wasting. Proc Natl Acad Sci U. S A. 99:11470-5.
Wade JB, Liu J, Coleman RA, Cunningham R, Steplock DA, Lee-Kwon W, Pallone TL, Shenolikar S, Weinman EJ. (2003) Localization and interaction of NHERF isoforms in the renal proximal tubule of the mouse. Am J Physiol Cell Physiol. 285:C1494-C1503.
Weinman EJ, Boddeti A, Cunningham R, Akom M, Wang F, Wang Y, Liu J, Steplock D, Shenolikar S, Wade JB. (2003) NHERF-1 is Required for Renal Adaptation to a Low Phosphate Diet. Am J Physiol Renal Physiol. 285:F1225-F1232.
Spector DA, Yang Q, Liu J, Wade JB. (2004 Jul) Expression, localization, and regulation of urea transporter B in rat urothelia. Am J Physiol Renal Physiol. 287(1):F102-108.
Olsen O, Wade JB, Morin N, Bredt DS, Welling PA. (2005) Differential localization of the Mammalian Lin 7 (MALS/Veli) PDZ Proteins in the Kidney. Am J Physiol Renal Physiol.; 288: F345-F352.
Khan O, Riazi S, Hu X, Song J, Wade JB, and Ecelbarger CA. (2005) Regulation of the Renal Thiazide-Sensitive Na-Cl Cotransporter, Blood Pressure, and Natriuresis in Obese Zucker Rats Treated with Rosiglitazone. Am J Physiol Renal Physiol 289(2):F442-50.
Coleman RA, Liu J, Wade JB. (2006) Use of Anti-fluorophore Antibody to Achieve High-Sensitivity Immunolocalizations of Transporters and Ion Channels. J Histochem Cytochem. 54(7):817-27.
Wade JB, Fang L, Liu J, Li D, Yang C-L, Subramanya AR, Maouyo D, Mason A, Ellison DH, and Welling PA. (2006) WNK1 Kinase Isoform Switch Regulates Renal Potassium Excretion. Proc. Natl. Acad. Sci. U.S.A. 103(22):8558-63.
Cunningham R, Esmaili A, Brown E, Biswas RS, Murtazina R, Donowitz M, Dijkman HB, van der Vlag J, Hogema BM, De Jonge HR, Shenolikar S, Wade JB, Weinman EJ. (2008) Urine electrolyte, mineral, and protein excretion in NHERF-2 and NHERF-1 null mice. Am J Physiol Renal Physiol. 294(4):F1001-7. PMID:18256311
Tiwari S, Sharma N, Gill PS, Igarashi P, Kahn CR, Wade JB, Ecelbarger CM. (2008) Impaired sodium excretion and increased blood pressure in mice with targeted deletion of renal epithelial insulin receptor. Proc Natl Acad Sci U S A. Apr 18 105(17):6469-74. PMCID: PMC2359822
Spector DA, Yang Q, Klopouh L, Deng J, Weinman EJ, Steplock DA, Biswas R, Brazie MF, Liu J, Wade JB. (2008) The ROMK potassium channel is present in mammalian urinary tract epithelia and muscle. Am J Physiol Renal Physiol. Dec;295(6):F1658-65. PMCID: PMC2604824
Wang Y, O'Connell JR, McArdle PF, Wade JB, Dorff SE, Shah SJ, Shi X, Pan L, Rampersaud E, Shen H, Kim JD, Subramanya AR, Steinle NI, Parsa A, Ober CC, Welling PA, Chakravarti A, Weder AB, Cooper RS, Mitchell BD, Shuldiner AR, Chang YP. (2009) Whole-genome association study identifies STK39 as a hypertension susceptibility gene. Proc Natl Acad Sci U S A. Jan 6;106(1):226-31. 2009 PMCID: PMC2629209
Subramanya AR, Liu J, Ellison DH, Wade JB, Welling PA. (2009) WNK4 diverts the thiazide-sensitive NaCl cotransporter to the lysosome and stimulates AP-3 interaction. J Biol Chem. 284:18471-18480. 2009 PMCID: PMC2709348
Fang L, Bo-Young Kim, Wade JB, Welling PA. (2009) The ARH Adaptor Protein Targets the Kidney ROMK Potassium Secretory Channel for Endocytosis. J Clinical Invest. Nov;119(11):3278-89. PMCID: PMC2769171
Wade JB, Fang L, Coleman RA, Liu J, Grimm PR, Wang T, Welling PA. (2011) Differential Regulation of ROMK (Kir1.1) in Distal Nephron Segments by Dietary Potassium. Am J Physiol Renal Physiol. 300(6):F1385-93. PMCID: PMC3119145
Liu W, Schreck C, Coleman RA, Wade JB, Hernandez Y, Zavilowitz B, Warth R, Kleyman TR, Satlin LM. (2011) Role of NKCC in BK channel-mediated net K+ secretion in the CCD. Am J Physiol Renal Physiol. 301(5):F1088-97 PMCID: PMC3280697
Grimm PR, Taneja TK, Liu J, Coleman R, Chen YY, Delpire E, Wade JB, Welling PA. (2012) SPAK isoforms and OSR1 regulate sodium-chloride co-transporters in a nephron-specific manner. J Biol Chem. Nov 2;287(45):37673-90 PMCID: PMC3488044
Li L, Garikepati RM, Tsukerman S, Kohan D, Wade JB, Tiwari S, Ecelbarger CM. (2013) Reduced ENaC activity and blood pressure in mice with genetic knockout of the insulin receptor in the renal collecting duct. Am J Physiol Renal Physiol. Feb;304(3):F279-88. PMCID: PMC3566522