Ivan Rusyn

Summary

Affiliation: University of North Carolina
Country: USA

Publications

  1. pmc FastMap: fast eQTL mapping in homozygous populations
    Daniel M Gatti
    Department of Environmental Sciences and Engineering, University of North Carolina, Chapel Hill, North Carolina 27599, USA
    Bioinformatics 25:482-9. 2009
  2. pmc Epigenetic alterations in liver of C57BL/6J mice after short-term inhalational exposure to 1,3-butadiene
    Igor Koturbash
    Division of Biochemical Toxicology, National Center for Toxicological Research, U S Food and Drug Administration, Jefferson, Arkansas, USA
    Environ Health Perspect 119:635-40. 2011
  3. pmc Mechanisms of HCV-induced liver cancer: what did we learn from in vitro and animal studies?
    Ivan Rusyn
    Department of Environmental Sciences and Engineering, University of North Carolina, Chapel Hill, NC 27599, USA Electronic address
    Cancer Lett 345:210-5. 2014
  4. pmc Trichloroethylene: Mechanistic, epidemiologic and other supporting evidence of carcinogenic hazard
    Ivan Rusyn
    University of North Carolina, Chapel Hill, NC, USA Electronic address
    Pharmacol Ther 141:55-68. 2014
  5. pmc Mechanistic considerations for human relevance of cancer hazard of di(2-ethylhexyl) phthalate
    Ivan Rusyn
    Department of Environmental Sciences and Engineering, University of North Carolina, Chapel Hill, NC 27599 7431, USA
    Mutat Res 750:141-58. 2012
  6. pmc Predictive modeling of chemical hazard by integrating numerical descriptors of chemical structures and short-term toxicity assay data
    Ivan Rusyn
    Department of Environmental Sciences and Engineering, University of North Carolina, Chapel Hill, North Carolina 27599, USA
    Toxicol Sci 127:1-9. 2012
  7. pmc Modes of action and species-specific effects of di-(2-ethylhexyl)phthalate in the liver
    Ivan Rusyn
    Department of Environmental Sciences and Engineering, School of Public Health, University of North Carolina, Chapel Hill, 27599 7431, USA
    Crit Rev Toxicol 36:459-79. 2006
  8. pmc Computational toxicology: realizing the promise of the toxicity testing in the 21st century
    Ivan Rusyn
    Department of Environmental Sciences and Engineering, School of Public Health, University of North Carolina Chapel Hill, Chapel Hill, North Carolina 27599 7431, USA
    Environ Health Perspect 118:1047-50. 2010
  9. ncbi request reprint Expression of base excision DNA repair genes is a sensitive biomarker for in vivo detection of chemical-induced chronic oxidative stress: identification of the molecular source of radicals responsible for DNA damage by peroxisome proliferators
    Ivan Rusyn
    Laboratory of Environmental Genomics, Department of Environmental Sciences and Engineering, University of North Carolina School of Public Health, Chapel Hill, North Carolina 27599, USA
    Cancer Res 64:1050-7. 2004
  10. pmc Systems biology and functional genomics approaches for the identification of cellular responses to drug toxicity
    Alison Hege Harrill
    University of North Carolina at Chapel Hill, 0031 Michael Hooker Research Center, Curriculum in Toxicology, CB 7431, Chapel Hill, NC, 27599, USA
    Expert Opin Drug Metab Toxicol 4:1379-89. 2008

Detail Information

Publications90

  1. pmc FastMap: fast eQTL mapping in homozygous populations
    Daniel M Gatti
    Department of Environmental Sciences and Engineering, University of North Carolina, Chapel Hill, North Carolina 27599, USA
    Bioinformatics 25:482-9. 2009
    ..However, existing eQTL mapping software does not scale well when the number of transcripts and markers are on the order of 10(5) and 10(5)-10(6), respectively...
  2. pmc Epigenetic alterations in liver of C57BL/6J mice after short-term inhalational exposure to 1,3-butadiene
    Igor Koturbash
    Division of Biochemical Toxicology, National Center for Toxicological Research, U S Food and Drug Administration, Jefferson, Arkansas, USA
    Environ Health Perspect 119:635-40. 2011
    ..1,3-Butadiene (BD) is a high-volume industrial chemical and a known human carcinogen. The main mode of BD carcinogenicity is thought to involve formation of genotoxic epoxides...
  3. pmc Mechanisms of HCV-induced liver cancer: what did we learn from in vitro and animal studies?
    Ivan Rusyn
    Department of Environmental Sciences and Engineering, University of North Carolina, Chapel Hill, NC 27599, USA Electronic address
    Cancer Lett 345:210-5. 2014
    ....
  4. pmc Trichloroethylene: Mechanistic, epidemiologic and other supporting evidence of carcinogenic hazard
    Ivan Rusyn
    University of North Carolina, Chapel Hill, NC, USA Electronic address
    Pharmacol Ther 141:55-68. 2014
    ..In all, consideration of the multiple evidence streams presented herein informed the IARC conclusions regarding the carcinogenicity of TCE. ..
  5. pmc Mechanistic considerations for human relevance of cancer hazard of di(2-ethylhexyl) phthalate
    Ivan Rusyn
    Department of Environmental Sciences and Engineering, University of North Carolina, Chapel Hill, NC 27599 7431, USA
    Mutat Res 750:141-58. 2012
    ..g., liver and testis) in rats and mice can not be ruled out and DEHP was classified as possibly carcinogenic to humans (Group 2B)...
