Thomas Kensler

Summary

Affiliation: Johns Hopkins Bloomberg School of Public Health
Country: USA

Publications

  1. pmc Nrf2: friend or foe for chemoprevention?
    Thomas W Kensler
    Department of Environmental Health Sciences, Bloomberg School of Public Health, Johns Hopkins University, 615 North Wolfe Street, Baltimore, MD 21205, USA
    Carcinogenesis 31:90-9. 2010
  2. pmc Keap1-nrf2 signaling: a target for cancer prevention by sulforaphane
    Thomas W Kensler
    Department of Environmental Health Sciences, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205, USA
    Top Curr Chem 329:163-77. 2013
  3. pmc Modulation of the metabolism of airborne pollutants by glucoraphanin-rich and sulforaphane-rich broccoli sprout beverages in Qidong, China
    Thomas W Kensler
    Department of Environmental Health Sciences, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD 21205, USA
    Carcinogenesis 33:101-7. 2012
  4. ncbi request reprint Translational strategies for cancer prevention in liver
    Thomas W Kensler
    Department of Environmental Health Sciences, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland 21205, USA
    Nat Rev Cancer 3:321-9. 2003
  5. ncbi request reprint Strategies for chemoprevention of liver cancer
    Thomas W Kensler
    Department of Environmental Health Sciences, Johns Hopkins Bloomberg School of Public Health, 615 North Wolfe Street, Baltimore, MD 21205, USA
    Eur J Cancer Prev 11:S58-64. 2002
  6. doi request reprint Is it time to advance the chemoprevention of environmental carcinogenesis with microdosing trials?
    Thomas W Kensler
    Department of Environmental Health Sciences, Johns Hopkins Bloomberg School of Public Health, 615 North Wolfe Street, Baltimore, MD 21205, USA
    Cancer Prev Res (Phila) 2:1003-7. 2009
  7. ncbi request reprint Cell survival responses to environmental stresses via the Keap1-Nrf2-ARE pathway
    Thomas W Kensler
    Department of Environmental Health Sciences, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205, USA
    Annu Rev Pharmacol Toxicol 47:89-116. 2007
  8. ncbi request reprint Chemoprevention of hepatocellular carcinoma in aflatoxin endemic areas
    Thomas W Kensler
    Department of Environmental Health Sciences, Johns Hopkins Bloomberg School of Public Health, 615 N Wolfe Street, Baltimore, Maryland 21205, USA
    Gastroenterology 127:S310-8. 2004
  9. ncbi request reprint Oltipraz chemoprevention trial in Qidong, People's Republic of China: modulation of serum aflatoxin albumin adduct biomarkers
    T W Kensler
    Department of Environmental Health Sciences, Johns Hopkins School of Hygiene and Public Health, Baltimore, Maryland 21205, USA
    Cancer Epidemiol Biomarkers Prev 7:127-34. 1998
  10. ncbi request reprint Use of aflatoxin adducts as intermediate endpoints to assess the efficacy of chemopreventive interventions in animals and man
    T W Kensler
    Department of Environmental Health Sciences, Johns Hopkins School of Hygiene and Public Health, Baltimore, MD 21205, USA
    Mutat Res 402:165-72. 1998

