David Williams

david williams 

Department: EMT (473 Linus Pauling Science Center)
Director: Superfund Research Program
Ph.D. 1982 Oregon State University
Phone: 541-737-3277
Fax: 541-737-0497




My research interests are in the characterization and regulation of microsomal monooxygenase enzymes (Cytochromes P450 and Flavin-Containing Monooxygenases) active in drug metabolism and their involvement in the detoxication and/or bioactivation of drugs, xenobiotics and endogenous compounds. In addition, a major focus of current research efforts is on diet and cancer.  These studies employ both trout, mouse and human cell culture models to address mechanistic questions.  Currently, we are working on a model that addresses the issue of maternal diet on cancer risk for the fetus in later life.  I am an Investigator in The Linus Pauling Institute and the Marine and Freshwater Biomedical Sciences Center.




superfundDirector of the Superfund Research Program

Principal Investigator; Co-Investigator for Project 1 - PAHs in Humans at Environmental Levels: Pharmacokinetics, Metabolism and Susceptible Individuals

The focus of this project is on PAH-dependent cancers of skin in adults and transplacentally, lung, liver and lymphoid tissue and the potential for chemoprevention in reducing PAH-dependent cancer mortality.









Selected Publications:

  • Wang, R., Dashwood, W.-M., Löhr, C., Fischer, K., Nakagama, H., Williams, D. and Dashwood, R. (2008)  Beta-Catenin is Strongly Elevated in Rat Colonic Epithelium Following Short-Term Intermittent Treatment with 2-Amino-1-Methyl-6-Phenyimidazo[4,5-b]Pyridine (PhIP) and a High-Fat Diet. Cancer Sci., in press.
  • Tilton, S.C., Orner, G.A., Benninghoff, A.D., Carpenter, H.M., Hendricks, J.D., Pereira, C.B. and Williams, D.E. (2008)  Genomic Profiling Reveals an Alternate Mechanism for Hepatic Tumor Promotion by Perfluorooctanoic Acid in Rainbow Trout.  Environm. Hlth. Perspect., in press.
  • Castro, D.J., Yu, Z., Dashwood, R.H., Bailey, G.S., Baird, W.M. and Williams, D.E. (2008) A Model for the Study of Maternal Dietary Inhibition of Transplacental Carcinogenesis. In Recent Advances in Carcinogenesis, (R.M. Mohan, Ed.)
  • Castro, D.J., Yu., Z., Löhr, C.V., Pereira, C.B., Giovanini, J., Fischer, K.A., Orner, G.A., Dashwood, R.H., and Williams, D.E.  (2008)  Chemoprevention of Dibenzo[a,l]pyrene Transplacental Carcinogenesis in Mice Born to Mothers Administered Green Tea: Primary Role of Caffeine. Carcinogenesis, in press.
  • Walter, R.B., Timmins, G.S., Tilton, S.C., Orner, G.O., Benninghoff, A.D., Bailey, G.S. and Williams, D.E. (2008)  Carcinogenesis Models: Focus on Xiphophorus and Rainbow Trout, In Oceans and Human Health: Risks and Remedies from the Seas, (P. Walsh, Ed.), Elsevier.
  • Williams, D.E.  (2008)  Bioactivation of Xenobiotics in Lung: Role of CYPs and FMOs. In Advances in Bioactivation Research, (A.A. Elfarra, ed.), pp. 347-372, Am. Assoc. Pharm. Sci.
  • Wang, R., Dashwood, W.M., Löhr, C.V., Fisher, K.A., Pereira, C.B., Louderback, M., Nakagama, H., Bailey, G.S., Williams, D.E. and Dashwood, R.H.  (2008) Protective Versus Promotional Effects of White Tea and Caffeine on PhIP-Induced Tumorigenesis and β-Catenin Expression in the Rat.  Carcinogenesis 29:834-839.
