Joseph L Napoli

Professor, Chair of Nutritional Science and Toxicology Department, Chair Graduate Group in Nutrition
Ph.D.  Medicinal Chemistry    University of Michigan, 1975
  

115 Morgan Hall #3104
Berkeley, California 94720-3104
jna@berkeley.edu
office: 510-642-2502   lab: 510-643-0460   fax:  510-642-0535

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Metabolism of retinol (vitamin A) produces the endocrine factor retinoic acid (RA). RA controls the differentiation programs of epithelial cells in the digestive tract, the respiratory system, skin, bone, the nervous system and the immune system. RA also promotes growth, reproduction (fertility, placental development, embryonic development), and resistance to and recovery from infection. The embryo requires RA soon after conception and the requirement continues throughout the lifespan of vertebrates. Synthetic analogs of RA produce remission of skin diseases (such as severe cystic acne, psoriasis, and photoaging), augment treatment of diabetes, and function as cancer chemopreventive agents. RA acts by controlling gene transcription through transcription factors in the superfamily of nuclear hormone receptors. The dynamic and interrelated spatial-temporal expression of RA receptors, retinol and RA-specific binding proteins, and enzymes of RA homeostasis constitute a unique endocrine system, obligatory for all vertebrate life.

This lab has ongoing projects directed to understanding metabolic control mechanisms of RA homeostasis and their impact on vitamin A function in mammals. Projects rely on techniques of molecular biology (genomic and cDNA cloning, polymerase chain reaction, analyses of mRNA expression), genetic manipulation (knock-out mice), protein chemistry (heterologous expression and purification, protein-protein interaction), enzyme kinetics, and bioimaging (in situ hybridization, immunocytochemistry). Targeted areas include function of RA in the testis during spermatogenesis, the contribution of retinoid-metabolizing enzymes to embryonic development, and retinoid endocrinology in the nervous system, the mammary gland, adrenal and prostate. Interactions between androgens and retinoids also are investigated. The goals are to understand, at the molecular level, endocrine and dietary regulation of RA homeostasis during development, disease and aging.

Kane MA, Chen N, Sparks S, Napoli JL. Quantification of endogenous retinoic acid in limited biological samples by LC/MS/MS. Biochem J. 2005 May 15;388(Pt 1):363-9.

McCaffery P, Koul O, Smith D, Napoli JL, Chen N, Ullman MD. Ethanol increases retinoic acid production in cerebellar astrocytes and in cerebellum. Brain Res Dev Brain Res. 2004 Nov 25;153(2):233-41

Zhang M, Hu P, Napoli JL. Elements in the N-terminal signaling sequence that determine cytosolic topology of short-chain dehydrogenases/reductases. Studies with retinol dehydrogenase type 1 and cis-retinol/androgen dehydrogenase type 1. J Biol Chem. 2004 Dec 3;279(49):51482-9. Epub 2004 Sep 7

M.-S. Song, W. Chen, M. Zhang and J.L. Napoli. Identification of a mouse short-chain dehydrogenase/reductase gene, RDH-S: function of non-catalytic amino acid residues in enzyme activity, J. Biol. Chem. 278, in press (2003). PDF

Z. Lei, W. Chen, M. Zhang and J.L. Napoli. Reduction of all-trans-retinal in the mouse liver peroxisome fraction by the short-chain dehydrogenase/reductase RRD: induction by the PPARa-ligand clofibrate, Biochemistry 42, 4190-4196 (2003). PDF

M. Lin, M. Zhang, M. Abraham, S.M. Smith and J.L. Napoli. Mouse RALDH4: molecular cloning, cellular expression, and activity in 9-cis-retinoic acid biosynthesis in intact cells, J. Biol. Chem. 278, 9856-9861 (2003). PDF

M. Zhang, B.C. Thomas, and J.L. Napoli (2003). Gene structure and minimal promoter of mouse rdh1, Gene 305, 121-131.

R. Zhuang, M. Lin, and J. L. Napoli, cis-Retinol/androgen dehydrogenase, isozyme 3 (CRAD3): a short-chain dehydrogenase active in a reconstituted path of 9-cis-retinoic acid biosynthesis in intact cells, Biochemistry 41, 3477-3483 (2002).PDF

Chen W, Song MS, Napoli JL. SDR-O: an orphan short-chain dehydrogenase/reductase localized at mouse chromosome 10/human chromosome 12. Gene. 2002 Jul 10;294(1-2):141-6

Chai X, Chen W, Napoli JL. Structure, promoter and chromosomal localization of rdh6. Gene. 2001 Aug 22;274(1-2):27-33

Wang J, Bongianni JK, Napoli JL. The N-terminus of retinol dehydrogenase type 1 signals cytosolic orientation in the microsomal membrane. Biochemistry. 2001 Oct 23;40(42):12533-40

M. Zhang, W. Chen, S. M. Smith, and J. L. Napoli, Molecular characterization of a mouse short-chain dehydrogenase/reductase active with all-trans-retinol in intact cells: mRDH1. J. Biol. Chem. 276, 44083-44090 (2001).PDF

V. Chandrasekaran, Y. Zhai, M. Wagner, P.L. Kaplan, J.L. Napoli and D. Higgins.Retinoic acid regulates the morphological development of sympathetic neurons. J. Neurobiol. 42, 383-393 (2000).