  6. pmc Predictive modeling of chemical hazard by integrating numerical descriptors of chemical structures and short-term toxicity assay data
    Ivan Rusyn
    Department of Environmental Sciences and Engineering, University of North Carolina, Chapel Hill, North Carolina 27599, USA
    Toxicol Sci 127:1-9. 2012
    ....
  7. pmc Modes of action and species-specific effects of di-(2-ethylhexyl)phthalate in the liver
    Ivan Rusyn
    Department of Environmental Sciences and Engineering, School of Public Health, University of North Carolina, Chapel Hill, 27599 7431, USA
    Crit Rev Toxicol 36:459-79. 2006
    ....
  8. pmc Computational toxicology: realizing the promise of the toxicity testing in the 21st century
    Ivan Rusyn
    Department of Environmental Sciences and Engineering, School of Public Health, University of North Carolina Chapel Hill, Chapel Hill, North Carolina 27599 7431, USA
    Environ Health Perspect 118:1047-50. 2010
    ....
  9. ncbi request reprint Expression of base excision DNA repair genes is a sensitive biomarker for in vivo detection of chemical-induced chronic oxidative stress: identification of the molecular source of radicals responsible for DNA damage by peroxisome proliferators
    Ivan Rusyn
    Laboratory of Environmental Genomics, Department of Environmental Sciences and Engineering, University of North Carolina School of Public Health, Chapel Hill, North Carolina 27599, USA
    Cancer Res 64:1050-7. 2004
    ....
  10. pmc Systems biology and functional genomics approaches for the identification of cellular responses to drug toxicity
    Alison Hege Harrill
    University of North Carolina at Chapel Hill, 0031 Michael Hooker Research Center, Curriculum in Toxicology, CB 7431, Chapel Hill, NC, 27599, USA
    Expert Opin Drug Metab Toxicol 4:1379-89. 2008
    ....
  11. pmc Time-course comparison of xenobiotic activators of CAR and PPARalpha in mouse liver
    Pamela K Ross
    Department of Environmental Sciences and Engineering, University of North Carolina, Chapel Hill, NC 27599 7431, USA
    Toxicol Appl Pharmacol 235:199-207. 2009
    ....
  12. ncbi request reprint WY-14,643 induced cell proliferation and oxidative stress in mouse liver are independent of NADPH oxidase
    Courtney G Woods
    Department of Environmental Sciences and Engineering, University of North Carolina, Chapel Hill, North Carolina 27599 7431, USA
    Toxicol Sci 98:366-74. 2007
    ..These results provide new insight for understanding the mode of hepatocarcinogenic action of peroxisome proliferators...
  13. pmc Epigenetic mechanisms of mouse interstrain variability in genotoxicity of the environmental toxicant 1,3-butadiene
    Igor Koturbash
    Division of Biochemical Toxicology, National Center for Toxicological Research, U S Food and Drug Administration, Jefferson, Arkansas 72079, USA
    Toxicol Sci 122:448-56. 2011
    ..These findings demonstrate that interstrain susceptibility to genotoxicity by a well-known environmental carcinogen may be due to strain-specific epigenetic events in response to the exposure...
  14. pmc Hepatic epigenetic phenotype predetermines individual susceptibility to hepatic steatosis in mice fed a lipogenic methyl-deficient diet
    Igor P Pogribny
    Division of Biochemical Toxicology, National Center for Toxicological Research, Jefferson, AR 72079, USA
    J Hepatol 51:176-86. 2009
    ..However, the role of epigenetic alterations in the genesis of hepatic steatosis and cause of individual susceptibilities to this pathological state are largely unknown...
  15. pmc Time course investigation of PPARalpha- and Kupffer cell-dependent effects of WY-14,643 in mouse liver using microarray gene expression
    Courtney G Woods
    Department of Environmental Sciences and Engineering, University of North Carolina, Chapel Hill, NC 27599 7431, USA
    Toxicol Appl Pharmacol 225:267-77. 2007
    ..To the contrary, a strong PPARalpha-specific gene signature was evident in mice that were continually exposed to WY-14,643...
  16. pmc Sustained formation of alpha-(4-pyridyl-1-oxide)-N-tert-butylnitrone radical adducts in mouse liver by peroxisome proliferators is dependent upon peroxisome proliferator-activated receptor-alpha, but not NADPH oxidase
    Courtney G Woods
    Department of Environmental Sciences and Engineering, University of North Carolina, 0031 Michael Hooker Research Center, Chapel Hill, NC 27599 7431, USA
    Free Radic Biol Med 42:335-42. 2007
    ..Therefore, peroxisome proliferator-induced POBN radical production in Kupffer cells may be limited to an acute response to these compounds in mouse liver...
  17. ncbi request reprint Genetic and epigenetic changes in fibrosis-associated hepatocarcinogenesis in mice
    Grace Chappell
    Department of Environmental Sciences and Engineering, University of North Carolina, Chapel Hill, NC
    Int J Cancer 134:2778-88. 2014
    ..In summary, our results suggest that epigenetic events, rather than mutations in known cancer-related genes, play a prominent role in increased incidence of liver tumors in this mouse model of fibrosis-associated liver cancer...
  18. doi request reprint Strain-dependent dysregulation of one-carbon metabolism in male mice is associated with choline- and folate-deficient diet-induced liver injury
    Igor P Pogribny
    Division of Biochemical Toxicology, National Center for Toxicological Research, U S Food and Drug Administration, Jefferson, AR 72079, USA
    FASEB J 27:2233-43. 2013
    ....
  19. pmc Effects of polymorphisms in alcohol metabolism and oxidative stress genes on survival from head and neck cancer
    Anne M Hakenewerth
    Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA
    Cancer Epidemiol 37:479-91. 2013
    ..We hypothesized that polymorphisms in alcohol metabolism-related and antioxidant genes influence SCCHN survival...
