RONALD N contact HINES

Summary

Affiliation: Medical College of Wisconsin
Country: USA

Publications

  1. doi Developmental expression of drug metabolizing enzymes: impact on disposition in neonates and young children
    R N Hines
    Department of Pediatrics, Medical College of Wisconsin and Children s Research Institute, Children s Hospital and Health Systems, 8701 Watertown Plank Rd, Milwaukee, WI 53226, USA
    Int J Pharm 452:3-7. 2013
  2. ncbi Molecular regulation of genes encoding xenobiotic-metabolizing enzymes: mechanisms involving endogenous factors
    R N Hines
    Department of Pediatrics, Birth Defects Research Center, Medical College of Wisconsin, 8701 Watertown Plank Rd, Milwaukee, WI 53226 4801, USA
    Drug Metab Dispos 29:623-33. 2001
  3. ncbi Ontogeny of human hepatic cytochromes P450
    Ronald N Hines
    Department of Pediatrics, Medical College of Wisconsin, Children s Hospital and Health Systems, Milwaukee, WI 53226 4801, USA
    J Biochem Mol Toxicol 21:169-75. 2007
  4. doi The ontogeny of drug metabolism enzymes and implications for adverse drug events
    Ronald N Hines
    Department of Pediatrics, Medical College of Wisconsin, and Children s Research Institute, Children s Hospital and Health Systems, Milwaukee, WI 53226 4801, USA
    Pharmacol Ther 118:250-67. 2008
  5. ncbi Regulatory polymorphisms and their contribution to interindividual differences in the expression of enzymes influencing drug and toxicant disposition
    Ronald N Hines
    Department of Pediatrics, Medical College of Wisconsin, Milwaukee, Wisconsin 53226, USA
    Drug Metab Rev 40:263-301. 2008
  6. ncbi The ontogeny of human drug-metabolizing enzymes: phase I oxidative enzymes
    Ronald N Hines
    Birth Defects Research Center, Department of Pediatrics, Medical College of Wisconsin and Children s Hospital of Wisconsin, Milwaukee, Wisconsin 53226 4801, USA
    J Pharmacol Exp Ther 300:355-60. 2002
  7. ncbi Human hepatic flavin-containing monooxygenases 1 (FMO1) and 3 (FMO3) developmental expression
    Sevasti B Koukouritaki
    Department of Pediatrics, Birth Defects Research Center, Medical College of Wisconsin, Milwaukee, Wisconsin 53226, USA
    Pediatr Res 51:236-43. 2002
  8. doi Differential regulation of human hepatic flavin containing monooxygenase 3 (FMO3) by CCAAT/enhancer-binding protein beta (C/EBPbeta) liver inhibitory and liver activating proteins
    David E Klick
    Department of Pediatrics and Pharmacology, Medical College of Wisconsin and Children s Hospital and Health System, Milwaukee, WI 53226, USA
    Biochem Pharmacol 76:268-78. 2008
  9. ncbi Identification and functional analysis of a novel human CYP2E1 far upstream enhancer
    Jeff D Shadley
    Clinical Pharmacology, Pharmacogenetics and Teratology, Department of Pediatrics, Medical College of Wisconsin, Milwaukee, Wisconsin 53226 4801, USA
    Mol Pharmacol 71:1630-9. 2007
  10. ncbi Developmental and tissue-specific expression of human flavin-containing monooxygenases 1 and 3
    Ronald N Hines
    Medical College of Wisconsin, Department of Pediatrics, Milwaukee WI 53226, USA
    Expert Opin Drug Metab Toxicol 2:41-9. 2006

Research Grants

  1. Regulation of Drug Metabolizing Enzyme Ontogeny
    Ronald N Hines; Fiscal Year: 2010
  2. Regulation of Drug Metabolizing Enzyme Ontogeny
    RONALD HINES; Fiscal Year: 2009
  3. REGULATION OF FLAVIN MONOOXYGENASE GENE EXPRESSION
    RONALD HINES; Fiscal Year: 2003
  4. MECHANISMS OF TOXICITY GORDON CONFERENCE
    RONALD HINES; Fiscal Year: 2002
  5. Warfarin Pharmacogenetics in Pediatric Patients
    RONALD N contact HINES; Fiscal Year: 2010

