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
Executive Vice Chair for the Department of Internal Medicine
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. In addition to mineralocorticoid hormones, long-term regulation of this channel is influenced by such agents as transforming growth factor- and oxygen supply. Understanding how these factors can influence ion channels may have relevance for cardiovascular disease and cancer. His laboratory is also studying TRPM6, one of two known proteins that is both an ion channel and a kinase. Genetic defects in this molecule cause the syndrome hypomagnesemia with secondary hypocalcemia (HSH).  Methods used in Dr. Stokes' laboratory 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 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. He also directs an ancillary study to this trial investigating the effects of intensive dialysis on cognitive function.

Honors, Awards, and Organizations

Recent Publications

  1. Holstein SA, Stokes JB and Hohl RJ. Renal failure and recovery associated with second-generation Bcr-Abl kinase inhibitors in imatinib-resistant chronic myelogenous leukemia. Leuk Res 33: 344-347, 2009.
  2. Stokes JB, Berns AS, Henrich WL, McKinney TD, Molitoris BA and Palmer BF. Managing conflicts of interest: the road ahead. J Am Soc Nephrol 20: 1860-1862, 2009.
    Stokes JB, Haupt A, Molitoris BA, Kokemueller P and Ibrahim T. ASN policy on managing conflicts of interest. J Am Soc Nephrol 20: 1853-1859, 2009.
  3. Walder RY, Yang B, Stokes JB, Kirby PA, Cao X, Shi P, Searby CC, Husted RF and Sheffield VC. Mice defective in Trpm6 show embryonic mortality and neural tube defects. Hum Mol Genet 2009.
  4. Shi PP, Cao XR, Sweezer EM, Kinney TS, Williams NR, Husted RF, Nair R, Weiss RM, Williamson RA, Sigmund CD, Snyder PM, Staub O, Stokes JB and Yang B. Salt-sensitive hypertension and cardiac hypertrophy in mice deficient in the ubiquitin ligase Nedd4-2. Am J Physiol Renal Physiol 295: F462-F470, 2008.
  5. Husted RF, Volk KA, Sigmund RD and Stokes JB. Discordant effects of corticosteroids and expression of subunits on ENaC activity. Am J Physiol Renal Physiol 293: F813-F820, 2007.
  6. Shi PP, Cao XR, Qu J, Volk KA, Kirby P, Williamson RA, Stokes JB and Yang B. Nephrogenic diabetes insipidus in mice caused by deleting COOH-terminal tail of aquaporin-2. Am J Physiol Renal Physiol 292: F1334-F1344, 2007.
  7. Uc A, Reszka KJ, Buettner GR and Stokes JB. Tin Protoporphyrin Induces Intestinal Chloride Secretion By Inducing Light-Oxidation Processes. Am J Physiol Cell Physiol 292: C1906-C1914, 2007.
  8. Cao XR, Shi PP, Sigmund RD, Husted RF, Sigmund CD, Williamson RA, Stokes JB and Yang B. Mice heterozygous for beta-ENaC deletion have defective potassium excretion. Am J Physiol Renal Physiol 291: F107-F115, 2006.
  9. Fernandez-Llama P, Ageloff S, Fernandez-Varo G, Ros J, Wang X, Garra N, Esteva-Font C, Ballarin J, Barcelo P, Arroyo V, Stokes JB, Knepper MA and Jimenez W. Sodium retention in cirrhotic rats is associated with increased renal abundance of sodium transporter proteins. Kidney Int 67: 622-630, 2005.
  10. Itani OA, Stokes JB and Thomas CP. Nedd4-2 isoforms differentially associate with ENaC and regulate its activity. Am J Physiol Renal Physiol 289: F334-F346, 2005.
  11. Olakanmi O, Stokes JB and Britigan BE. Gallium-inducible transferrin-independent iron acquisition is a property of many cell types: possible role of alterations in the plasma membrane. J Investig Med 53: 143-153, 2005.
