Department of Internal Medicine
John B. Stokes, M.D.
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-b and oxygen. 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 is involved with several clinical research activities. He 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. Dr. Stokes also chairs the Steering Committee for ASSESS-AKI, a multicenter study to analyze the outcomes and prognosis of patients who survive an episode of acute kidney injury.
Honors, Awards, and Organizations
- Alexander von Humboldt Prize
- Alpha Omega Alpha
- American Association for the Advancement of Science
- Diplomate, American Board of Internal Medicine
- American College of Physicians, Fellow
- American Heart Association Council for High Blood Pressure Research, Fellow
- Council on Kidney Disease, Established Investigator Award
- American Physiological Society
- International Society of Nephrology
- American Society for Clinical Investigation
- American Society for Nephrology, Fellow
- Association of American Physicians
- American Clinical and Climatological Association
- Central Society for Clinical Research
- Editorial Board: American Journal of Kidney Disease, 1997-2001
- Editorial Board: American Journal of Physiology : Renal, Fluid, and Electrolyte Metabolism 1989-1996
- Editorial Board: Journal of Clinical Investigation, 1985-1990
- NIH Physiology Study Section 1984-1988
- Secretary-Treasurer, American Society of Nephrology, 1997-2003
- Consulting Editor, Journal of Clinical Investigation, 1997-2003
- President's Medal of the American Society of Nephrology 2003
- Daugirdas,J.T., Depner,T.A., Greene,T., Levin,N.W., Chertow,G.M., Rocco,M.V., and Stokes,J.B. 2010. Effects of reduced intradialytic urea generation rate and residual renal clearance on modeled urea distribution volume and Kt/V in conventional, daily, and nocturnal dialysis. Semin. Dial. 23:19-24.
- Stein,C.S., Yancey,P.H., Martins,I., Sigmund,R.D., Stokes,J.B., and Davidson,B.L. 2010. Osmoregulation of ceroid neuronal lipofuscinosis type 3 in the renal medulla. Am J Physiol Cell Physiol 298:C1388-C1400.
- Uc,A., McDonagh,A.F., and Stokes,J.B. 2010. Metabolism of haem in Caco-2 cells. Exp. Physiol 95:296-303.
- Stokes,J.B., Haupt,A., Molitoris,B.A., Kokemueller,P., and Ibrahim,T. 2009. ASN policy on managing conflicts of interest. J Am Soc Nephrol 20:1853-1859.
- Stokes,J.B., Berns,A.S., Henrich,W.L., McKinney,T.D., Molitoris,B.A., and Palmer,B.F. 2009. Managing conflicts of interest: the road ahead. J Am Soc Nephrol 20:1860-1862.
- Walder,R.Y., Yang,B., Stokes,J.B., Kirby,P.A., Cao,X., Shi,P., Searby,C.C., Husted,R.F., and Sheffield,V.C. 2009. Mice defective in Trpm6 show embryonic mortality and neural tube defects. Hum. Mol Genet 18:4367-4375.
- Stokes,J.B., Graw,K.S., Dengel,L.T., Swenson,B.R., Bauer,T.W., Slingluff,C.L., Jr., and Ledesma,E.J. 2009. Patients with Merkel cell carcinoma tumors < or = 1.0 cm in diameter are unlikely to harbor regional lymph node metastasis. J Clin Oncol. 27:3772-3777.
- Holstein,S.A., Stokes,J.B., and Hohl,R.J. 2009. Renal failure and recovery associated with second-generation Bcr-Abl kinase inhibitors in imatinib-resistant chronic myelogenous leukemia. Leuk. Res 33:344-347.
- Shi,P.P., Cao,X.R., Sweezer,E.M., Kinney,T.S., Williams,N.R., Husted,R.F., Nair,R., Weiss,R.M., Williamson,R.A., Sigmund,C.D. et al 2008. Salt-sensitive hypertension and cardiac hypertrophy in mice deficient in the ubiquitin ligase Nedd4-2. Am J Physiol Renal Physiol 295:F462-F470.
- Lee,C.J., Scheiman,J., Anderson,M.A., Hines,O.J., Reber,H.A., Farrell,J., Kochman,M.L., Foley,P.J., Drebin,J., Oh,Y.S. et al 2008. Risk of malignancy in resected cystic tumors of the pancreas < or =3 cm in size: is it safe to observe asymptomatic patients? A multi-institutional report. J Gastrointest. Surg. 12:234-242.
- Husted,R.F., Volk,K.A., Sigmund,R.D., and Stokes,J.B. 2007. Discordant effects of corticosteroids and expression of subunits on ENaC activity. Am J Physiol Renal Physiol 293:F813-F820.
- Shi,P.P., Cao,X.R., Qu,J., Volk,K.A., Kirby,P., Williamson,R.A., Stokes,J.B., and Yang,B. 2007. Nephrogenic diabetes insipidus in mice caused by deleting COOH-terminal tail of aquaporin-2. Am J Physiol Renal Physiol 292:F1334-F1344.
- Uc,A., Reszka,K.J., Buettner,G.R., and Stokes,J.B. 2007. Tin protoporphyrin induces intestinal chloride secretion by inducing light oxidation processes. Am J Physiol Cell Physiol 292:C1906-C1914.
- Young,J.S., Stokes,J.B., Denlinger,C.E., and Dubose,J.E. 2007. Proactive versus reactive: the effect of experience on performance in a critical care simulator. Am J Surg. 193:100-104.
- Cao,X.R., Shi,P.P., Sigmund,R.D., Husted,R.F., Sigmund,C.D., Williamson,R.A., Stokes,J.B., and Yang,B. 2006. Mice heterozygous for beta-ENaC deletion have defective potassium excretion. Am J Physiol Renal Physiol 291:F107-F115.
- Olakanmi,O., Stokes,J.B., and Britigan,B.E. 2005. 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.
- Itani,O.A., Stokes,J.B., and Thomas,C.P. 2005. Nedd4-2 isoforms differentially associate with ENaC and regulate its activity. Am J Physiol Renal Physiol 289:F334-F346.
- Uc,A., Husted,R.F., Giriyappa,R.L., Britigan,B.E., and Stokes,J.B. 2005. Hemin induces active chloride secretion in Caco-2 cells. Am J Physiol Gastrointest. Liver Physiol 289:G202-G208.
- Volk,K.A., Husted,R.F., Sigmund,R.D., and Stokes,J.B. 2005. Overexpression of the epithelial Na+ channel gamma subunit in collecting duct cells: interactions of Liddle's mutations and steroids on expression and function. J Biol. Chem. 280:18348-18354.
- Fernandez-Llama,P., Ageloff,S., Fernandez-Varo,G., Ros,J., Wang,X., Garra,N., Esteva-Font,C., Ballarin,J., Barcelo,P., Arroyo,V. et al 2005. Sodium retention in cirrhotic rats is associated with increased renal abundance of sodium transporter proteins. Kidney Int 67:622-630.