Collaborators

Detail Information

Publications42

  1. doi Developmental expression of drug metabolizing enzymes: impact on disposition in neonates and young children
    R N Hines
    Department of Pediatrics, Medical College of Wisconsin and Children s Research Institute, Children s Hospital and Health Systems, 8701 Watertown Plank Rd, Milwaukee, WI 53226, USA
    Int J Pharm 452:3-7. 2013
    ..Such models have proven useful in predicting the range of expected metabolic capacities at a given age. ..
  2. ncbi Molecular regulation of genes encoding xenobiotic-metabolizing enzymes: mechanisms involving endogenous factors
    R N Hines
    Department of Pediatrics, Birth Defects Research Center, Medical College of Wisconsin, 8701 Watertown Plank Rd, Milwaukee, WI 53226 4801, USA
    Drug Metab Dispos 29:623-33. 2001
    ....
  3. ncbi Ontogeny of human hepatic cytochromes P450
    Ronald N Hines
    Department of Pediatrics, Medical College of Wisconsin, Children s Hospital and Health Systems, Milwaukee, WI 53226 4801, USA
    J Biochem Mol Toxicol 21:169-75. 2007
    ....
  4. doi The ontogeny of drug metabolism enzymes and implications for adverse drug events
    Ronald N Hines
    Department of Pediatrics, Medical College of Wisconsin, and Children s Research Institute, Children s Hospital and Health Systems, Milwaukee, WI 53226 4801, USA
    Pharmacol Ther 118:250-67. 2008
    ..Common themes emerging from our current knowledge also will be discussed. Finally, the review will highlight gaps in knowledge that will be important to advance this field...
  5. ncbi Regulatory polymorphisms and their contribution to interindividual differences in the expression of enzymes influencing drug and toxicant disposition
    Ronald N Hines
    Department of Pediatrics, Medical College of Wisconsin, Milwaukee, Wisconsin 53226, USA
    Drug Metab Rev 40:263-301. 2008
    ..Our current understanding of regulatory polymorphisms impacting drug disposition is reviewed including specific discussion regarding knowledge gaps and future research opportunities...
  6. ncbi The ontogeny of human drug-metabolizing enzymes: phase I oxidative enzymes
    Ronald N Hines
    Birth Defects Research Center, Department of Pediatrics, Medical College of Wisconsin and Children s Hospital of Wisconsin, Milwaukee, Wisconsin 53226 4801, USA
    J Pharmacol Exp Ther 300:355-60. 2002
    ..However, with few exceptions, complete temporal relationship information during development is not known. Furthermore, most studies have concentrated on hepatic expression and much less is known about extrahepatic developmental events...
  7. ncbi Human hepatic flavin-containing monooxygenases 1 (FMO1) and 3 (FMO3) developmental expression
    Sevasti B Koukouritaki
    Department of Pediatrics, Birth Defects Research Center, Medical College of Wisconsin, Milwaukee, Wisconsin 53226, USA
    Pediatr Res 51:236-43. 2002
    ..9 +/- 8.6 pmol/mg protein). Finally, 2- to 20-fold interindividual variation in FMO1 and FMO3 protein levels were observed, depending on the age bracket...
  8. doi Differential regulation of human hepatic flavin containing monooxygenase 3 (FMO3) by CCAAT/enhancer-binding protein beta (C/EBPbeta) liver inhibitory and liver activating proteins
    David E Klick
    Department of Pediatrics and Pharmacology, Medical College of Wisconsin and Children s Hospital and Health System, Milwaukee, WI 53226, USA
    Biochem Pharmacol 76:268-78. 2008
    ..Chromatin immunoprecipitation demonstrated C/EBPbeta binding to the FMO3 domain I element in intact cells and adult liver tissue. These results are consistent with C/EBPbeta being important for regulating hepatic FMO3 expression...
  9. ncbi Identification and functional analysis of a novel human CYP2E1 far upstream enhancer
    Jeff D Shadley
    Clinical Pharmacology, Pharmacogenetics and Teratology, Department of Pediatrics, Medical College of Wisconsin, Milwaukee, Wisconsin 53226 4801, USA
    Mol Pharmacol 71:1630-9. 2007
    ..The enhancer sequence is conserved within the human population but seems species-specific. The identification of this novel enhancer and its putative mechanism adds to the complexities of human CYP2E1 regulation...
  10. ncbi Developmental and tissue-specific expression of human flavin-containing monooxygenases 1 and 3
    Ronald N Hines
    Medical College of Wisconsin, Department of Pediatrics, Milwaukee WI 53226, USA
    Expert Opin Drug Metab Toxicol 2:41-9. 2006
