148 Whitehead Bldg., 615 Michael St.
Atlanta, GA 30322
404 727-5875 Phone
B.A. with Highest Honors, Southern Methodist University, 1968 - 1972
PhD in Biochemistry, Duke University, 1972 - 1976
MD Duke University, 1976 - 1977
- Reactive Oxygen Species (ROS)
Studies focus on reactive oxygen species (ROS) such as superoxide and hydrogen peroxide, and their biological roles, for example, in innate immunity, mitogenic growth, apoptosis, angiogenesis, and biosynthesis/ remodelling of extracellualr matrix. Starting in 1999, we described a new family of ROS-generating enzymes, the Nox/Duox family. This group of enzymes catalyzes the regulated generation of superoxide in response to signals including hormones, growth factors and immune mediators. The enzymology and regulation of ROS generation by the Nox enzymes and their regulatory proteins is an active area of investigation in our group. The biological function of these enzymes is being investigate in various model systems including cell culture, Drosophila melanogaster, C. elegans and mouse. In addition, the function of these enzymes in pathological conditions including cancer and atherosclerosis, and in normal aging is under active investigation. These enzymes now provide novel targets for development of anti-cancer and anti-arteriosclerotic drugs, which are currently under development by our group. These are predicted to be useful in the treatment and prevention of hypertension, atherosclerosis, and certain forms of cancer. The laboratory uses multi-disciplinary approaches ranging from enzymology and biochemistry to cell biology to animal models.
Named Eminent Scientist of the Year 2003 by International Research Promotion Council, 2003
NIH Research Career Development Award, 1982-1987
Elected Teacher of the Year by the Medical School Class of 1985, 1981
Insurance Medical Scientist Scholarship from Prudential Insurance Company, 1974-1977
Phi Beta Kappa, 1971
Burnham, D.N., Tyagi, S.R., Uhlinger, D.J., and Lambeth, J.D. (1989) "Diacylglycerol Generation and Phosphoinositide Turnover in Human Neutrophils: Effects of Particulate versus Soluble Stimuli", Arch. Biochem. Biophys. 269, 345-353.
Tyagi, S.R., Burnham, D.N. and Lambeth, J.D. (1989) "On the Biological Occurrence and Regulation of 1-Acyl and 1-O-Alkyl-Diradylylycerols in Human Neutrophils: Selective Destruction of Diacyl Species Using Rhizopus Lipase" J. Biol. Chem. 264, 12977-12982.
Lambeth, J.D. and Xu, X.X. (1989) "Cholesterol Sulfate: A Naturally-Occurring Inhibitor of Cholesterol Side-Chain Cleavage Which Functions at the Level of Intramitochondrial Cholesterol Translocation" Endocrine Research 15, 85-99.
Xu, X.X. and Lambeth, J.D. (1989) "Cholesterol Sulfate is a Naturally Occurring Inhibitor of Steroidogenesis in Isolated Rat Adrenal Mitochondria" J. Biol. Chem. 264, 7222-7227.
Lambeth, J.D. (1989) "Introduction to: Minireview Series on the Respiratory Burst Oxidase and its Regulation", J. Bioenergetics and Biomembranes 20, 633-635.
Lambeth, J.D. (1989) "Activation of the Respiratory Burst Oxidase in Neutrophils: On the Role of Membrane-Derived Second Messengers, Ca++ and Protein Kinase C" J. Bioenergetics and Biomembranes 20, 709-733.
Merrill, A.H., Jr., Nimkar, S., Menaldino, D., Hannun, Y.A., Loomis, C., Bell, R.M., Tyagi, S.R., Lambeth, J.D., Stevens, V.L., Hunter, R., and Liotta, D.C. (1989) "Structural requirements for long-chain (sphingoid) base inhibition of protein kinase C in vitro and for the cellular effects of these compounds" Biochemistry, 28, 3138-3145.
Tamura, M., Tamura, T., Tyagi, S.R., and Lambeth, J.D. (1988) "The Superoxide-Generating Respiratory Burst Oxidase of Human Neutrophil Plasma Membrane: Phosphatidylserine as an Effector of the Activated Enzyme" J. Biol. Chem. 263, 17621-17626.
Fowler, W.T.,Jr., Lambeth, J.D., and Powell, G.L. (1988) "Photoreactive Cardiolipin Analogs" Chem. Phys. Lipids 47, 261-271.
