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James Graham Brown Endowed Chair of Cancer Biology; Professor of Medicine, and Pharmacology & Toxicology; Deputy Director, James Graham Brown Cancer Center; Leader, Molecular Targets Program, James Graham Brown Cancer Center
Research ProgramMolecular Targets
Research Interests
John Eaton has had a long-term interest in free radicals and the damaging effects of biological oxidation events. His laboratory investigates mechanisms of iron-mediated cell damage in chronic iron overload and exposure to various pro-oxidant drugs (including cancer chemotherapies). A second research focus involves mitochondria, organelles which provide most cellular energy. Unfortunately mitochondria are also the major producers of oxidants inside cells and mitochondrial dysfunction, with attendant increases in reactive oxygen production, can lead to cell death. Dr. Eaton is exploring mechanisms of possible use in modulating mitochondrial functions and permitting cells to survive otherwise lethal insults. Finally, Dr. Eaton and his colleagues are pursuing early-stage investigations into an anti-cancer vaccine made of embryonic stem cells. In mice, this vaccine prevents the outgrowth of transplantable and carcinogen-induced lung cancers.
Education
B.A., Florida State University, 1963
M.A., University of Florida, 1964
M.S., University of Michigan, 1966
Ph.D., University of Michigan, 1969
M.D.hc, University of Linkoping, Sweden, 2001
Research and Professional Experience
1970-1972
Professor, Department of Anthropology, Washington University, St. Louis, MO
1972-1977
Assistant Professor, Department of Medicine, University of Minnesota, Minneapolis, MN
1977-1979
Associate Professor, Department of Medicine, University of Minnesota, Minneapolis
1979-1990
Director, Division of Medical Genetics, University of Minnesota, Minneapolis
1979-1992
Professor, Department of Medicine, University of Minnesota, Minneapolis
1979-1992
Professor, Department of Laboratory Medicine/Pathology, University of Minnesota, Minneapolis
1992-1996
Professor, Department of Pathology/Laboratory Medicine, Albany Medical College, Albany, NY
1992-1997
Director, Division of Experimental Pathology, Albany Medical College, Albany, NY
1992-1996
Professor, Department of Biochemistry/Molecular Biology, Albany Medical College, Albany, NY
1994-1996
Professor, Department of Physiology/Cell Biology, Albany Medical College, Albany, NY
1996-2000
Professor, Department of Pediatrics, Baylor College of Medicine, Houston, TX
2000-Present
Professor, Departments of Medicine and Pharmacology & Toxicology, University of Louisville, KY
2000-Present
James Graham Brown Endowed Chair of Cancer Biology, Brown Cancer Center, University of Louisville
2001-Present
Deputy Director, James Graham Brown Cancer Center, University of Louisville
2001-Present
Leader, Molecular Targets Program, James Graham Brown Cancer Center, University of Louisville
Selected Awards and Professional Honors
1966-1969
USPHS Graduate Training Grant (Human Genetics)
1978-1983
NIH Research Career Development Award
1988-1992; 1998-2002
Member, Hematology-2 Study Section, National Heart, Lung & Blood Institute, NIH
1996-2003
Immediate Past-Editor, Redox Report
2001, M.D.(hc), University of Linkoping, Sweden
2003-present
Member, Governance Board of the Kentucky Lung Cancer Research Fund, Commonwealth of Kentucky
2006-present
Member, Review Panel for the California Tobacco Research Program
2006-present
Member, Scientific Advisory Committee, The Bosch Institute, Sydney, Australia
2007
Mint Jubilee Scientist of the Year
Current Holder of ten US Letters Patents
PublicationsQian M, Eaton JW. Glycochelates and etiology of diabetic peripheral neuropathy. Free Radic Biol Med 28:652-6, 2000
Borovikova L, Ivanova S, Zhang M, Yang H, Botchkina GI, Watkins L, Wang H, Abumrad N, Eaton JW, Tracey KJ. Vagus nerve stimulation attenuates the systemic inflammatory response to endotoxin. Nature 405:458-62, 2000
Zhao M, Eaton JW, Brunk UT. Protection against oxidant-mediated lysosomal rupture: a new anti-apoptotic activity of Bcl-2? FEBS Lett 485:104-8, 2000
Goth L, Eaton JW. Hereditary catalase deficiencies and increased risk of type II diabetes. Lancet 356:1820-1, 2000
