Douglas C. Eaton, Ph.D.

Director, Center for Cell and Molecular Signaling

Distinguished Professor and Chair

Department of Physiology
Emory University School of Medicine
Atlanta, GA 30322

Ph.D., University of California, San Diego, 1971

Member of Graduate Programs:
Biochemistry, Cell and Developmental Biology

 
 
 
   

Email Address: douglas.eaton@emory.edu

Summary of Research Interests:

The goal of my research is to examine the cellular signaling mechanisms which control all aspects of cellular function including cell growth, division, and responses to external stimuli. To examine these signaling mechanisms, I use contemporary methods of cellular and molecular biology including patch voltage clamp methods and expression of cloned signaling molecules in Xenopus oocytes and other expression systems. There are three main areas of cellular signaling research in my laboratory. First, I have been particularly interested in the cellular responses which involve steroid hormones and other lipid molecules particulary as these molecules are responsible for regulation of total body sodium balance. This work has lead us recently to examine defects in cellular signaling which may be responsible for some types of hypertension and electrolyte disorders. Second, I have been examining the signaling mechanisms responsible for the responses of renal cells to growth factors and vasoactive substances like Angiotensin II. This work has direct relevance to understanding the renal pathology of diabetes. Finally, I am interested in the signaling mechanisms which control excitability of ion channels in nerve cells. This work may provide an understanding of the mechanism of action of general anesthetics.

Selected Publications:

Kemendy, A.E.; Eaton, D.C. Aldosterone alters the open probability of amiloride-blockable sodium channels in A6 epithelia. Am. J. Physiol. (Cell) 262:C825-C837; 1992.

Frace, A. M.; Eaton, D.C. Chemical modification of amino groups on calcium activated K+ channels of GH3 cells. Am. J. Physiol. (Cell) 263:C1081-C1087; 1992.

Ohara, A.; Matsunaga, H.; Eaton, D.C. G-protein activation inhibits amiloride-blockable, highly selective sodium channels in A6 cells. Am. J. Physiol. (Cell) 263:C352-C360; 1993.

Matsumoto, P. S.; Ohara, A.; Duchatelle, P.; Eaton, D.C. Tyrosine kinase regulates epithelial sodium transport in A6 cells. Am. J. Physiol. (Cell) 264:C246-C250; 1993.

Ling, B. N.; Kokko K. E.; Eaton D. C. PGE2 activates clusters of apical Cl- channels in principal cells via a cAMP-dependent pathway. J. Clin. Invest. 93:829-837, 1994.

Matsunaga, H; Ling, BN; and Eaton DC. Ca2+-permeable channel associated with platelet- derived growth factor receptor in mesangial cells. Am J Physiol (Cell). 267:C456-465, 1994.

Kokko, K.E.; Matsumoto, P.S.; Ling, B.N.; and Eaton, D.C. Effects of prostaglandin E2 on amiloride-blockable Na+ channels in a distal nephron cell line (A6). Am J Physiol (Cell) 267:C1414-1425, 1994.

Seal, E.E.; Eaton, D.C.; Gomez, L.M.; Ma, H.; Ling, B.N. Extracellular glucose reduces the responsiveness of mesangial cell ion channels to angiotensin II. Am J Physiol (Fluid and Electrolyte) 269:F389-F397, 1995.

Denson, D.D. ; Worrell, R.T.; and Eaton D.C. A possible role for phospholipase A2 in the action of general anesthetics. Am J Physiol (Cell). 270 :C636-C644, 1996.

Ling, B.N.;Zuckerman, J.B.; Lin, C.-M.; Harte, B.J.; McNulty, K.A.; Smith, P.R.; Gomez, L.; Worrell, R.T.; Eaton, D.C and Kleyman, T.R. Expression of the cystic fibrosis phenotype in a renal amphibian epithelial cell line. J. Biol. Chem. 272:594-600, 1997.