  20. pmc Interstrain differences in the liver effects of trichloroethylene in a multistrain panel of inbred mice
    Blair U Bradford
    Department of Environmental Sciences and Engineering, University of North Carolina, Chapel Hill, North Carolina 27599, USA
    Toxicol Sci 120:206-17. 2011
    ..These studies provide better understanding of the mechanisms of TCE-induced toxicity anchored on metabolism and genotype-phenotype correlations that may define susceptibility or resistance...
  21. pmc Interstrain differences in the severity of liver injury induced by a choline- and folate-deficient diet in mice are associated with dysregulation of genes involved in lipid metabolism
    Volodymyr Tryndyak
    Division of Biochemical Toxicology, National Center for Toxicological Research, US Food and Drug Administration, Jefferson, Arkansas 72079, USA
    FASEB J 26:4592-602. 2012
    ..These findings suggest that the PPARĪ±-regulated metabolism network is one of the key mechanisms determining interstrain susceptibility and severity of NAFLD in mice...
  22. ncbi request reprint Plasma microRNAs are sensitive indicators of inter-strain differences in the severity of liver injury induced in mice by a choline- and folate-deficient diet
    Volodymyr P Tryndyak
    Division of Biochemical Toxicology, National Center for Toxicological Research, Jefferson, AR 72079, USA
    Toxicol Appl Pharmacol 262:52-9. 2012
    ..These observations suggest that the plasma levels of miRNAs may be used as biomarkers for noninvasive monitoring the extent of NAFLD-associated liver injury and susceptibility to NAFLD...
  23. pmc Gene expression in nontumoral liver tissue and recurrence-free survival in hepatitis C virus-positive hepatocellular carcinoma
    Masato Tsuchiya
    Department of Environmental Sciences and Engineering, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, NC, USA
    Mol Cancer 9:74. 2010
    ..Additional nontumoral liver samples were obtained from HCV-free subjects with metastatic liver tumors. Gene expression profiling data was used to determine the molecular signature of HCV-associated HCC and to develop a predictor of RFS...
  24. pmc Interstrain differences in liver injury and one-carbon metabolism in alcohol-fed mice
    Masato Tsuchiya
    Department of Environmental Sciences and Engineering, University of North Carolina, Chapel Hill, NC 27599, USA
    Hepatology 56:130-9. 2012
    ..The most pronounced effects that were closely associated with the degree of liver injury were hyperhomocysteinemia and strain-dependent differences in expression patterns of one-carbon metabolism-related genes...
  25. pmc Epigenetic effects of the continuous exposure to peroxisome proliferator WY-14,643 in mouse liver are dependent upon peroxisome proliferator activated receptor alpha
    Igor P Pogribny
    Division of Biochemical Toxicology, National Center for Toxicological Research, Jefferson, AR 72079, USA
    Mutat Res 625:62-71. 2007
    ..These data indicate the importance of epigenetic alterations in the mechanism of action of peroxisome proliferators and the key role of Pparalpha...
  26. pmc Mechanisms of peroxisome proliferator-induced DNA hypomethylation in rat liver
    Igor P Pogribny
    Division of Biochemical Toxicology, National Center for Toxicological Research, 3900 NCTR Road, Jefferson, AR 72079, USA
    Mutat Res 644:17-23. 2008
    ....
  27. pmc Population-based discovery of toxicogenomics biomarkers for hepatotoxicity using a laboratory strain diversity panel
    Alison H Harrill
    Department of Environmental Sciences and Engineering, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA
    Toxicol Sci 110:235-43. 2009
    ..Our data demonstrate that a multistrain approach may provide utility for understanding genotype-independent toxicity responses and facilitate identification of novel targets of therapeutic intervention...
  28. pmc Mechanism for prevention of alcohol-induced liver injury by dietary methyl donors
    Christine L Powell
    Department of Environmental Sciences and Engineering, University of North Carolina, Chapel Hill, North Carolina 27599, USA
    Toxicol Sci 115:131-9. 2010
    ..Profound changes in alcohol metabolism represent additional important mechanism of the protective effect of methyl donors in ALI...
  29. pmc Sex-specific gene expression in the BXD mouse liver
    Daniel M Gatti
    Department of Environmental Sciences and Engineering, University of North Carolina, Chapel Hill, North Carolina 27599, USA
    Physiol Genomics 42:456-68. 2010
    ..This study enhances our understanding of sex differences at the genome level and between species, as well as increasing our knowledge of the molecular underpinnings of sex differences in responses to xenobiotics...
  30. pmc Chronic administration of ethanol leads to an increased incidence of hepatocellular adenoma by promoting H-ras-mutated cells
    Emmanuelle Jeannot
    Department of Environmental Sciences and Engineering, University of North Carolina, Chapel Hill, 27599 7431, United States
    Cancer Lett 301:161-7. 2011
    ..We show that ethanol does not cause detectable oxidative stress in the liver at any time point and acts by promoting H-ras mutated cells...
  31. pmc Increased incidence of aflatoxin B1-induced liver tumors in hepatitis virus C transgenic mice
    Emmanuelle Jeannot
    Department of Environmental Sciences and Engineering, University of North Carolina, Chapel Hill, NC 27599 7431, USA
    Int J Cancer 130:1347-56. 2012
    ..In summary, HCV proteins core, E1, E2 and p7 are sufficient to reproduce the cocarcinogenic effect of HCV and AFB1, which is a known clinical phenomenon...