    ..Because it is so closely related, tissue-specific expression patterns also are examined. Finally, a summary of what is known in animal models is presented as a point of comparison...
  11. ncbi Molecular mechanisms regulating human CYP4B1 lung-selective expression
    Mark T Poch
    Department of Pediatrics, Medical College of Wisconsin, 8701 Watertown Plank Rd, Milwaukee, WI 53226, USA
    Drug Metab Dispos 33:1174-84. 2005
    ..Thus, the composite findings are consistent with both the proximal Sp1 elements and the distal regulatory element acting to synergistically control CYP4B1 lung-selective expression...
  12. ncbi Trichloroethylene decreases heat shock protein 90 interactions with endothelial nitric oxide synthase: implications for endothelial cell proliferation
    Jingsong Ou
    Department of Surgery, Division of Pediatric Surgery, Cardiovascular Center, Milwaukee, Wisconsin 53226, USA
    Toxicol Sci 73:90-7. 2003
    ..Such changes in endothelial function may play an important role in the development of congenital heart defects...
  13. ncbi Developmental expression of human hepatic CYP2C9 and CYP2C19
    Sevasti B Koukouritaki
    Department of Pediatrics, Medical College of Wisconsin, Milwaukee, WI 53226 4801, USA
    J Pharmacol Exp Ther 308:965-74. 2004
    ..The ontogeny of CYP2C9 and -2C19 were dissimilar among both fetal and 0- to 5-months postnatal samples, implying different developmental regulatory mechanisms...
  14. ncbi Publication of stand-alone single nucleotide polymorphism (SNP) discovery data
    Ronald N Hines
    Medical College of Wisconsin, Department of Pediatrics, Birth Defects Research Center, Milwaukee, WI 53226, USA
    Drug Metab Dispos 31:1073. 2003
  15. ncbi Alternative processing of the human FMO6 gene renders transcripts incapable of encoding a functional flavin-containing monooxygenase
    Ronald N Hines
    Department of Pediatrics, Birth Defects Research Center, Medical College of Wisconsin, Milwaukee, Wisconsin 53226 4801, USA
    Mol Pharmacol 62:320-5. 2002
    ....
  16. ncbi Genetic variability at the human FMO1 locus: significance of a basal promoter yin yang 1 element polymorphism (FMO1*6)
    Ronald N Hines
    Department of Pediatrics, Birth Defects Research Center, Medical College of Wisconsin, Milwaukee WI 53226 4801, USA
    J Pharmacol Exp Ther 306:1210-8. 2003
    ..Thus, the FMO1*6 variant may account for some of the observed interindividual variation in FMO1 expression...
  17. ncbi Mechanisms regulating human FMO3 transcription
    David E Klick
    Department of Pediatrics, and the Children s Research Institute, Medical College of Wisconsin, and Children s Hospital and Health System, Milwaukee, Wisconsin 53226, USA
    Drug Metab Rev 39:419-42. 2007
    ....
  18. ncbi Two distinct classes of CCAAT box elements that bind nuclear factor-Y/alpha-actinin-4: potential role in human CYP1A1 regulation
    Mark T Poch
    Birth Defects Research Center, Department of Pediatrics, Medical College of Wisconsin, Milwaukee 53226, USA
    Toxicol Appl Pharmacol 199:239-50. 2004
    ....
  19. ncbi The ontogeny of human drug-metabolizing enzymes: phase II conjugation enzymes and regulatory mechanisms
    D Gail McCarver
    Birth Defects Research Center, Department of Pediatrics, Medical College of Wisconsin and Children s Hospital of Wisconsin, Milwaukee, Wisconsin 53226 4801, USA
    J Pharmacol Exp Ther 300:361-6. 2002
    ..There is a paucity of data regarding mechanisms for the onset of extrahepatic fetal expression or specific mechanisms determining temporal switches, such as those observed within the CYP3A and flavin-containing monooxygenase families...
  20. ncbi Flavin-containing monooxygenase genetic polymorphism: impact on chemical metabolism and drug development
    Sevasti B Koukouritaki
    Medical College of Wisconsin, Department of Pediatrics, Clinical Pharmacology, Pharmacogenetics and Teratology Section, 8701 Watertown Plank Rd, Milwaukee, Wisconsin 53226, USA
    Pharmacogenomics 6:807-22. 2005
    ..Thus, it is anticipated that knowledge regarding functionally-relevant FMO genetic variability will become increasingly important for making drug development and patient therapeutic choices...
  21. ncbi Human hepatic CYP2E1 expression during development
    Elizabeth K Johnsrud
    Birth Defects Research Center, Department of Pediatrics, Medical College of Wisconsin, Milwaukee, WI 53226, USA
    J Pharmacol Exp Ther 307:402-7. 2003