Brunk UT, Neuzil J, Eaton JW. Lysosomal involvement in apoptosis. Redox Report 6:91-7, 2001
Hu WJ, Eaton JW, Tang L. Molecular basis of biomaterial-mediated inflammatory responses. Blood 98:1231-8, 2001
Telang S, Vimr E, Mahoney JR, Law I, Lundqvist-Gustafsson H, Qian M, Eaton JW. Strain-specific iron-dependent virulence in Escherichia coli. J Infec Dis 184:159-65, 2001
Li W, Dalen H, Eaton JW, Yuan XM. Apoptotic death of inflammatory cells in human atheroma. Atheroscl Thromb Vasc Biol 21:1124-30, 2001
Zhao M, Brunk UT, Eaton JW. Delayed oxidant-induced cell death involves activation of phospholipase A2. FEBS Letts 509:399-404, 2001
Zhao M, Eaton JW, Brunk UT. Bcl-2 phosphorylation is required for inhibition of oxidative stress-induced lysosomal leak and ensuing apoptosis. FEBS Letts 509:405-12, 2001
Ivanova S, Batliwalla F, Borovikova L, Huang J, Al-Abed Y, Eaton JW, Gregersen P, Shohami E, Connolly E, Tracey K. Neuroprotection in cerebral ischemia by neutralization of 3-aminopropanal. Proc Natl Acad Sci USA 99:5579-84, 2002
Neuzil J, Zhao M, Ostermann G, Kågedal K, Sticha M, Gellert N, Weber C, Eaton JW, Brunk UT. Tocopheryl succinate induces apoptosis by causing lysosomal instability. Biochem J 352:709-15, 2002
Zhao M, Liu Y, Bao M, Kato Y, Han J, Eaton JW. Vascular smooth muscle cell proliferation requires both p38 and BMK1 MAP kinases. Arch Biochem Biophys 400:199-207, 2002
Yang H, Wang H, Vishnubhakat KM, Che J, Ombrfellino M, Borovikova LV, Roth J, Eaton JW, Tracey KJ. Globin attenuates lipopolysaccharide-induced TNF release and lethality. Shock 27:485-90, 2002
Eaton JW, Qian M. Molecular bases of cellular iron toxicity. Free Radic Biol Med 32:933-40, 2002
Jeney V, Balla J, Yachic A, Varga Z, Vercellotti GM, Eaton JW, Balla G. Pro-oxidant and cytotoxic effects of circulating heme. Blood 100:879-87, 2002
Eaton JW, Qian M. Interactions of copper with glycated proteins: possible involvement in the etiology of diabetic neuropathy. Mol Cell Biochem 234-235:135-42, 2002
Li W, Yuan XM, Ivanova S, Tracey KJ, Eaton JW, Brunk UT. 3-Aminopropanal, formed during cerebral ischemia, is a potent lysosomotropic neurotoxin. Biochem J 371:429-36, 2003
Yu Z, Persson HL, Eaton JW, Brunk UT. Intralysosomal iron: a major determinant of oxidant-induced cell death. Free Radic Biol Med 34:1243-52, 2003
Persson HL, Yu Z, Tirosh D, Eaton JW, Brunk UT. Prevention of oxidant-induced cell death by lysosomotropic iron chelators. Free Radic Biol Med 34:1295-1305, 2003
Zhao M, Antunes F, Eaton JW, Brunk UT. Lysosomal enzymes promote mitochondrial oxidant production, cytochrome c release and apoptosis. Eur J Biochem 270:3778-86, 2003
Yu Z, Eaton JW, Persson HL. The radioprotective agent, amifostine, suppresses the reactivity of intralysosomal iron. Redox Rep 8:347-55, 2003
Terman A, Dalen H, Eaton JW, Neuzil J, Brunk UT. Mitochondrial recycling and aging of cardiac myocytes: role of autophagocytosis. Exp Gerontol 38:863-76, 2003
Li J, Gao X, Qian M, Eaton JW. Mitochondrial metabolism underlies hyperoxic cell damage. Free Radic Biol Med 36:1460-70, 2004
Campian JL, Qian M, Gao X, Eaton JW. Oxygen tolerance and coupling of mitochondrial electron transport. J Biol Chem 279:46580-7, 2004
Busuttil SJ, Ploplis VA, Castellino FJ, Tang L, Eaton JW, Plow EF. A central role for plasminogen in the inflammatory response to biomaterials. J Thromb Haemost 2(10):1798-805, 2004.
Persson LH, Kurz T, Eaton JW, Brunk UT. Radiation-induced cell death: Importance of lysosomal destabilization. Biochem J 389(Pt 3):877-84, 2005
Balla J, Vercellotti GM, Jeney V, Yachie A, Varga Z, Eaton JW, Balla G. Heme, heme oxygenase and ferritin in vascular endothelial cell injury. Mol Nutr Food Res 49(11):1030-43, 2005
Gao X, Qian M, Campian JL, Clark DR, Burke TJ, Eaton JW, McGregor WG. Cytotoxic and mutagenic effects of tobacco-borne free fatty acids. Free Radic Biol Med 40:165-72, 2006
Ujhelyi L, Balla G, Jeney V, Varga Z, Nagy E, Vercellotti GM, Agarwal A, Eaton JW, Balla J. Hemodialysis reduces inhibitory effect of plasma ultrafiltrate on LDL oxidation and subsequent endothelial reactions. Kidney Int 69:144-51, 2006
Telang S, Yalcin A, Clem AL, Bucala R, Lane AN, Eaton JW, Chesney J. Ras transformation requires metabolic control by 6-phosphofructo-2-kinase. Oncogene 25(55):7225-34, 2006.