  32. pmc Protective effect of Juzen-taiho-to on hepatocarcinogenesis is mediated through the inhibition of Kupffer cell-induced oxidative stress
    Masato Tsuchiya
    Department of Environmental Sciences and Engineering, School of Public Health, University of North Carolina at Chapel Hill, USA
    Int J Cancer 123:2503-11. 2008
    ..This leads to lower levels of pro-inflammatory cytokines and oxidants in liver which may slow down the process of hepatocarcinogenesis and improves hepatic recurrence-free survival in patients with HCC...
  33. pmc Acetaminophen-induced acute liver injury in HCV transgenic mice
    Takeki Uehara
    Department of Environmental Sciences and Engineering, University of North Carolina, Chapel Hill, NC 27599, USA
    Toxicol Appl Pharmacol 266:224-32. 2013
    ..In fed mice dosed with 300 mg/kg acetaminophen, we observed that liver mitochondria in HCV-Tg mice exhibited signs of dysfunction showing the potential mechanism for increased susceptibility...
  34. ncbi request reprint Predictive power of biomarkers of oxidative stress and inflammation in patients with hepatitis C virus-associated hepatocellular carcinoma
    Akira Maki
    Department of Environmental Sciences and Engineering, School of Public Health, University of North Carolina at Chapel Hill, CB 7431, Chapel Hill, North Carolina 27599, USA
    Ann Surg Oncol 14:1182-90. 2007
    ..This study evaluated the relationship between inflammation, intra-hepatic oxidative stress, oxidative DNA damage and the progression of liver carcinogenesis in hepatitis C virus (HCV)-infected humans...
  35. pmc Liquid chromatography electrospray ionization tandem mass spectrometry analysis method for simultaneous detection of trichloroacetic acid, dichloroacetic acid, S-(1,2-dichlorovinyl)glutathione and S-(1,2-dichlorovinyl)-L-cysteine
    Sungkyoon Kim
    Department of Environmental Sciences and Engineering, School of Public Health, University of North Carolina, CB 7431, Chapel Hill, NC 27599, USA
    Toxicology 262:230-8. 2009
    ..037+/-0.015 nmol/ml (0.001 nmol/ml); DCVC, 0.0024+/-0.0009 nmol/ml (0.001 nmol/ml). This method opens new opportunities to increase throughput and decrease number of animals required for mechanistic studies on TCE in rodents...
  36. pmc Evaluation of an in vitro toxicogenetic mouse model for hepatotoxicity
    Stephanie M Martinez
    Department of Environmental Sciences and Engineering, University of North Carolina at Chapel Hill, NC 27599, USA
    Toxicol Appl Pharmacol 249:208-16. 2010
    ..Strain-specific responses to toxicant exposure have been observed in cultured hepatocytes and these experiments open new opportunities for further developments of in vitro models of hepatotoxicity in a genetically diverse population...
  37. pmc Role of epigenetic aberrations in the development and progression of human hepatocellular carcinoma
    Igor P Pogribny
    Division of Biochemical Toxicology, National Center for Toxicological Research, Jefferson, AR 72079, United States Electronic address
    Cancer Lett 342:223-30. 2014
    ....
  38. doi request reprint Difference in expression of hepatic microRNAs miR-29c, miR-34a, miR-155, and miR-200b is associated with strain-specific susceptibility to dietary nonalcoholic steatohepatitis in mice
    Igor P Pogribny
    Division of Biochemical Toxicology, National Center for Toxicological Research, Jefferson, AR 72079, USA
    Lab Invest 90:1437-46. 2010
    ..More important, our data provide a mechanistic link between alterations in miRNA expression and pathophysiological and pathomorphological features of NASH...
  39. ncbi request reprint Temporal correlation of pathology and DNA damage with gene expression in a choline-deficient model of rat liver injury
    Christine L Powell
    Curriculum in Toxicology, School of Medicine, University of North Carolina, Chapel Hill, NC 27599 7431, USA
    Hepatology 42:1137-47. 2005
    ....
  40. pmc Replication and narrowing of gene expression quantitative trait loci using inbred mice
    Daniel M Gatti
    Department of Environmental Sciences and Engineering, University of North Carolina, CB 7431, Chapel Hill, NC 27599, USA
    Mamm Genome 20:437-46. 2009
    ....
  41. pmc Metabolomic profiling of a modified alcohol liquid diet model for liver injury in the mouse uncovers new markers of disease
    Blair U Bradford
    Department of Environmental Sciences and Engineering, 0031 Michael Hooker Research Center, CB 7431, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599 7431, USA
    Toxicol Appl Pharmacol 232:236-43. 2008
    ..Changes in the latter two metabolites suggest an inhibition of the kidney enzyme aminoacylase I and may be useful as markers for alcohol consumption...
  42. pmc Comparative analysis of promoter methylation and gene expression endpoints between tumorous and non-tumorous tissues from HCV-positive patients with hepatocellular carcinoma
    Eric J Formeister
    Department of Environmental Sciences and Engineering, University of North Carolina, Chapel Hill, NC, USA
    Mutat Res 692:26-33. 2010
    ..The finding that RIZ1 methylation and increased levels of LINE-1 hypomethylation in non-tumorous tissues are associated with time to recurrence underscores the importance of assessing the epigenetic state of the liver remnant...
  43. pmc MicroRNA expression in the livers of inbred mice
    Daniel M Gatti
    Department of Environmental Sciences and Engineering, University of North Carolina, Chapel Hill, NC 27599, USA
    Mutat Res 714:126-33. 2011
    ....
