Department of Internal Medicine

Nephrology Faculty

John Stokes photo

Medical School:
Temple University

Residency:
Washington University
University of Texas, Southwestern

Fellowship:
University of Texas, Southwestern

John B. Stokes, M.D.
Professor
Director, Division of Nephrology

Dr. Stokes' research addresses the mechanisms whereby ions are translocated across cell membranes and how these processes are regulated. Most recently he has focused on understanding how Na is translocated across the Epithelial Na Channel, (ENaC). This ion channel is composed of three different subunits (alpha, beta, and gamma). Steroid hormones as well as several peptide hormones regulate this ion channel. Mutations of two of these subunits can produce activation of the channel and are responsible for the syndrome of hypertension and hypokalemia called Liddle Syndrome. The regulation of this ion channel is of critical importance in blood pressure regulation and Na and K homeostasis. The molecular interactions responsible for this regulation are being unraveled and structural proteins and kinases responsible for proper functioning of the channel are being studied. Methods used in Dr. Stokes' laboratory to study this channel include electrophysiology of model epithelial monolayers, heterologous expression in Xenopus oocytes, overexpression of proteins using adenovirus, structural alteration with functional analysis, immunofluorescence, genetic engineering and targeting, and biochemical analyses of second messengers. Dr. Stokes is the Director of the NIH supported O'Brien Kidney Research Center at the University of Iowa. This Center is investigating some aspects of ENaC regulation.

Dr Stokes also coordinates the University of Iowa site of a clinical trial on Nocturnal Dialysis, a NIH-sponsored study examining the effects of intensive dialysis on patients with End Stage Renal Disease. This study is designed to evaluate effects on hospitalization, quality of life, and cardiovascular complications in patients on dialysis.