Nishimoto, Y., Tamura, M., and Lambeth, J.D. (1988) "A Menadione-Stimulated Pyridine Nucleotide Oxidase from Resting Bovine Neutrophil Membranes: Purification, Properties, and Immunochemical Cross-Reactivity with the Human Neutrophil NADPH Oxidase" J. Biol. Chem. 263, 11657-11663.
Tyagi, S.R., Tamura, M., Burnham, D. and Lambeth, J.D. (1988) "Phorbol Myristate Acetate Augments Chemoattractant-induced Diglyceride Generation in Human Neutrophils, but Inhibits Phosphoinositide Hydrolysis: Implications for the Mechanism of PMA Priming of the Respiratory Burst" J. Biol. Chem. 263, 13191-13198.
Lambeth, J.D., Burnham, D.N. and Tyagi, S.R. (1988) "Sphinganine Effects on Chemoattractant-induced Diacylglycerol Generation, Calcium Fluxes, Superoxide Production, and on Cell Viability in the Human Neutrophil: Delivery of Sphinganine with Bovine Serum Alubumin Minimizes Cytotoxicity without Affecting Inhibition of the Respiratory Burst" J. Biol. Chem. 263, 3818-3822.
Deli, E., Kiss, Z., Wilson, E., Lambeth, J.D., and Kuo, J.F. (1987) "Immunocytochemical Localization of Protein Kinase C in Resting and Activated Human Neutrophils" FEBS Lett. 221, 365-369.
Lambeth, J.D. (1987) "Cytochrome P-450scc: Specificity and Properties of the Cholesterol Binding Site" Endocrine Research 12, 371-392.
Wilson, E., Laster, S.M., Gooding, L.R. and Lambeth, J.D. (1987) "Platelet-derived growth factor stimulates phagocytosis and blocks agonist-induced activation of the neutrophil oxidative burst: A possible cellular mechanism to protect against oxygen radical damage" Proc. Nat. Acad. Sci., U.S.A. 84, 2213-2217.
Wilson, E., Rice, W.G., Kinkade, J.M., Jr., Merrill, A.H., Arnold, R.A., and Lambeth, J.D. (1987) "Protein Kinase C Inhibition by Sphingoid Long-Chain Bases: Effects on Secretion in Human Neutrophils" Arch. Biochem. Biophys. 259, 204-214.
Lambeth, J.D., Xu, X.X., and Glover (1987) "Cholesterol sulfate inhibits adrenal mitochondrial cholesterol side chain cleavage at a site distinct from cytochrome P-450scc: Evidence for an intramitochondrial cholesterol translocator" J. Biol. Chem. 262, 9181-9188.
Tuls, J., Geren, L., Lambeth, J.D. and Millett, F. (1987) "The Use of a Specific Fluorescence Probe to Study the Interaction of Adrenodoxin with Adrenodoxin Reductase and Cytochrome P-450scc" J. Biol. Chem. 262, 10020-10025.
Tribble, D.L., Glover, M.R., and Lambeth, J.D. (1987) "Pregnenolone Production by Adrenal Mitochondria: A New HPLC Analytical Method for Cholesterol Side Chain Cleavage" J. Chromatog. 414, 411-416.
Wilson, E., Olcott, M.C., Bell, R.M., Merrill, A.H., and Lambeth, J.D. (1986) "Inhibition of the Oxidative Burst in Human Neutrophils by Long-Chain Bases: Role of Protein Kinase C in Activation of the Burst" J. Biol. Chem. 261, 12616-12623.
Stevens, V.L., Lambeth, J.D., and Merrill, A.H. (1986) "Use of Cytochrome P-450scc to Measure Cholesterol-Lipid Interactions", Biochemistry 25, 4287-4292.
Stevens, V.L. and Lambeth, J.D. (1985) "ACTH Regulation of Mitochondrial Compartment Volumes in Rat Adrenal Cortex: On the Mechanism of Hormonal Control of Steroidogenesis." Archives Biochem. Biophys. 242, 324-327.
Nisimoto, Y. and Lambeth, J.D., (1985) "Cross-Linking of Phospholipid Vesicle-Associated NADPH-cytochrome P-450 Reductase and Cytochrome b5 by a Water-Soluble Carbodiimide," Archives Biochem. Biophys. 241, 386-396.