Li W, Ostblom M, Xu LH, Hellsten A, Leanderson P, Liedberg B, Brunk UT, Eaton JW, Yuan XM. Cytocidal effects of atheromatous plaque components: the death zone revisited. FASEB J 20(13):2281-90, 2006
Campian JL, Gao X, Qian M, Eaton JW. Cytochrome C oxidase activity and oxygen tolerance. J Biol Chem 282(17):12430-8, 2007
Telang S, Clem AL, Eaton JW, Chesney J. Depletion of ascorbic acid restricts angiogenesis and retards tumor growth in a mouse model. Neoplasia 9(1):47-56, 2007
Jiang Y, Reynolds C, Xiao C, Feng W, Zhou Z, Rodriguez W, Tyagi SC, Eaton JW, Saari JT, Kang YJ. Dietary copper supplementation reverses hypertrophic cardiomyopathy induced by chronic pressure overload in mice. J Exp Med 204(3):657-66, 2007
Clem AL, Sims J, Telang S, Eaton JW, Chesney J. Virus detection and identification using random multiplex (RT)-PCR with 3'-locked random primers. Virol J 4(1):65, 2007
Zdolsek J, Eaton JW, Tang L. Histamine release and fibrinogen adsorption mediate acute inflammatory responses to biomaterial implants in humans. J Transl Med 5(1):31, 2007
Balla J, Vercellotti GM, Jeney V, Yachie A, Varga Z, Jacob HS, Eaton JW, Balla G. Heme, heme oxygenase, and ferritin: How the vascular endothelium survives (and dies) in an iron-rich environment. Antioxid Redox Signal 9(12):2119-37, 2007
Brunk UT, Eaton JW. Peroxide hormesis? A commentary on "Hydrogen peroxide inhibits caspase-dependent apoptosis by inactivating procaspase-9 in an iron-dependent manner". Free Radic Biol Med 43(10):1372-3, 2007
Kakar SS, Jin H, Hong B, Eaton JW, Kang KA. LHRH receptor targeted therapy for breast cancer. Adv Exp Med Biol 614:285-96, 2008
Mehta JP, Campian JL, Guardiola J, Cabrera JA, Weir EK, Eaton JW. Generation of oxidants by hypoxic human pulmonary and coronary smooth-muscle cells. Chest 133(6):1410-4, 2008
Brewer BG, Mitchell RA, Harandi A, Eaton JW. Embryonic vaccines against cancer: An early history. Exp Mol Pathol 86(3):192-7, 2009
Jeney V, Komódi E, Nagy E, Zarjou A, Vercellotti GM, Eaton JW, Balla G, Balla J. Supression of hemin-mediated oxidation of low-density lipoprotein and subsequent endothelial reactions by hydrogen sulfide (H(2)S). Free Radic Biol Med 46(5):616-23, 2009
Gao X, Campian JL, Qian M, Sun XF, Eaton JW. Mitochondrial DNA damage in iron overload. J Biol Chem 284(8): 4767-75, 2009
Lee JY, Prineas RJ, Eaton JW. Heritability of erythrocyte sodium permeability: a possible genetic marker for hypertension. Ann Clin Lab Sci 39(3):241-50, 2009
Jenson B, Eaton JW, Miller DM. Cancer research at the James Graham Brown Cancer Center, University of Louisville. Exp Mol Pathol 86(3):139-40, 2009
Lee JY, Prineas RJ, Eaton JW. Heritability of erythrocyte sodium permeability: a possible genetic marker for hypertension. Ann Clin Lab Sci 39(3):241-50, 2009
Yalcin A, Clem B, Makoni S, Clem A, Nelson K, Thornburg J, Siow D, Lane AN, Brock SE, Goswami U, Eaton JW, Telang S, Chesney J. Selective inhibition of choline kinase simultaneously attenuates MAPK and PI3K/AKT signaling. Oncogene 29(1):139-49, 2010
Hebbel RP, Vercellotti GM, Pace BS, Solovey AN, Kollander R, Abanonu CF, Nguyen J, Vineyard JV, Belcher JD, Abdulla F, Osifuye S, Eaton JW, Kelm RJ Jr, Slungaard A. The HDAC inhibitors trichostatin A and suberoylanilide hydroxamic acid exhibit multiple modalities of benefit for the vascular pathobiology of sickle transgenic mice. Blood 2010 Jan 6. [Epub ahead of print]
Sharma PK, Singh R, Novakovic KR, Eaton JW, Grizzle WE, Singh S. CCR9-mediates PI3K/AKT dependent anti-apoptotic signals in prostate cancer cells and inhibition of CCR9-CCL25 interaction enhances the cytotoxic effects of etoposide. Int J Cancer 2010 Feb 2. [Epub ahead of print]
Related StoriesResearchers at U of L's Brown Cancer Center
Develop Vaccine that Prevents Lung Cancer in Mice
Contact InfoCTR Building
505 South Hancock Street
Louisville, KY 40202
Phone: (502) 852-1075
Fax: (502) 852-3661
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