Honors, Awards, and Organizations

Recent Publications

  1. Cao, X., Shi, P., Sigmund, R., Husted, R., Sigmund, C.D., Williamson, R., Stokes, J.B., and Yang, B.,: Mice Heterozygous for Beta-ENaC Deletion have Defective Potassium Excretion. Am. J. Physiol. Renal, (In Press), 2006.
  2. Olakanmi, O., Stokes, J., and Britigan, B.E.: Gallium-Inducible Transferrin-Independent Iron Acquisition is a Property of Many Cell Types: Possible Role of Alterations in the Plasma Membrane. J. Invest. Med., 53(3):143-153, 2005.
  3. Uc, A., Husted, R.F., Giriyappa, R.L., Britigan, B.E., and Stokes, J.B.: Hemin Induces Active Chloride Secretion in Caco-2 Cells. Am. J. Physiol. Gastrointest. Liver Physiol., 289:G202-G208, 2005.
  4. Itani, O., Stokes, J.B., and Thomas, C.P.: Nedd4-2 Isoforms Differentially Associate with ENaC and Regulate Its Activity. Am. J. Physiol. Renal Physiol., 298:F334-F346, 2005.
  5. Volk, K.A., Husted, R.F., Sigmund, R.D., and Stokes, J.B.: Overexpression of the Epithelial Na + Channel ? Subunit in Collecting Duct Cells. J. Biol. Chem. 280:18348-18354, 2005.
  6. Fernández-Llama, P., Ageloff, S., Fernández-Varo, G., Ros, J., Wang, X., Garra, N., Esteva-Font, C., Ballarin, J., Barcelo, P., Arroyo, V., Stokes, J.B., Knepper, M.A., and Jiménez, W.: Sodium Retention in Cirrhotic Rats is Associated with Increased Renal Abundance of Sodium Transporter Proteins. Kidney Int., 67:622-630, 2005.
  7. Uc, A., Stokes, J.B., and Britigan, B.E.: Heme Transport Exhibits Polarity in Caco-2 Cells: Evidence for an Active and Membrane Protein-Mediated Process. Am. J. Physiol. Gastrointest. Liver Physiol., 287:G1150-G1157, 2004.
  8. Naray-Fejes-Toth, A., Helms, M.N., Stokes, J.B., and Fejes-Toth, G. Regulation of sodium transport in mammalian collecting duct cells by aldosterone-induced kinase. SGK1: structure/function studies. Molecular and Cellular Endcrinology, 217:197-202, 2004.
  9. Fenton, R.A., Chou, C.-L., Ageloff, S., Brandt, W., Stokes, J.B., and Knepper, M.A.:  Increased Collecting Duct Urea Transporter Expression in Dahl Salt-Sensitive Rats.  Am. J. Physiol. (Renal Physiol.), 285:F143-F151, 2003.
  10. Masilamani, S., Wang, X., Kim, G.-H., Nielsen, S., Nakamura, K., Stokes, J.B., and Knepper, M.A.:  Time Course of Changes in Renal NHE3, NKCC2, NCC, Na-K-ATPase and ENaC Expression with Dietary NaCl Restriction.  Am. J. Physiol. (Renal Physiol.), 283 :F648-F657, 2002.
  11. Olakanmi, O., Rasmussen, G.T., Lewis, T.S., Stokes, J.B., Kemp, J.D., and Britigan, B.E.:  Multi-valent Metal Induced Iron Acquisition from Transferrin and Lactoferrin by Myeloid Cells.  J. Immunol., 169 :2076-2084, 2002.
  12. Nakamura, K., Stokes, J.B., and McCray, Jr., P.B.:  Endogenous and Exogenous Glucocorticoid Regulation of ENaC mRNA Expression in Developing Kidney and Lung.  Am. J. Physiol. (Cell), 283 :C762-C772, 2002.
  13. Itani, O.A., Auerbach, S.D., Husted, R.F., Volk, K.A., Ageloff, S., Knepper, M.A., Stokes, J.B., and Thomas, C.P.:  Glucocorticoid-stimulated lung epithelial Na+ transport is associated with regulated ENaC and sgk1 expression.  Am. J. Physiol. Lung Cell. Mol. Physiol., 282 :L631-L641, 2002.
  14. Volk, K.A., Snyder, P.M., and Stokes, J.B.:  Regulation of epithelial Na channel activity through a region of the carboxy terminus of the alpha subunit.  Evidence for intracellular kinase mediated reactions.  J. Biol. Chem., 276 :43887-43893, 2001.
  15. Náray-Fejes-Tóth, A., Fejes-Tóth, G., Volk, K.A., Stokes, J.B.: SGK is a Primary Glucocorticoid-induced Gene in the Human. J. Steroid Biochem. Mol. Biol., 75 : 51-56, 2000.
  16. Husted, R.F., Sigmund, R.D., and Stokes, J.B.: Mechanisms of Inactivation of the Action of Aldosterone on Collecting Duct by TGF- b. Am. J. Physiol., (Renal Physiol.), 278 : F425-F433, 2000.
  17. Volk, K.A., Husted, R.F., Snyder, P.M., and Stokes, J.B.: Kinase Regulation of hENaC Mediated through a Region in the COOH-terminal Portion of the a Subunit. Am. J. Physiol., (Cell Physiol.), 278 : C1047-C1054, 2000.
  18. Stokes, J.B.: Physiologic Resistance to the Action of Aldosterone. Kidney Int., 57 : 1319 - 1323, 2000.
  19. Thomas, C.P., Auerbach, S.D., Stokes, J.B., and Volk, K.A.: 5' Heterogeneity in Epithelial Sodium Channel a -subunit mRNA Leads to Distinct NH2-terminal Variant Proteins. Am. J. Physiol., 274 (Cell Physiol. 43):C1312-C1323, 1998.
  20. Stokes, J.B. and Sigmund R.D.: Regulation of rENaC mRNA by Dietary NaCl and Steroids: Organ, Tissue, and Steroid Heterogeneity. Am. J. Physiol., 274 (Cell Physiol. 43):C1699-C1707, 1998.
  21. Goulet, C.C., Volk, K.A., Adams, C.M., Prince, L.S., Stokes, J.B., and Snyder, P.M.: Inhibition of the Epithelial Na + Channel by Interaction of Nedd4 with a PY Motif Deleted in Liddle's Syndrome. J. Biol. Chem., 273 (45):30012-30017, 1998.
  22. Sandra, A., Boes, M., Dake, B.L., Stokes, J.B., and Bar, R.S. Infused IGF-I/IGFBP-3 Complex Causes Glomerular Localization of IGF-I in the Rat Kidney. Am. J. Physiol., 275 (Endocrinology and Metabolism 38):E32-E37, 1998.
  23. Watanabe, S., Matsushita, K., Stokes, J.B., and McCray, P.B.: Developmental Regulation of Epithelial Sodium Channel Subunit mRNA Expression in Rat Colon and Lung. Am. J. Physiol., 275 (Gastrointestinal Liver Physiol. 38):G1227-G1235, 1998.
  24. Husted, R.F., Zhang, C., and Stokes, J.B.: Concerted Actions of IL-1 b Inhibit Na + Absorption and Stimulate Anion Secretion by IMCD Cells. Am. J. Physiol., 275 (Renal Physiol. 44):F946-F954, 1998.
  25. Kopp, U.C., Matsushita, K., Sigmund, R.D., Smith, L.A., Watanabe, S., and Stokes, J.B.: Amiloride-sensitive Na + Channels in Pelvic Uroepithelium Involved in Renal Sensory Receptor Activation. Am. J. Physiol., 275 (Regulatory Integrative Comp. Physiol. 44):R1780-R1792, 1998.
  26. Watanabe, S., Matsushita, K., McCray, P.B., and Stokes, J.B.: Developmental Expression of the Epithelial Na+ Channel in Kidney and Uroepithelia. Am. J. Physiol., 276 (Renal Physiol. 45):F304-314, 1999.
  27. McDonald, F.J., Yang, B., Hrstka, R.F., Drummond, H.A., Tarr, D.E., McCray, P.B., Stokes, J.B., Welsh, M.J., and Williamson, R.A.: Disruption of the b Subunit of the Epithelial Na + Channel in Mice: Hyperkalemia and Neonatal Death Associated with a Pseudohypoaldosteronism Phenotype. Proc. Natl. Acad. Sci., 96 :1727-1731, 1999.

Links of Interest

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