Ismailov, I.I.; Kieber-Emmons, T.; Lin, C.-M.; Berdiev, B.K.; Shylonsky, V.G.; Patton, H.K., Fuller, C.M.; Worrell, R.T.; Zuckerman, J.B.; Sun, W.; Eaton, D.C; Benos, D.J.; and Kleyman, T.R. Identification of an amiloride-binding domain within the alpha subunit of the epithelial sodium channel. J. Biol. Chem. 272:21075-21083, 1997.

Marrero, M.B., Venema, V.J., Ju, H., Li, B., Li, J., Eaton, D.C., and Venema, R.C. Regulation of the angiotensin II-induced JAK2 tyrosine phosphorylation. Roles of SHP-1 and SHP-2. Am J. Physiol. (Cell). 275:C1216-23, 1998.

Jain, L., Chen, X.-J., Brown, L.A., and Eaton, D.C. Nitric oxide inhibits lung sodium transport through a cGMP-mediated inhibition of epithelial sodium channels. Am J Physiol (Lung Cell & Molecular Biology). 274 :L475-L484, 1998.

Marrero, M.B.,Venema, R.C. Venema, V.J., Eaton, D.C. Angiotensin II-induced tyrosine phosphorylation of STAT1 is regulated by JAK2 and Fyn kinases and MKP-1 phosphatase. J. Biol. Chem. 273:30795-30800, 1998.

Stockand, J.D., N.F. Al-Baldawi, O.K. Al-Khalili, R.T. Worrell, and D.C. Eaton. S-Adenosyl-L-homocysteine hydrolase regulates aldosterone-induced Na+ transport. J Biol Chem 274:3842-3850, 1999.

Al-Baldawi, N.F., Stockand, J.D., Al-Khalili, O.K., Yue, G., Eaton, D.C. Aldosterone Induces Ras Methylation in A6 Epithelia. Am J Physiol 279:C429-C439, 2000.

Becchetti,A., Kemendy,A.E., Stockand,J.D., Sariban-Sohraby,S., and Eaton,D.C. Methylation Increases the Open Probability of the Epithelial Sodium Channel in A6 Epithelia. J Biol Chem 275:16550-16559, 2000.

Stockand,J.D., Bao,H.F., Schenck,J., Malik,B., Middleton,P., Schlanger,L.E., and Eaton,D.C. Differential effects of protein kinase C on the levels of epithelial Na+ channel subunit proteins. J Biol Chem 275:25760-25765, 2000.

Jain,L.; Chen, X.-J.; Ramosevac, S.; Brown, L.A.; Eaton, D.C. Expression of highly selective sodium channels in alveolar type II cells is determined by culture conditions. Am. J. Physiol. (Lung Cell Mol Physiol.) 280:L646-58, 2001.

Malik, B.; Schlanger, L.; Al-Khalili, O.; Bao, H.-F.; Yue, G.; Price, S.R.; Mitch, W.E.; Eaton, D.C. ENaC degradation in A6 Cells by the ubiquitin-proteasome proteolytic pathway. J. Biol. Chem. 276:12903-10, 2001.

Kleyman, T.R.; Zuckerman, J.B.; Middleton, P.; McNulty, K.; Hu, B.; Su, X.; An, B.; Eaton, D.C.; Smith, P.R. Cell surface expression and turnover of the alpha subunit of the epithelial sodium channel. Am. J. Physiol. (Renal): 281:F213-21, 2001.

Stockand, J.D., Zeltwanger, S.; Bao, H.-F.; Becchetti,A.; Worrell, R.T.; Eaton,D.C. S-adenosyl-L-homocysteine hydrolase is necessary for aldosterone-induced activity of epithelial Na+ channels. Am. J. Physiol. (Cell) 281:C773-85, 2001.

Worrell RT, Bao HF, Denson DD, Eaton DC. Contrasting effects of cPLA2 on epithelial Na+ transport. Am J Physiol Cell Physiol 281:C147-56, 2001.

Eaton,D.C.; Malik, B.; Saxena, N.C.; Al-Khalili, O.; Yue, G. Mechanisms of aldosterone's action on epithelial Na+ transport. J. Membrane Biol. 184:313-319, 2001.