    ..Furthermore, the postnatal data suggest that infants less than 90 days old would have decreased clearance of CYP2E1 substrates compared with older infants, children, and adults...
  22. pmc Discovery of novel flavin-containing monooxygenase 3 (FMO3) single nucleotide polymorphisms and functional analysis of upstream haplotype variants
    Sevasti B Koukouritaki
    Department of Pediatrics, Medical College of Wisconsin, 8701 Watertown Plank Rd, Milwaukee, WI 53226, USA
    Mol Pharmacol 68:383-92. 2005
    ..In conclusion, FMO3 promoter haplotype variants modulate gene function and probably contribute to interindividual differences in FMO3 expression...
  23. pmc Novel CYP2C9 promoter variants and assessment of their impact on gene expression
    Melissa A Kramer
    Department of Pediatrics, Medical College of Wisconsin, Milwaukee WI 53226, USA
    Mol Pharmacol 73:1751-60. 2008
    ..These data suggest that genetic variation within CYP2C9 regulatory sequences is likely to contribute to differences in CYP2C9 phenotype both within and among different populations...
  24. ncbi Identification and functional analysis of common human flavin-containing monooxygenase 3 genetic variants
    Sevasti B Koukouritaki
    Department of Pediatrics, Medical College of Wisconsin, 8701 Watertown Plank Rd, Milwaukee, WI 53226, USA
    J Pharmacol Exp Ther 320:266-73. 2007
    ....
  25. ncbi Population-based analysis of methadone distribution and metabolism using an age-dependent physiologically based pharmacokinetic model
    Feng Yang
    Department of Physiology, Medical College of Wisconsin, Biotechnology and Bioengineering Center, Milwaukee, WI 53226, USA
    J Pharmacokinet Pharmacodyn 33:485-518. 2006
    ..In addition, it is shown that when doses are designed for individuals based on prior protein expression information, inter-individual variability in methadone kinetics may be greatly reduced...
  26. pmc Approaches for assessing risks to sensitive populations: lessons learned from evaluating risks in the pediatric population
    Ronald N Hines
    Medical College of Wisconsin, Department of Pediatrics, Children s Research Institute, Children s Hospital and Health Systems, Milwaukee, Wisconsin 53226 4801, USA
    Toxicol Sci 113:4-26. 2010
    ..Recommendations as to future research needs and/or alternate methodological considerations are also made...
  27. ncbi Pharmacogenomics and the future of drug therapy
    Ronald N Hines
    Department of Pediatrics, Section of Clinical Pharmacology, Pharmacogenetics and Teratology, Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, WI 53226, USA
    Pediatr Clin North Am 53:591-619. 2006
    ..Finally, a discussion of future promises and challenges to the application of pharmacogenomics is presented, including economic and ethical issues...
  28. doi Developmental changes in human liver CYP2D6 expression
    Jeffrey C Stevens
    Pfizer Corporation, Global Research and Development, Chesterfield, Missouri, USA
    Drug Metab Dispos 36:1587-93. 2008
    ..These results suggest that age and genetic determinants of CYP2D6 expression constitute significant determinants of interindividual variability in CYP2D6-dependent metabolism during ontogeny...
  29. ncbi Characterization of the human lung CYP2F1 gene and identification of a novel lung-specific binding motif
    Brian A Carr
    Department of Pharmacology and Toxicology, University of Utah, 30 S 2000 E, Salt Lake City, UT 84112, USA
    J Biol Chem 278:15473-83. 2003
    ..These studies identified a novel LSF and its consensus sequence that may control tissue-specific expression of CYP2F1...
  30. ncbi Genotyping and site-directed mutagenesis of a cytochrome P450 meander Pro-X-Arg motif critical to CYP4B1 catalysis
    Yi Min Zheng
    Department of Medicinal Chemistry, University of Washington, Seattle, WA 98195, USA
    Toxicol Appl Pharmacol 186:119-26. 2003
    ..These data provide additional evidence for the importance of this meander region Pro-X-Arg motif in CYP4B1 heme binding and catalytic function...
  31. ncbi CYP2C9 exon 4 mutations and warfarin dose phenotype in Asians
    Allan E Rettie
    Blood 101:2896-7. 2003
  32. ncbi Developmental expression of the major human hepatic CYP3A enzymes
    Jeffrey C Stevens
    Pfizer Pharmacokinetics, Dynamics, and Metabolism, 301 Henrietta St, 7265 300 306, Kalamazoo, MI 49007, USA
    J Pharmacol Exp Ther 307:573-82. 2003
    ..Low CYP3A4 expression was noted for fetal liver (< or =10 pmol/mg), with mean levels increasing with postnatal age...