  12. Uc A, Husted RF, Giriyappa RL, Britigan BE and Stokes JB. Hemin induces active chloride secretion in Caco-2 cells. Am J Physiol Gastrointest Liver Physiol 289: G202-G208, 2005.
  13. Volk KA, Husted RF, Sigmund RD and Stokes JB. Overexpression of the Epithelial Na+ Channel {gamma} Subunit in Collecting Duct Cells: Interactions of Liddle's Mutations and Steroids on expression and Function. Journal of Biological Chemistry 280: 18348-18354, 2005.
  14. Naray-Fejes-Toth A, Helms MN, Stokes JB and Fejes-Toth G. Regulation of sodium transport in mammalian collecting duct cells by aldosterone-induced kinase, SGK1: structure/function studies. Mol Cell Endocrinol 217: 197-202, 2004.
  15. Uc A, Stokes JB and Britigan BE. 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.
  16. Fenton RA, Chou CL, Ageloff S, Brandt W, Stokes JB and Knepper MA. Increased collecting duct urea transporter expression in Dahl salt-sensitive rats. Am J Physiol Renal Physiol 285: F143, 2003.
  17. Itani OA, Auerbach SD, Husted RF, Volk KA, Ageloff S, Knepper MA, Stokes JB and Thomas CP. 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.
  18. Masilamani S, Wang X, Kim GH, Brooks H, Nielsen J, Nielsen S, Nakamura K, Stokes JB and Knepper MA. Time course of renal Na-K-ATPase, NHE3, NKCC2, NCC, and ENaC abundance changes with dietary NaCl restriction. Am J Physiol Renal Physiol 283: F648-F657, 2002.
  19. Nakamura K, Stokes JB and McCray PB, Jr. Endogenous and exogenous glucocorticoid regulation of ENaC mRNA expression in developing kidney and lung. Am J Physiol Cell Physiol 283: C762-C772, 2002.
  20. Olakanmi O, Rasmussen GT, Lewis TS, Stokes JB, Kemp JD and Britigan BE. Multivalent metal-induced iron acquisition from transferrin and lactoferrin by myeloid cells. J Immunol 169: 2076-2084, 2002.
  21. Volk KA, Snyder PM and Stokes JB. Regulation of Epithelial Sodium Channel Activity through a Region of the Carboxyl Terminus of the alpha -Subunit. Evidence for Intracellular Kinase-Mediated Reactions. J Biol Chem 276: 43887-43893, 2001.
  22. Husted RF, Sigmund RD and Stokes JB. Mechanisms of inactivation of the action of aldosterone on collecting duct by TGF-b. Am J Physiol Renal Physiol 278: F425-F433, 2000.
  23. Naray-Fejes-Toth A, Fejes-Toth G, Volk KA and Stokes JB. SGK is a primary glucocorticoid-induced gene in the human. J Steroid Biochem Molec Biol 75: 51-56, 2000.
    Stokes JB. Physiologic resistance to the action of aldosterone. Kidney Int 57: 1319-1323, 2000.
  24. Stokes J. Understanding how aldosterone increases sodium transport. Am J Kidney Dis 36: 866-870, 2000.
  25. Volk KA, Husted RF, Snyder PM and Stokes JB. 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.
  26. McDonald FJ, Yang B, Hrstka RF, Drummond HA, Tarr DE, McCray PB, Stokes JB, Welsh MJ and Williamson RA. 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.
  27. Sayegh R, Auerbach SD, Li X, Loftus RW, Husted RF, Stokes JB and Thomas CP. Glucocorticoid induction of epithelial sodium channel expression in lung and renal epithelia occurs via trans-activation of a hormone response element in the 5' flanking region of the human epithelial sodium channel a subunit gene. J Biol Chem 274: 12431-12437, 1999.
  28. Thomas CP, Auerbach SD, Zhang C and Stokes JB. The structure of the rat amiloride-sensitive epithelial sodium channel gamma subunit gene and functional analysis of its promoter. Gene 228: 111-122, 1999.
  29. Watanabe S, Matsushita K, McCray PB and Stokes JB. Developmental expression of the epithelial Na+ channel in kidney and uroepithelia. Am J Physiol (Renal Physiol ) 276: F304-F314, 1999.

Links of Interest

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