  • Castro, D.J., Baird, W.M., Pereira, C., Giovanini, J., Löhr, C., Fischer, K., Yu, Z., Gonzalez, F.J., Krueger, S.K. and Williams, D.E. (2008) Fetal Cyp1b1 in Mice and Transplacental Carcinogenesis From Maternal Exposure to Dibenzo[a,l]pyrene. Cancer Prev. Res., Published Online First on March 19, 2008 as 10.1158/1940-6207.CAPR-07-0004.
  • Siddens, L.K., Henderson, M.C., VanDyke, J.E., Williams, D.E. and Krueger, S.K.  (2008)  Characterization of Mouse Flavin-Containing Monooxygenase Transcript Levels in Lung and Liver, and Activity of Expressed Isoforms.  Biochem. Pharmacol. 75:750-759.
  • Benninghoff, A.D. and Williams, D.E. (2008) Identification of a Transcriptional Fingerprint of Estrogen Exposure in Rainbow Trout Liver.  Toxicol. Sci. 101:65-80.
  • Simonich, M.T., McQuistan, T., Jubert, C., Pereira, C., Hendricks, J.D., Schimerlik, M., Zhu, B., Dashwood, R., Williams, D.E. and Bailey, G.S.  (2008)  Low-Dose Dietary Chlorophyll Inhibits Multi-Organ Carcinogenesis in the Rainbow Trout.  Fd. Chem. Toxicol, 46:1014-1024.
  • Carter, O., Dashwood, R.H., Wang, R., Dashwood, W.M., Orner, G.A., Fisher, K.A., Löhr, C.V., Pereira, C.B., Bailey, G.S. and Williams, D.E.  (2007) Comparison of White Tea, Green Tea, Epigallocatechin-3-Gallate and Caffeine as Inhibitors of PhIP-Induced Colonic Aberrant Crypts.  Nutr. Cancer 58:60-65.
  • Tilton, S.C., Hendricks, J.D., Orner, G.A., Pereira, C.B., Bailey, G.S. and Williams, D.E.  (2007)  Gene Expression Analysis During Tumor Enhancement by the Dietary Phytochemical and Supplement, 3,3’-Diindolylmethane, in Rainbow Trout.  Carcinogenesis, 28:1589-1598.
  • Simonich, M.T., Egner, P.A., Robuck, B.D., Orner, O., Jubert, C., Pereira, C., Groopman, J.D., Kensler, T.W., Dashwood, R.H., Williams, D.E. and Bailey, G.S. (2007)  Natural Chlorophyll Inhibits Aflatoxin B1 Induced Multi-Organ Carcinogenesis in the Rat.  Carcinogenesis 28:1294-1302..
  • Higdon, J.V., Delage, B., Williams, D.E. and Dashwood, R.H.  (2007)  Cruciferous Vegetables and Human Cancer Risk: Epidemiologic Evidence and Mechanistic Basis. Pharmacol. Res.55:224-236.
  • Koukouritaki, S.B., Poch, M.T., Henderson, M.C., Siddens, L.K., Krueger, S.K., VanDyke, J.E., Williams, D.E., Pajewski, N.M., Wang, T. and Hines, R.N.  (2007)  Identification and Functional Analysis of Common Human Flavin-Containing Monooxygenase 3 (FMO3) Genetic Variants. J. Pharmacol. Exptl. Therap. 320:266-273.
  • Wang, R., Dashwood, W.M., Bailey, G.S., Williams, D.E. and Dashwood, R.H.  (2006)  Tumors from Rats Given 1,2-Dimethylhydrazine Plus Chlorophyllin or Indole-3-Carbinol Contain Transcriptional Changes in β-Catenin that are Independent of β-Catenin Mutation Status.  Mutat. Res. 601:11-18.
  • Vyas, P.M., Roychowdhury, S., Koukouritaki, S.B., Hines, R.N., Krueger, S.K., Williams, D.E., Nauseef, W.M. and Svensson, C.K.  (2006)  Enzyme-Mediated Protein Haptenation of Dapsone and Sulfamethoxazole in Human Keratinocytes- II. Expression and Role of Flavin Monooxygenases and Peroxidases.  J. Pharmacol. Exptl. Therap. 319:497-505.
  • Yu, Z., Mahadevan, B., Lohr, C.V., Fischer, K.A., Louderback, M.A., Krueger, S.K., Pereira, C.B., Albershardt, D.J., Baird, W.M., Bailey, G.S. and Williams, D.E.  (2006)  Indole-3-Carbinol in the Maternal Diet Provides Chemoprotection for the Fetus Against Transplacental Carcinogenesis by the Polycyclic Aromatic Hydrocarbon, Dibenzo[a,l]pyrene.  Carcinogenesis 27:2116-2123.