  33. ncbi Differences in FMO2*1 allelic frequency between Hispanics of Puerto Rican and Mexican descent
    Sharon K Krueger
    Department of Environmental and Molecular Toxicology, Oregon State University, Corvallis, Oregon 97331, USA
    Drug Metab Dispos 32:1337-40. 2004
    ..0066) that FMO2*1 is more common among Puerto Ricans (7%) than among individuals of Mexican descent (2%). The overall occurrence of FMO2*1 among Hispanics of all origins is estimated to be between 2 and 7%...
  34. ncbi Sp1 and Sp3 regulate basal transcription of the human CYP2F1 gene
    Jie Wan
    Department of Pharmacology and Toxicology, 30 South 2000 East, Room 201, University of Utah, Salt Lake City, UT 84112 5820
    Drug Metab Dispos 33:1244-53. 2005
    ..Thus, these studies demonstrated that four Sp1-dependent proximal promoter elements drive organ-selective CYP2F1 gene transcription, and that Sp1 and Sp3 factors interact to modulate constitutive CYP2F1 transcription in lung cells...
  35. pmc Haplotype and functional analysis of four flavin-containing monooxygenase isoform 2 (FMO2) polymorphisms in Hispanics
    Sharon K Krueger
    Department of Environmental and Molecular Toxicology, Oregon State University, Corvallis, OR 97331, USA
    Pharmacogenet Genomics 15:245-56. 2005
    ..23,238C (p.Q472) and 124 previously genotyped as homozygous g.23,238 T (p.X472); (2) determine FMO2 haplotypes in this population; and (3) assess the functional impact of SNPs in expressed proteins...
  36. ncbi Biochemical and clinical aspects of the human flavin-containing monooxygenase form 3 (FMO3) related to trimethylaminuria
    John R Cashman
    Human BioMolecular Research Institute, San Diego, CA, USA
    Curr Drug Metab 4:151-70. 2003
    ..The remarkable progress in the biochemical, genetic, clinical basis for understanding the trimethylaminuria condition is summarized and points to needs in the treatment of individuals suffering from trimethylaminuria...
  37. ncbi Genetic polymorphisms of flavin-containing monooxygenase (FMO)
    Sharon K Krueger
    Department of Environmental and Molecular Toxicology and The Linus Pauling Institute, Oregon State University, Corvallis, USA
    Drug Metab Rev 34:523-32. 2002
    ..Polymorphic expression of functional FMO2 in the individuals of African and Hispanic descent may markedly influence drug metabolism and/or xenobiotic toxicity in the lung...
  38. ncbi Developmental expression of aryl, estrogen, and hydroxysteroid sulfotransferases in pre- and postnatal human liver
    Zhengbo Duanmu
    Institute of Environmental Health Sciences, Wayne State University, 2727 Second Avenue, Room 4000, Detroit, MI 48201, USA
    J Pharmacol Exp Ther 316:1310-7. 2006
    ....
  39. ncbi The role of flavin-containing monooxygenase (FMO) in the metabolism of tamoxifen and other tertiary amines
    Sharon K Krueger
    Department of Environmental and Molecular Toxicology, The Linus Pauling Institute, Oregon State University, Corvallis, 97331, USA
    Drug Metab Rev 38:139-47. 2006
    ..We collaborated with Dr. Kupfer's laboratory and recently determined that the low level of tamoxifen N-oxide production in human liver microsomes may be explained by the kinetics of FMO1 versus FMO3...
  40. ncbi Enzyme-mediated protein haptenation of dapsone and sulfamethoxazole in human keratinocytes: II. Expression and role of flavin-containing monooxygenases and peroxidases
    Piyush M Vyas
    Division of Pharmaceutics, College of Pharmacy, University of Iowa, Iowa City, Iowa, USA
    J Pharmacol Exp Ther 319:497-505. 2006
    ..Thus, our results suggest an important role for FMO3 and yet-to-be identified peroxidases in the bioactivation of sulfonamides in NHEKs...
  41. ncbi Genetics and susceptibility to toxic chemicals: do you (or should you) know your genetic profile?
    Lawrence H Lash
    Department of Pharmacology, Wayne State University School of Medicine, 540 East Canfield Avenue, Detroit, Michigan 48201, USA
    J Pharmacol Exp Ther 305:403-9. 2003
    ..Finally, ethical and legal concerns with the application of this knowledge and methodology to human health will be discussed...
  42. ncbi Enzyme-mediated protein haptenation of dapsone and sulfamethoxazole in human keratinocytes: I. Expression and role of cytochromes P450
    Piyush M Vyas
    Division of Pharmaceutics, College of Pharmacy, University of Iowa, Iowa City, Iowa, USA
    J Pharmacol Exp Ther 319:488-96. 2006
    ....