Lambeth, J.D. and Kriengsiri, S. (1985) "Cytochrome P-450scc-Adrenodoxin Interactions: Ionic Effects on Binding and Regulation of Cytochrome Reduction by Bound Steroid Substrates." J. Biol. Chem. 260, 8810-8816.
Nisimoto, Y., Wilson, E., Heyl, B.H. and Lambeth, J.D. (1985) "NADH Dehydrogenase from Bovine Neutrophil Membranes: Purification and Properties" J. Biol. Chem. 261, 285-290.
Heyl, B.H., Tyrrell, D.J., and Lambeth, J.D. (1985) "Cytochrome P-450scc-Substrate Interactions: Role of the 3¿- and Side Chain Hydroxyls in Binding to Oxidized and Reduced Forms of the Enzyme" J. Biol. Chem. 261, 2743-2749.
Lambeth, J.D. and Stevens, V.L. (1985) "Cytochrome P-450scc: Enzymology, and the Regulation of Intramitochondrial Cholesterol Delivery to the Enzyme," Endocrine Research 10, 283-309.
Kamin, H., Batie, C., Lambeth, J.D., Lancaster, J., Graham, L. and Salerno, J.C. (1985) "Paramagnetic Probes of Multicomponent Electron Transfer Systems" Biochemical Society Trans. 13, 615-618.
Pember, S.O., Heyl, B.H., Kinkade, J.M. and Lambeth, J.D. (1984) "Cytochrome b558 from (Bovine) Granulocytes: Partial Purification from Triton X-114 Extracts, and Properties of the Isolated Cytochrome," J. Biol. Chem. 259, 10590-10595.
Lambeth, J.D., Geren, L.M. and Millett, F. (1984) "Adrenodoxin Interaction with Adrenodoxin Reductase and Cytochrome P-450ssc: Cross-Linking of Protein Complexes and Effects of Adrenodoxin Modification by EDC," J. Biol. Chem. 258, 10025-10029.
Vahouny, G.V., Chanderbhan, R., Noland, B.J., Irwin, D., Dennis, P., Lambeth, J.D. and Scallen, T. (1983) "Sterol Carrier Protein 2: Identification of Adrenal SCP2 and Site of Action for Mitochondrial Cholesterol Utilization." J. Biol. Chem. 258, 11731-11737.
Stevens, V.I., Aw. T.Y., Jones, D.P. and Lambeth, J.D. (1983) "Oxygen-Dependence of Adrenal Cortex Cholesterol Side Chain Cleavage: Implications in the Rate-Limiting Steps in Steroidogenesis." J. Biol. Chem. 259, 1174-1179.
Lambeth, J.D. and Pember, S.O. (1983) "Cytochrome P-450scc-Adrenodoxin Complex: Reduction Properties of the Substrate-Associated Cytochrome and Relation of the Reduction States of Heme and Iron Sulfur Centers to Association of the Proteins." J. Biol. Chem. 258, 5596-5602.
Pember, S.O., Powell, G.L. and Lambeth, J.D. (1983) "Cytochrome P-450scc-Phospholipid Interactions: Demonstration of a Cardiolipin Binding Site and Thermodynamics of Enzyme Interactions with Cardiolipin, Cholesterol, and Adrenodoxin." J. Biol. Chem. 258, 3198-3206.
Lambeth, J.D. (1983) "22-Ketocholesterol: A Potent Competitive Inhibitor of Cytochrome P-450scc-Dependent Side-Chain Cleavage of Cholesterol" Mol. Pharm. 23, 743-747.
Lambeth, J.D., Seybert, D.W., Lancaster, J.R., Salerno, J. and Kamin, H. (1982) "Steroidogenic Electron Transport in Adrenal Cortex Mitochondria." Mol. Cell. Biochem. 45, 13-31.
Kramer, R.E., DuBois, R.N., Simpson, E.R., Anderson, C.M., Kashiwagi, K., Lambeth, J.D., Jefcoate, C.R. and Waterman, M.R. (1982) "Cell-Free Synthesis of Precursor Forms of Mitochondrial Steroid Hydroxylase Enzymes of the Bovine Adrenal Cortex" Arch. Biochem. Biophys. 215, 478-485.
Lambeth, J.D., Kitchen, S.E., Farooqui, A., Tuckey, R. and Kamin, H. (1982) "Cytochrome P-450-Substrate Interactions: Binding and Catalytic Activity Using Hydroxycholesterols." J. Biol. Chem. 257, 1876-1884.