  44. pmc Increased oxidative stress is associated with balanced increases in hepatocyte apoptosis and proliferation in glycerol-3-phosphate acyltransferase-1 deficient mice
    Linda E Hammond
    Department of Nutrition, CB 7461, 2301 Michael Hooker Research Building, Columbia Street, University of North Carolina, Chapel Hill, NC 27599, USA
    Exp Mol Pathol 82:210-9. 2007
    ..Thus, Gpat1-/- liver exhibits increased oxidative stress and sensitivity of the mitochondrial permeability transition pore, and a balanced increase in apoptosis and proliferation...
  45. ncbi request reprint Effects of ethylene oxide and ethylene inhalation on DNA adducts, apurinic/apyrimidinic sites and expression of base excision DNA repair genes in rat brain, spleen, and liver
    Ivan Rusyn
    Department of Environmental Sciences and Engineering, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA
    DNA Repair (Amst) 4:1099-110. 2005
    ..We conclude that accumulation of AP sites is not a likely primary mechanism for mutagenicity and carcinogenicity of EO...
  46. pmc Mouse population-guided resequencing reveals that variants in CD44 contribute to acetaminophen-induced liver injury in humans
    Alison H Harrill
    Curriculum in Toxicology, University of North Carolina, Chapel Hill, North Carolina 27599, USA
    Genome Res 19:1507-15. 2009
    ..These studies demonstrate that a diverse mouse population can be used to understand and predict adverse toxicity in heterogeneous human populations through guided resequencing...
  47. pmc Phenotypic anchoring of acetaminophen-induced oxidative stress with gene expression profiles in rat liver
    Christine L Powell
    Curriculum in Toxicology and Department of Environmental Sciences and Engineering, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA
    Toxicol Sci 93:213-22. 2006
    ....
  48. pmc SAFEGUI: resampling-based tests of categorical significance in gene expression data made easy
    Daniel M Gatti
    Department of Environmental Sciences and Engineering, Department of Biostatistics, University of North Carolina, Chapel Hill, NC 27599, USA
    Bioinformatics 25:541-2. 2009
    ..SAFEGUI incorporates both permutation and more recently proposed bootstrap algorithms that are demonstrated to be more powerful in detecting differential expression across categories of genes...
  49. pmc Genome-level analysis of genetic regulation of liver gene expression networks
    Daniel Gatti
    Department of Environmental Sciences and Engineering, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA
    Hepatology 46:548-57. 2007
    ..genenetwork.org) that allows custom data mining, identification of coregulated transcripts and correlated phenotypes, cross-tissue, and cross-species comparisons, as well as testing of a broad array of hypotheses...
  50. pmc Epigenetic aspects of genotoxic and non-genotoxic hepatocarcinogenesis: studies in rodents
    Igor P Pogribny
    Division of Biochemical Toxicology, National Center for Toxicological Research, Jefferson, Arkansas 72079, USA
    Environ Mol Mutagen 49:9-15. 2008
    ....
  51. pmc A systematic approach for identifying and presenting mechanistic evidence in human health assessments
    Mary E Kushman
    Department of Environmental Sciences and Engineering, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC, United States
    Regul Toxicol Pharmacol 67:266-77. 2013
    ..This approach contributes to human health assessment by effectively managing a large volume of literature, improving transparency, and facilitating subsequent synthesis of information across studies. ..
  52. pmc Integrative chemical-biological read-across approach for chemical hazard classification
    Yen Low
    Laboratory for Molecular Modeling, Division of Chemical Biology and Medicinal Chemistry, University of North Carolina, Chapel Hill, North Carolina 27599, USA
    Chem Res Toxicol 26:1199-208. 2013
    ..Identification of both chemical and biological features that give rise to the high accuracy of CBRA-based toxicity prediction facilitates mechanistic interpretation of the models. ..
  53. pmc Molecular mechanisms of fibrosis-associated promotion of liver carcinogenesis
    Takeki Uehara
    Department of Environmental Sciences and Engineering, University of North Carolina, Chapel Hill, NC, USA
    Toxicol Sci 132:53-63. 2013
    ..These results may contribute to identification of cirrhotic patients predisposed to HCC by analyzing the expression of hepatic progenitor cell markers in the noncancerous liver tissue...
  54. pmc ToxPi GUI: an interactive visualization tool for transparent integration of data from diverse sources of evidence
    David M Reif
    National Center for Computational Toxicology, U S Environmental Protection Agency, Durham, NC, USA
    Bioinformatics 29:402-3. 2013
    ..Thus, the ToxPi bridges a gap, combining rigorous aggregation of evidence with ease of communication to stakeholders...
  55. ncbi request reprint Cytochrome P450 CYP2E1, but not nicotinamide adenine dinucleotide phosphate oxidase, is required for ethanol-induced oxidative DNA damage in rodent liver
    Blair U Bradford
    Department of Environmental Sciences and Engineering, School of Public Health, University of North Carolina, Chapel Hill, NC 27599 7431, USA
    Hepatology 41:336-44. 2005
    ....
  56. pmc Computational tools for discovery and interpretation of expression quantitative trait loci
    Fred A Wright
    Department of Biostatistics, University of North Carolina, Chapel Hill, NC 27599, USA
    Pharmacogenomics 13:343-52. 2012
    ..The purpose of this review is to help investigators find appropriate programs for eQTL analysis and interpretation...
  57. pmc Heading down the wrong pathway: on the influence of correlation within gene sets
    Daniel M Gatti
    Department of Environmental Sciences and Engineering, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
    BMC Genomics 11:574. 2010
    ..Most popular gene set testing methods assume the independence of genes within each set, an assumption that is seriously violated, as extensive correlation between genes is a well-documented phenomenon...
  58. pmc Toxicogenetics: population-based testing of drug and chemical safety in mouse models
    Ivan Rusyn
    Department of Environmental Sciences and Engineering, 0031 Michael Hooker Research Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
    Pharmacogenomics 11:1127-36. 2010
    ....