Yue, G.; Merlin, D.; Selsted, M.E.; Lencer, W.I.; Madara, J.L.; Eaton,D.C. Cryptdin 3 forms anion selective channels in the cytoplasmic membranes of human embryonic kidney cells. Am. J. Physiol. Gastrointest. Liver Physiol. 282:G757-65, 2002.

Ma, H.-P.; Li, L.; Zhou, Z.H.; Eaton, D.C.; Warnock, D.G. ATP masks stretch activation of epithelial sodium channels in A6 distal nephron cells. Am. J. Physiol. (Renal) 282:F501-F505, 2002.

Yue, G.; Malik, B., Yue, G.; Eaton, D.C. Phosphatidylinositol 4,5-bisphosphate (PIP2) stimulates epithelial sodium channel activity in A6 cells. J. Biol. Chem. 277:11965-11969, 2002.

Amiri, F.; Shaw, S.; Wang, X.; Tang, J.; Waller, J.L.; Eaton, D.C.; Marrero, M.B. Angiotensin II activation of the JAK/STAT pathway in mesangial cells is altered by high glucose. Kidney Int. 61:1605-16, 2002.

Chen, X.-J.; Eaton, D.C.; Jain, L. Beta-adrenergic regulation of amiloride-sensitive lung sodium channels. Am. J. Physiol. Lung Cell Mol. Physiol. 282:L609-620, 2002.

Becchetti, A.; Malik,B.; Yue, G.; Duchatelle, P.; Al-Khalili, O.; Kleyman, T.R.; Eaton, D.C. Phosphatase inhibitors increase the open probability of ENaC in A6 cells. Am. J. Physiol. (Renal ) 283:F1030-F1045, 2002.

Fink, A.S.; Wang, Y.; Mendez, T.; Worrell, R.T.; Eaton, D.C.; Nguyen, T.D.; Lee, S.P. Angiotensin II evokes calcium-mediated signaling events in isolated dog pancreatic epithelial cells. Pancreas 25:290-5, 2002.

Wang, X.; Shaw, S.; Amiri, F.; Eaton, D.C.; Marrero, M.B. Inhibition of the Jak/STAT signaling pathway prevents the high glucose-induced increase in tgf-beta and fibronectin synthesis in mesangial cells. Diabetes 51:3505-9, 2002.

Matalon, S.; Lazrak, A.; Jain, L.; Eaton, D.C. Invited review: biophysical properties of sodium channels in lung alveolar epithelial cells. J. Appl. Physiol. 93:1852-9, 2002.

Rabih I. Bechara, R.I.; Brown, L.A.S.; Eaton, D.C.; Roman, J.; Guidot, D.M. AT2 receptor expression and apoptosis in alveolar epithelial cells of ethanol-fed rats. Alcohol Clin Exp Res. 27:1006-14, 2003.

Kelly O, Lin C, Ramkumar M, Saxena NC, Kleyman TR, Eaton DC. Characterization of an amiloride binding region in the alpha-subunit of ENaC. Am J Physiol Renal Physiol. 285:F1279-90, 2003.

Hardiman KM, McNicholas-Bevensee CM, Fortenberry J, Myles CT, Malik B, Eaton DC, Matalon S. Regulation of amiloride-sensitive Na+ transport by basal nitric oxide. Am J Respir Cell Mol Biol. 30:720-8, 2004.

Chen XJ, Seth S, Yue G, Kamat P, Compans RW, Guidot D, Brown LA, Eaton DC, Jain L. Influenza virus inhibits ENaC and lung fluid clearance. Am J Physiol Lung Cell Mol Physiol. 287:L366-73, 2004.

Byas-Smith MG, Li J, Szlam F, Eaton DC, Votaw JR, Denson DD. Isoflurane induces dopamine transporter trafficking into the cell cytoplasm. Synapse. 53(2):68-73, 2004.