Lambeth, J.D. (1981) "Cytochrome P-450scc: Cardiolipin as an Effector of Activity of a Mitochondrial Cytochrome P-450." J. Biol. Chem. 256, 4757-4762.
DuBois, R., Simpson, E.R., Tuckey, J., Lambeth, J.D., and Waterman, M.R. (1981) "Induction of Cytochrome P-450scc by ACTH in Cultured Adult Bovine Adrenal Cells: Evidence for a Higher Molecular Weight Precursor Form of This Enzyme." Proc. Nat. Acad. Sci. 78, 1028-1032.
Lambeth, J.D., Lancaster, J.D. and Kamin, H. (1981) "Steroidogenic Electron Transport by Adrenodoxin Reductase and Adrenodoxin: Use of the Acetylated Cytochrome c as a Mechanistic Probe of Electron Transfer." J. Biol. Chem. 256, 3674-3678.
Merrill, A., Edmondson, D.E., Lambeth, J.D. and McCormick, D.B. (1981) "Formation and Mode of Action of Flavoproteins." Ann. Rev. Nutrition 1, 281-317.
Lambeth, J.D., Seybert, D. and Kamin, H. (1980) "Adrenodoxin Reductase-Adrenodoxin Complex: Rapid Formation and Breakdown of the Complex and a Slow Conformational Change in the Flavoprotein." J. Biol. Chem. 255, 4667-4672.
Lambeth, J.D., Seybert, D.W. and Kamin, H. (1980) "Phospholipid Vesicle-Reconstituted Cytochrome P-450scc: Mutually-Facilitated Binding of Cholesterol and Adrenodoxin." J. Biol. Chem. 255, 138-143.
Hall, C.L. and Lambeth, J.D. (1980) "Electron Transferring Flavoprotein: Role of the Anionic Flavosemiquinone." J. Biol. Chem. 255, 3591-3595.
Lambeth, J.D., Kamin, H. and Seybert, D.W. (1980) "Phospholipid Vesicle Reconstituted Cytochrome P-450scc: Role of the Membrane in Control of Activity and Spin State of the Cytochrome." J. Biol. Chem. 255, 8282-8288.
Hall, C.L., Lambeth, J.D. and Kamin, H. (1979) "Acyl CoA Complexes of General Acyl CoA Dehydrogenase and Electron-Transfer Flavoprotein." J. Biol. Chem. 254, 2023-2031.
Seybert, D., Lancaster, J., Lambeth, J.D. and Kamin, H. (1979) "Participation of the Membrane in the Side Chain Cleavage of Cholesterol: Reconstitution of Cytochrome P-450scc Into Phospholipid Vesicles." J. Biol. Chem. 254, 12088-12098.
Lambeth, J.D. and Kamin, H. (1979) "Adrenodoxin Reductase-Adrenodoxin Complex: Rate-Limiting Step in NADPH-Cytochrome c Reduction." J. Biol. Chem. 254, 2766-2774.
Lambeth, J.D., Seybert, D. and Kamin, H. (1979) "Ionic Effects on Adrenal Steroidogenic Electron Transport: The Role of Adrenodoxin as an Electron Shuttle." J. Biol. Chem. 254, 7255-7264.
Seybert, D., Lambeth, J.D. and Kamin, H. (1978) "Participation of a Second Adrenodoxin in Adrenal Cortex Mitochondrial Steroid Hydroxylations." J. Biol. Chem. 253, 8355-8385.
Lambeth, J.D. and Kamin, H. (1977) "Adrenodoxin Reductase and Adrenodoxin: The Mechanisms of Reduction of Ferricyanide and Cytochrome c." J. Biol. Chem. 252, 2908-2917.
Lambeth, J.D., and Kamin, H. (1976) "Adrenodoxin Reductase: Properties of the Complexes of Reduced Enzyme with NADP+ and NADPH." J. Biol. Chem. 251, 4299-4306.
Lambeth, J.D., McCaslin, D.R. and Kamin, H. (1976) "Adrenodoxin Reductase-Adrenodoxin Complex: Catalytic and Thermodynamic Properties." J. Biol. Chem. 251, 7545-7550.
Estabrook, R.W., Mason, J.I., Baron, J., Lambeth, D. and Waterman, M. (1972) "Drugs, Alcohol and Sex Hormones: A Molecular Perspective of the Receptivity of Cytochrome P-450" Ann. N.Y. Acad. Sci. 212, 27-49.