  59. pmc In vitro screening for population variability in chemical toxicity
    Shannon H O'Shea
    Department of Environmental Sciences and Engineering, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, NC 27599, USA
    Toxicol Sci 119:398-407. 2011
    ....
  60. pmc Identification of putative estrogen receptor-mediated endocrine disrupting chemicals using QSAR- and structure-based virtual screening approaches
    Liying Zhang
    Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, NC, USA
    Toxicol Appl Pharmacol 272:67-76. 2013
    ....
  61. pmc Quantitative high-throughput screening for chemical toxicity in a population-based in vitro model
    Eric F Lock
    University of North Carolina, Chapel Hill, North Carolina 27599, USA
    Toxicol Sci 126:578-88. 2012
    ....
  62. pmc Use of cell viability assay data improves the prediction accuracy of conventional quantitative structure-activity relationship models of animal carcinogenicity
    Hao Zhu
    Carolina Environmental Bioinformatics Research Center, University of North Carolina, Chapel Hill, NC 27599 7360, USA
    Environ Health Perspect 116:506-13. 2008
    ..The first HTS results for a set of 1,408 compounds tested for their effects on cell viability in six different cell lines have recently become available via PubChem...
  63. pmc A novel two-step hierarchical quantitative structure-activity relationship modeling work flow for predicting acute toxicity of chemicals in rodents
    Hao Zhu
    Laboratory for Molecular Modeling, Division of Medicinal Chemistry and Natural Products, School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599 7360, USA
    Environ Health Perspect 117:1257-64. 2009
    ..Accurate prediction of in vivo toxicity from in vitro testing is a challenging problem. Large public-private consortia have been formed with the goal of improving chemical safety assessment by the means of high-throughput screening...
  64. ncbi request reprint Expression of base excision DNA repair genes as a biomarker of oxidative DNA damage
    Christine L Powell
    Curriculum in Toxicology and Department of Environmental Sciences and Engineering, School of Public Health, University of North Carolina, Chapel Hill, NC 27599, USA
    Cancer Lett 229:1-11. 2005
    ..Here, we demonstrate the utility of measuring changes in expression of BER genes as a sensitive in vivo biomarker for oxidative DNA damage...
  65. pmc Modeling liver-related adverse effects of drugs using knearest neighbor quantitative structure-activity relationship method
    Amie D Rodgers
    Curriculum in Toxicology, Division of Medicinal Chemistry and Natural Products, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA
    Chem Res Toxicol 23:724-32. 2010
    ....
  66. ncbi request reprint Predicting drug-induced hepatotoxicity using QSAR and toxicogenomics approaches
    Yen Low
    Laboratory for Molecular Modeling, University of North Carolina, Chapel Hill, North Carolina 27599, United States
    Chem Res Toxicol 24:1251-62. 2011
    ....
  67. ncbi request reprint Swift increase in alcohol metabolism (SIAM): understanding the phenomenon of hypermetabolism in liver
    Blair U Bradford
    Department of Environmental Sciences and Engineering, School of Public Health, University of North Carolina, Chapel Hill, 27599 7431, USA
    Alcohol 35:13-7. 2005
    ....
  68. ncbi request reprint Protective effect of glycine on renal injury induced by ischemia-reperfusion in vivo
    Ming Yin
    Department of Pharmacology, School of Medicine, University of North Carolina, Chapel Hill 27599, USA
    Am J Physiol Renal Physiol 282:F417-23. 2002
    ..In conclusion, these results indicate that administration of glycine indeed reduces mild ischemia-reperfusion injury in the kidney in vivo, in part by decreasing initial damage and preventing chronic hypoxia...
  69. ncbi request reprint Simulating association studies: a data-based resampling method for candidate regions or whole genome scans
    Fred A Wright
    Department of Biostatistics, University of North Carolina, Chapel Hill, NC 27599, USA
    Bioinformatics 23:2581-8. 2007
    ..Improvements in study design and analytic techniques will require the simulation of datasets with realistic patterns of linkage disequilibrium and allele frequencies for typed SNPs...
  70. pmc Discovering collectively informative descriptors from high-throughput experiments
    Clark D Jeffries
    Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, NC, USA
    BMC Bioinformatics 10:431. 2009
    ..Combining information from these studies can increase the reliability and generalizability of results and also yield new insights that guide future research...
  71. pmc Integrated study of copy number states and genotype calls using high-density SNP arrays
    Wei Sun
    Department of Biostatistics, University of North Carolina, Chapel Hill, NC, USA
    Nucleic Acids Res 37:5365-77. 2009
    ..We evaluated genoCN by applications to 162 HapMap individuals and a brain tumor (glioblastoma) dataset and showed that our method can successfully identify both types of copy number differences and produce high-quality genotype calls...
  72. ncbi request reprint Information perspectives of the Haseman-Elston method
    Fred A Wright
    Department of Biostatistics and Lineberger Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599 7420, USA
    Hum Hered 55:132-42. 2003
    ..The results provide insight and analytic results that apply to general phenotype distributions and can be used to judge the effects of various data transformations and selective sampling of extreme phenotypes...
  73. pmc Pharmacokinetic analysis of trichloroethylene metabolism in male B6C3F1 mice: Formation and disposition of trichloroacetic acid, dichloroacetic acid, S-(1,2-dichlorovinyl)glutathione and S-(1,2-dichlorovinyl)-L-cysteine
    Sungkyoon Kim
    Department of Environmental Sciences and Engineering, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, NC 27599, USA
    Toxicol Appl Pharmacol 238:90-9. 2009
    ..These pharmacokinetic studies provide insight into the kinetic properties of four key biomarkers of TCE toxicity in the mouse, representing novel information that can be used in risk assessment...