Detail Information

Publications83

  1. pmc Nrf2: friend or foe for chemoprevention?
    Thomas W Kensler
    Department of Environmental Health Sciences, Bloomberg School of Public Health, Johns Hopkins University, 615 North Wolfe Street, Baltimore, MD 21205, USA
    Carcinogenesis 31:90-9. 2010
    ..This review provides a synopsis of KEAP1-NRF2 signaling, compares the impact of genetic versus pharmacologic activation and considers both the attributes and concerns of targeting the pathway in chemoprevention...
  2. pmc Keap1-nrf2 signaling: a target for cancer prevention by sulforaphane
    Thomas W Kensler
    Department of Environmental Health Sciences, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205, USA
    Top Curr Chem 329:163-77. 2013
    ....
  3. pmc Modulation of the metabolism of airborne pollutants by glucoraphanin-rich and sulforaphane-rich broccoli sprout beverages in Qidong, China
    Thomas W Kensler
    Department of Environmental Health Sciences, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD 21205, USA
    Carcinogenesis 33:101-7. 2012
    ..No significant differences were seen between the effects of SFR versus GRR. Intervention with broccoli sprouts may enhance detoxication of airborne pollutants and attenuate their associated health risks...
  4. ncbi request reprint Translational strategies for cancer prevention in liver
    Thomas W Kensler
    Department of Environmental Health Sciences, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland 21205, USA
    Nat Rev Cancer 3:321-9. 2003
    ..In the developing world--where the burden of liver cancer is highest--immediate, practical and economical approaches are essential. So, targeted chemoprevention might be most appropriate for the present generation of individuals at risk...
  5. ncbi request reprint Strategies for chemoprevention of liver cancer
    Thomas W Kensler
    Department of Environmental Health Sciences, Johns Hopkins Bloomberg School of Public Health, 615 North Wolfe Street, Baltimore, MD 21205, USA
    Eur J Cancer Prev 11:S58-64. 2002
    ..Both chemopreventive agents modulated levels of aflatoxin biomarkers in the study participants in manners consonant with protection...
  6. doi request reprint Is it time to advance the chemoprevention of environmental carcinogenesis with microdosing trials?
    Thomas W Kensler
    Department of Environmental Health Sciences, Johns Hopkins Bloomberg School of Public Health, 615 North Wolfe Street, Baltimore, MD 21205, USA
    Cancer Prev Res (Phila) 2:1003-7. 2009
    ..We also reflect on what microdosing studies have taught us to date...
  7. ncbi request reprint Cell survival responses to environmental stresses via the Keap1-Nrf2-ARE pathway
    Thomas W Kensler
    Department of Environmental Health Sciences, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205, USA
    Annu Rev Pharmacol Toxicol 47:89-116. 2007
    ..This review highlights the key elements in this adaptive response to protection against acute and chronic cell injury provoked by environmental stresses...
  8. ncbi request reprint Chemoprevention of hepatocellular carcinoma in aflatoxin endemic areas
    Thomas W Kensler
    Department of Environmental Health Sciences, Johns Hopkins Bloomberg School of Public Health, 615 N Wolfe Street, Baltimore, Maryland 21205, USA
    Gastroenterology 127:S310-8. 2004
    ....
  9. ncbi request reprint Oltipraz chemoprevention trial in Qidong, People's Republic of China: modulation of serum aflatoxin albumin adduct biomarkers
    T W Kensler
    Department of Environmental Health Sciences, Johns Hopkins School of Hygiene and Public Health, Baltimore, Maryland 21205, USA
    Cancer Epidemiol Biomarkers Prev 7:127-34. 1998
    ..A follow-up Phase IIb trial with a longer intervention period will be necessary to determine the full extent to which aflatoxin biomarker burden can be reduced and whether diminution of biomarkers can be sustained over the long term...
  10. ncbi request reprint Use of aflatoxin adducts as intermediate endpoints to assess the efficacy of chemopreventive interventions in animals and man
    T W Kensler
    Department of Environmental Health Sciences, Johns Hopkins School of Hygiene and Public Health, Baltimore, MD 21205, USA
    Mutat Res 402:165-72. 1998
    ..The general approach that has been utilized for the development, validation and application of aflatoxin-DNA and protein adduct biomarkers to cancer chemoprevention trials is summarized...
  11. ncbi request reprint Conceptually new deltanoids (vitamin D analogs) inhibit multistage skin tumorigenesis