  • Yu Z, Loehr CV, Fischer KA, Louderback MA, Krueger SK, Dashwood RH, Kerkvliet NI, Pereira CB, Jennings-Gee JE, Dance ST, Miller MS, Bailey GS, and Williams DE (2006) In utero exposure of mice to dibenzo[a,l]pyrene produces lymphoma in the offspring: role of the aryl hydrocarbon receptor. Cancer Res. 66(2):755-62.
  • Tilton, S.C., Givan, S.A., Pereira, C.B., Bailey, G.S., and Williams, D.E. (2005) Toxicogenomic Profiling of the Hepatic Tumor Promoters Indole-3-Carbinol, 17{beta}-estradiol and {beta}-naphthoflavone in Rainbow Trout. Toxicol Sci. [Epub ahead of print].
  • Tilton, S.C., Gerwick, L.G., Hendricks, J.D., Rosato, C.S., Corley-Smith, G., Givan, S.A., Bailey, G.S., Bayne, C.J., and Williams, D.E. (2005). Use of a rainbow trout oligonucleotide microarray to determine transcriptional patterns in aflatoxin B1-induced hepatocellular carcinoma compared to adjacent liver. Toxicol Sci. 88(2):319-30.
  • Krueger, S.K. and Williams, D.E. (2005) Mammalian Flavin-Containing Monooxygenases: Structure/Function, Genetic Polymorphisms and Role in Drug Metabolism. Pharmacol. Therap. 106:357-387.
  • Krueger, S.K., Siddens, L.K., Henderson, M.C., Andreasen, E.A., Tanguay, R.L., Pereira, C.B., Cabacungan, E.T., Hines, R.N., Ardlie, K. and Williams, D.E. (2005) Haplotype and Functional Analysis of Four Flavin-Containing Monooxygenase Isoform 2 (FMO2) Polymorphisms in Hispanics. Pharmacogenetics and Genomics. 15:245-256.
  • Traber, M.G., Siddens, L.K., Leonard, S.W., Schock, B., Gohil, K., Krueger, S.K., Cross, C.E. and Williams, D.E. (2005). Alpha-tocopherol modulates Cyp3a expression, increases gamma-CEHC production, and limits tissue gamma-tocopherol accumulation in mice fed high gamma-tocopherol diets. Free Rad. Biol. Med. 38:773-785.
  • Krueger, S.K., Siddens, L.K., Martin, S.R., Yu, A., Pereira, C.B., Cabacungan, E.T., Hines, R.N., Ardlie, K.G., Raucy, J.L. and Williams, D.E. (2004) Differences in FMO2*1 Allelic Frequency Between Hispanics of Puerto Rican and Mexican Descent. Drug Metabol. Dispos. 32:1337-1340.
  • Henderson, M.C., Krueger, S.K., Siddens, L.K, Stevens, J.F. and Williams, D.E. (2004) S-Oxygenation of the Thioether Organophosphate Insecticides Phorate and Disulfoton by Human Lung Flavin-Containing Monooxygenase 2. Biochem. Pharmacol. 68:959-967.
  • Henderson, M.C., Krueger, S.K., Stevens, J.F. and Williams, D.E. (2004) Human flavin-containing monooxygenase form 2 S-oxygenation: sulfenic acid formation from thioureas and oxidation of glutathione. Chem. Res. Toxicol. 17:633-640.
  • Mata, J.E., Yu, Z., Gray, J.E., Williams, D.E. and Rodriguez-Proteau, R. (2004) Effects of Chlorophyllin on Transport of Dibenzo(a,l)pyrene, 2 Amino-1-methyl-6-phenylimidazo-[4,5-b]pyridine, and Aflatoxin B1 across Caco-2 cell monolayers. Toxicology. 196:117-125.
  • William, D.E., Bailey, G.S., Reddy, A., Hendricks, J.D., Oganesian, A., Orner, G.A., Pereira, C.B., and Swenberg, J.A. (2003). The rainbow trout (Oncorhynchus mykiss) tumor model: recent applications in low-dose exposures to tumor initiators and promoters. Toxicol Pathol. 2003 Jan-Feb;31 Suppl:58-61.