  74. pmc Joint effects of alcohol consumption and polymorphisms in alcohol and oxidative stress metabolism genes on risk of head and neck cancer
    Anne M Hakenewerth
    Department of Epidemiology, University of North Carolina at Chapel Hill, 100 Market Street, Chapel Hill, NC 27516, USA
    Cancer Epidemiol Biomarkers Prev 20:2438-49. 2011
    ..Genetic variation in the oxidative stress pathway may impact the carcinogenic effect of reactive oxygen species produced by ethanol metabolism. We hypothesized that alcohol interacts with these pathways to affect SCCHN incidence...
  75. ncbi request reprint Genomic profiling in nuclear receptor-mediated toxicity
    Courtney G Woods
    Department of Environmental Sciences and Engineering, University of North Carolina, Chapel Hill, North Carolina 27599 7431, USA
    Toxicol Pathol 35:474-94. 2007
    ..This review will focus on genomics studies related to PPAR, CAR, PXR, RXR, LXR, FXR, and AHR...
  76. ncbi request reprint Significance analysis of functional categories in gene expression studies: a structured permutation approach
    William T Barry
    Department of Biostatistics, University of North Carolina at Chapel Hill, 27599 7420, USA
    Bioinformatics 21:1943-9. 2005
    ..SAFE is a two-stage, permutation-based method that can be applied to various experimental designs, accounts for the unknown correlation among genes and enables permutation-based estimation of error rates...
  77. ncbi request reprint Impaired Ras membrane association and activation in PPARalpha knockout mice after partial hepatectomy
    Michael D Wheeler
    Laboratory of Hepatobiology and Toxicology, Department of Pharmacology, Curriculum in Toxicology, School of Medicine, University of North Carolina, Chapel Hill, North Carolina 27599, USA
    Am J Physiol Gastrointest Liver Physiol 284:G302-12. 2003
    ..Collectively, these results support the hypothesis that PPARalpha is necessary for cell cycle progression in regenerating mouse liver via mechanisms involving prenylation of small GTPases Ras and RhoA...
  78. pmc Adiponectin lowers glucose production by increasing SOGA
    Rachael B Cowherd
    Departments of Nutrition, School of Medicine and Gillings School of Global Public Health, University of North Carolina, Chapel Hill, North Carolina 27599, USA
    Am J Pathol 177:1936-45. 2010
    ..Circulating SOGA increased in parallel with adiponectin and insulin activity in both humans and mice. These results suggest that adiponectin-mediated increases in SOGA contribute to the inhibition of glucose production...
  79. doi request reprint Age-dependent variability in gene expression in male Fischer 344 rat retina
    Zhen Li
    Department of Biostatistics, Carolina Environmental Bioinformatics Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA
    Toxicol Sci 107:281-92. 2009
    ..Our data suggest that population stochastically induced variability should be considered in assessing sensitivity due to old age...
  80. pmc Large-scale gene expression differences across brain regions and inbred strains correlate with a behavioral phenotype
    Jessica J Nadler
    Department of Genetics, Carolina Center for Genome Sciences, University of North Carolina, Chapel Hill 27599 7264, USA
    Genetics 174:1229-36. 2006
    ..Thus we can begin to identify expression profiles contributing to behavioral phenotypes through variation in gene expression...
  81. pmc Gene expression in peripheral blood leukocytes in monozygotic twins discordant for chronic fatigue: no evidence of a biomarker
    Andrea Byrnes
    Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America
    PLoS ONE 4:e5805. 2009
    ..Chronic fatiguing illness remains a poorly understood syndrome of unknown pathogenesis. We attempted to identify biomarkers for chronic fatiguing illness using microarrays to query the transcriptome in peripheral blood leukocytes...
  82. pmc Transcriptional response of rat frontal cortex following acute in vivo exposure to the pyrethroid insecticides permethrin and deltamethrin
    Joshua A Harrill
    Curriculum in Toxicology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA
    BMC Genomics 9:546. 2008
    ..The purpose of this study was to characterize and explore changes in gene expression that occur in the rat frontal cortex, an area of CNS affected by pyrethroids, following an acute low-dose exposure...
  83. ncbi request reprint Mouse liver effects of cyproconazole, a triazole fungicide: role of the constitutive androstane receptor
    Richard C Peffer
    Syngenta Crop Protection, Inc, Greensboro, North Carolina 27419, USA
    Toxicol Sci 99:315-25. 2007
    ..These experiments demonstrate that short-term liver effects of cyproconazole in mice are CAR-dependent and similar to those of phenobarbital, a known nongenotoxic rodent liver carcinogen...
  84. ncbi request reprint Role of the Kupffer cell in mediating hepatic toxicity and carcinogenesis
    Ruth A Roberts
    AstraZeneca, Safety Assessment Alderley Park, Macclesfield, Cheshire, SK10 4TG United Kingdom
    Toxicol Sci 96:2-15. 2007
    ..Taken together, the data presented in this symposium illustrate to the toxicologist the central role played by Kupffer cells in mediating hepatotoxicity...
  85. ncbi request reprint Electron spin resonance and spin trapping technique provide direct evidence that edaravone prevents acute ischemia-reperfusion injury of the liver by limiting free radical-mediated tissue damage
    Hiroshi Kono
    First Department of Surgery, University of Yamanashi, Yamanashi, Japan
    Free Radic Res 40:579-88. 2006
    ..These results demonstrate that edaravone is an effective blocker of free radicals in vivo in the liver after ischemia/reperfusion, leading to prevention of organ injury by limiting the deleterious effects of free radicals...
