Colin D. Funk received his doctoral training at McGill University, Montreal where he studied lipid and eicosanoid biochemistry. His postdoctoral training was with Bengt Samuelsson, 1982 Nobel Laureate, where he introduced molecular biology to the field of leukotrienes and related eicosanoids by the successful cloning and expression of 5- lipoxygenase and leukotriene A4 hydrolase genes. Presently, he is an Assistant Professor of Pharmacology (tenure track) in the Division of Clinical Pharmacology at Vanderbilt University. Dr. Funk's present research goals are to explore the structure and functions of the platelet 12-lipoxygenase (12LX) enzyme through the use of molecular biology techniques, including in vitro mutagenesis and chimeric enzyme expression strategies. The role of translocation in the activation of this enzyme will be considered in transfected cells and platelets. The regulation of expression of the 12LX gene will be investigated using a megakaryocytic/platelet cell model. The complementary DNA encoding a human 12LX isoform (non-platelet) will be isolated by polymerase chain reaction cloning and/or hybridization screening and finally the 12LX gene(s) will be cloned and chromosomal localizations determined. Future research endeavors will focus on in vivo gene transfer and gene inactivation experiments to clarify the biological role of lipoxygenases in health and disease states, particularly in the realm of vascular homeostasis. The receipt of a Research Career Development Award will enable him to focus entirely on pertinent, rapidly-developing areas in the eicosanoid field where he is an acknowledged expert. The institute is committed to Dr. Funk's development as an independent investigator. The protection of his time afforded by the award of an RCDA will further this goal.

National Institute of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
Modified Research Career Development Award (K04)
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Hematology Subcommittee 2 (HEM)
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Vanderbilt University Medical Center
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United States
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Sun, D; Funk, C D (1996) Disruption of 12/15-lipoxygenase expression in peritoneal macrophages. Enhanced utilization of the 5-lipoxygenase pathway and diminished oxidation of low density lipoprotein. J Biol Chem 271:24055-62
Funk, C D (1996) The molecular biology of mammalian lipoxygenases and the quest for eicosanoid functions using lipoxygenase-deficient mice. Biochim Biophys Acta 1304:65-84
Chen, X S; Naumann, T A; Kurre, U et al. (1995) cDNA cloning, expression, mutagenesis, intracellular localization, and gene chromosomal assignment of mouse 5-lipoxygenase. J Biol Chem 270:17993-9
Funk, C D; Chen, X S; Kurre, U et al. (1995) Leukotriene-deficient mice generated by targeted disruption of the 5-lipoxygenase gene. Adv Prostaglandin Thromboxane Leukot Res 23:145-50
Chen, X S; Kurre, U; Jenkins, N A et al. (1994) cDNA cloning, expression, mutagenesis of C-terminal isoleucine, genomic structure, and chromosomal localizations of murine 12-lipoxygenases. J Biol Chem 269:13979-87
Kuchinke, W; Funk, C D (1994) Fibronectin-induced cell spreading and down-regulation of 12-lipoxygenase expression in megakaryocytic DAMI cells. Biochem Biophys Res Commun 204:606-12
Funk, C D; Kurre, U; Griffis, G (1994) Targeted gene disruption by homologous recombination. Toward an understanding of specific blood cell functions. Ann N Y Acad Sci 714:253-8
Romano, M; Chen, X S; Takahashi, Y et al. (1993) Lipoxin synthase activity of human platelet 12-lipoxygenase. Biochem J 296 ( Pt 1):127-33
Funk, C D (1993) Molecular biology in the eicosanoid field. Prog Nucleic Acid Res Mol Biol 45:67-98
Chen, X S; Funk, C D (1993) Structure-function properties of human platelet 12-lipoxygenase: chimeric enzyme and in vitro mutagenesis studies. FASEB J 7:694-701

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