Research Grants12

  1. Regulation of Drug Metabolizing Enzyme Ontogeny
    Ronald N Hines; Fiscal Year: 2010
    ..This knowledge will be invaluable in modifying risk policies to minimize/avoid adverse drug events and toxicity due to environmental exposures in children. ..
  2. Regulation of Drug Metabolizing Enzyme Ontogeny
    RONALD HINES; Fiscal Year: 2009
    ..This knowledge will be invaluable in modifying risk policies to minimize/avoid adverse drug events and toxicity due to environmental exposures in children. ..
  3. REGULATION OF FLAVIN MONOOXYGENASE GENE EXPRESSION
    RONALD HINES; Fiscal Year: 2003
    ..It will be critical for the future rationale design of drugs and therapeutic regimens, as well as for the development of prevention/intervention strategies for at risk individuals or populations. ..
  4. MECHANISMS OF TOXICITY GORDON CONFERENCE
    RONALD HINES; Fiscal Year: 2002
    ..There also is substantial involvement of new personnel as Chairs and co-Chairs. Thus, the Mechanism of Toxicity GRC is poised to continue its growth as the single leading small conference on Molecular Toxicology. ..
  5. Warfarin Pharmacogenetics in Pediatric Patients
    RONALD N contact HINES; Fiscal Year: 2010
    ..The IWPC clearly stated that additional research was needed with respect to the development of a similar algorithm for children and young adults. The proposed research will fill this important knowledge gap. ..