  86. ncbi request reprint Role of peroxisome proliferator-activated receptor-alpha (PPARalpha) in bezafibrate-induced hepatocarcinogenesis and cholestasis
    Thomas Hays
    Department of Veterinary Science and Center for Molecular Toxicology and Carcinogenesis, The Pennsylvania State University, University Park, PA 16802, USA
    Carcinogenesis 26:219-27. 2005
    ..Results from these studies demonstrate that the PPARalpha is required to mediate hepatocarcinogenesis induced by bezafibrate, and that PPARalpha protects against potential cholestasis...
  87. ncbi request reprint Multicenter study of acetaminophen hepatotoxicity reveals the importance of biological endpoints in genomic analyses
    Richard P Beyer
    University of Washington, and Fred Hutchinson Cancer Research Center, Seattle, Washington 98195, USA
    Toxicol Sci 99:326-37. 2007
    ..We show that phenotypic anchoring of gene expression data is required for biologically meaningful analysis of toxicogenomic experiments...
  88. pmc Transcriptional networks in S. cerevisiae linked to an accumulation of base excision repair intermediates
    Ivan Rusyn
    Center for Environmental Health Sciences and Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts, United States of America
    PLoS ONE 2:e1252. 2007
    ..Taken together, these results suggest that a branch point exists in the current model for DNA damage-signaled transcription in S. cerevisiae...
  89. ncbi request reprint Glycine as a potent anti-angiogenic nutrient for tumor growth
    Shunhei Yamashina
    Department of Gastroenterology, Juntendo University School of Medicine, Tokyo, Japan
    J Gastroenterol Hepatol 22:S62-4. 2007
    ..Therefore, glycine can be used not only for treatment of inflammation, but also for chemoprevention and treatment of carcinoma...
  90. ncbi request reprint Functional heterogeneity of the kupffer cell population is involved in the mechanism of gadolinium chloride in rats administered endotoxin
    Hiroshi Kono
    First Department of Surgery, Yamanashi Medical University, Yamanashi, 409 3898, Japan
    J Surg Res 106:179-87. 2002
    ..The purpose of this study was to determine if evidence of functional heterogeneity between subtypes of the Kupffer cell (KC) may be involved in the mechanism of the protective effect of gadolinium chloride (GdCl3) in endotoxemia...

Research Grants16

  1. DNA REPAIR AND SUSCEPTIBILITY TO ENVIRONMENTAL AGENTS
    Ivan Rusyn; Fiscal Year: 2004
    ..These experiments will also provide crucial mechanistic insights into possible differences in species- and tissue-specific responses to DNA damage induced by environmental agents. ..
  2. Bioengineering partnership to improve chemical hazard testing paradigms
    Ivan Rusyn; Fiscal Year: 2009
    ..The partnership will be directed by Ivan Rusyn, M.D., Ph.D...
  3. Bioengineering partnership to improve chemical hazard testing paradigms
    Ivan Rusyn; Fiscal Year: 2010
    ..The partnership will be directed by Ivan Rusyn, M.D., Ph.D...
  4. FACILITATING GTEx, DISEASE, AND GxE ANALYSES VIA FAST EXPRESSION (e)QTL MAPPING
    Fred A Wright; Fiscal Year: 2010
    ..The project will create effective tools for elucidating the complex biology underlying disease. ..
  5. Metabolomic and Toxicogenetic Study of Ethanol Toxicity
    Ivan Rusyn; Fiscal Year: 2007
    ..abstract_text> ..
  6. Molecular Mechanisms of Phthalate-induced Carcinogenesis
    Ivan Rusyn; Fiscal Year: 2007
    ..This results in a "potentiation" of a non-specific mitogen release from Kupffer cells activated by lipid-like peroxisome proliferator particles, thus accounting for a characteristic burst of proliferation in the liver. ..
  7. Metabolomic and Toxicogenetic Study of Ethanol Toxicity
    Ivan Rusyn; Fiscal Year: 2006
    ..abstract_text> ..
  8. Molecular Mechanisms of Phthalate-induced Carcinogenesis
    Ivan Rusyn; Fiscal Year: 2006
    ..This results in a "potentiation" of a non-specific mitogen release from Kupffer cells activated by lipid-like peroxisome proliferator particles, thus accounting for a characteristic burst of proliferation in the liver. ..
  9. Metabolomic and Toxicogenetic Study of Ethanol Toxicity
    Ivan Rusyn; Fiscal Year: 2005
    ..abstract_text> ..
  10. Bioengineering partnership to improve chemical hazard testing paradigms
    Ivan Rusyn; Fiscal Year: 2010
    ....
  11. Molecular Mechanisms of Phthalate-induced Carcinogenesis
    Ivan Rusyn; Fiscal Year: 2004
    ..This results in a "potentiation" of a non-specific mitogen release from Kupffer cells activated by lipid-like peroxisome proliferator particles, thus accounting for a characteristic burst of proliferation in the liver. ..
  12. Metabolomic and Toxicogenetic Study of Ethanol Toxicity
    Ivan Rusyn; Fiscal Year: 2009
    ..abstract_text> ..
  13. Molecular Mechanisms of Phthalate-induced Carcinogenesis
    Ivan Rusyn; Fiscal Year: 2005
    ..This results in a "potentiation" of a non-specific mitogen release from Kupffer cells activated by lipid-like peroxisome proliferator particles, thus accounting for a characteristic burst of proliferation in the liver. ..
  14. Bioengineering partnership to improve chemical hazard testing paradigms
    Ivan Rusyn; Fiscal Year: 2011
    ....