Ma HP, Al-Khalili O, Ramosevac S, Saxena S, Liang YY, Warnock DG, Eaton DC. Steroids and exogenous gamma-ENaC subunit modulate cation channels formed by alpha-ENaC in human B lymphocytes. J Biol Chem.279:33206-12, 2004.

Niisato N, Eaton DC, Marunaka Y. Involvement of cytosolic Cl- in osmoregulation of alpha-ENaC gene expression. Am J Physiol Renal Physiol. 287:F932-9, 2004.

Eaton DC, Chen J, Ramosevac S, Matalon S, Jain L. Regulation of Na+ channels in lung alveolar type II epithelial cells. Proc Am Thorac Soc. 1:10-16, 2004.

Denson, D.D.; Li, J.; Wang, X.; Eaton, D.C. Activation of BK-channels in GH3 cells by c-PLA2-dependent G-protein signaling pathway. J Neurophysiol. 93:3146-56, 2005.

Holtzclaw, J.D.; Morris, L.; Pyatt, R.; Giver, C.; Hoey, J.; Gunn, R.B.; Eaton, D.C.; Haynes, J.K.; Eisen, A. FIRST: A New Model for Developing Future Science Faculty. J. College Science Teaching. in press. 2005.

Malik B, Yue Q, Yue G, Chen XJ, Price SR, Mitch WE, Eaton DC. Role of Nedd4-2 and poly-ubiquitination in epithelial sodium channel degradation in untransfected renal A6 cells expressing endogenous ENaC subunits. Am J Physiol Renal Physiol. 289:F107-16, 2005.

Helms MN, Yu L, Malik B, Kleinhenz DJ, Hart CM, Eaton DC. Role of SGK1 in nitric oxide inhibition of ENaC in Na+-transporting epithelia. Am J Physiol Cell Physiol. 289:C717-26, 2005.



Current support:

Title: “Regulation of Na+ Transport in Tight Epithelia”
Principal Investigator: Douglas C. Eaton, Ph.D.
Agency: NIH NIDDK Type: 2R37 DK-37963
Years 16 - 25 Period: 08/01/02 - 07/31/12

This grant examines the mechanisms by which epithelial sodium channels can be regulated by aldosterone, G-proteins, and inositol lipids; and examines these regulatory cascades for their ability to alter sodium channel activity in a physiological context.

Title: “Regulation of Lung Sodium Channels”
Principal Investigator: Lucky Jain, M.D.
Agency: NIH NHLBI Type: 1R01HL63306-01
Years 1 - 4 Period: 05/01/01 - 04/31/05

This is a grant to investigate the mechanisms of regulation of sodium transport in lung alveolar type II cells with particular emphasis on the control of lung surface fluid and edema.
Role: Co-PI

Title: “ENaC Assembly, trafficking, and degradation in lung”
Principal Investigator: Douglas Eaton, Ph.D.
Agency: NIH NHLBI Type: 1R01HL071621
Years 1 - 4 Period: 01/01/03 - 12/31/07

This is a grant to investigate the mechanisms of ENaC Assembly, trafficking, and degradation in lung alveolar type II cells.

Title: “Project 2: Ethanol effects on lung sodium and chloride transport and fluid clearance”
Principal Investigator: Douglas Eaton, Ph.D.
Agency: NIH NIAAA Type: 1P50 AA-013757
Years 1 - 5 Period: 01/01/03 - 12/31/08

The aims of this project are to use single channel methods to examine signaling mechanisms which regulate ENaC expression and the effects of chronic alcoholism. This is one project of a larger Center Grant, "Chronic Alcoholism and Lung Pathology" of which Dr. David Guidot is the Program Director. Role: Project Investigator

Title: “Cellular Signaling and Kidney Function”
Program Director: Douglas Eaton, Ph.D.
Agency: NIH NIDDK Type: 2P01 DK-61521
Years 1 - 5 Period: 09/30/04 - 07/31/09

The aims of this program (consisting of 4 separate projects) are to examine the cell biology of renal transport proteins that are responsible for maintaining normal homeostatic balance for sodium, chloride, hydrogen ion, and urea.

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