    T W Kensler
    Department of Environmental Health Sciences and Department of Epidemiology, School of Hygiene and Public Health, The Johns Hopkins University, Baltimore, MD 21205, USA
    Carcinogenesis 21:1341-5. 2000
    ....
  12. ncbi request reprint Chemoprotection by organosulfur inducers of phase 2 enzymes: dithiolethiones and dithiins
    T W Kensler
    Department of Environmental Health Sciences, Johns Hopkins School of Hygiene and Public Health, Baltimore, MD 21205, USA
    Drug Metabol Drug Interact 17:3-22. 2000
    ..Thus, identification and utilization of naturally-occurring organosulfur chemoprotectors including dithiins should be a high priority...
  13. ncbi request reprint Effects of glucosinolate-rich broccoli sprouts on urinary levels of aflatoxin-DNA adducts and phenanthrene tetraols in a randomized clinical trial in He Zuo township, Qidong, People's Republic of China
    Thomas W Kensler
    Department of Environmental Health Sciences, Bloomberg School of Public Health, Johns Hopkins University, Room E7541, 615 North Wolfe Street, Baltimore, MD 21205, USA
    Cancer Epidemiol Biomarkers Prev 14:2605-13. 2005
    ..29). Understanding factors influencing glucosinolate hydrolysis and bioavailability will be required for optimal use of broccoli sprouts in human interventions...
  14. pmc Genetic ablation of Nrf2 enhances susceptibility to cigarette smoke-induced emphysema in mice
    Tirumalai Rangasamy
    Department of Environmental Health Sciences, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland 21205, USA
    J Clin Invest 114:1248-59. 2004
    ..The responsiveness of the Nrf2 pathway may act as a major determinant of susceptibility to tobacco smoke-induced emphysema by upregulating antioxidant defenses and decreasing lung inflammation and alveolar cell apoptosis...
  15. ncbi request reprint Modulation of gene expression by cancer chemopreventive dithiolethiones through the Keap1-Nrf2 pathway. Identification of novel gene clusters for cell survival
    Mi Kyoung Kwak
    Department of Environmental Health Sciences, Johns Hopkins University Bloomberg School of Public Health, Baltimore, Maryland 21205, USA
    J Biol Chem 278:8135-45. 2003
    ....
  16. pmc Protection against electrophile and oxidant stress by induction of the phase 2 response: fate of cysteines of the Keap1 sensor modified by inducers
    Nobunao Wakabayashi
    The Lewis B and Dorothy Cullman Cancer Chemoprotection Center, Department of Pharmacology and Molecular Sciences, School of Medicine, The Johns Hopkins University, Baltimore, MD 21205, USA
    Proc Natl Acad Sci U S A 101:2040-5. 2004
    ....
  17. pmc Glutathione peroxidase 2, the major cigarette smoke-inducible isoform of GPX in lungs, is regulated by Nrf2
    Anju Singh
    Department of Environmental Health Sciences, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD 21205, USA
    Am J Respir Cell Mol Biol 35:639-50. 2006
    ..This study shows that GPX2 is the major oxidative stress-inducible cellular GPX isoform in the lungs, and that its basal as well as inducible expression is dependent on Nrf2...
  18. pmc Antioxidants enhance mammalian proteasome expression through the Keap1-Nrf2 signaling pathway
    Mi Kyoung Kwak
    Department of Environmental Health Sciences, Johns Hopkins University Bloomberg School of Public Health, Baltimore, Maryland 21205, USA
    Mol Cell Biol 23:8786-94. 2003
    ..We propose that induction of the 26S proteasome through the Nrf2 pathway represents an important indirect action of these antioxidants that can contribute to their protective effects against chronic diseases...
  19. pmc Disruption of Nrf2 enhances susceptibility to severe airway inflammation and asthma in mice
    Tirumalai Rangasamy
    Department of Environmental Health Sciences, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD 21205, USA
    J Exp Med 202:47-59. 2005
    ..Our studies suggest that the responsiveness of Nrf2-directed antioxidant pathways may act as a major determinant of susceptibility to allergen-mediated asthma...
  20. ncbi request reprint Chemoprevention through the Keap1-Nrf2 signaling pathway by phase 2 enzyme inducers
    Mi Kyoung Kwak
    Department of Environmental Health Sciences, Johns Hopkins University Bloomberg School of Public Health, 615 N Wolfe St, Baltimore, MD 21205, USA
    Mutat Res 555:133-48. 2004
    ..Rapidly accumulating data on this pathway is providing insight into the coordinated mammalian defense systems against electrophiles and oxidative stresses and the means by which it may be targeted by small molecules...
  21. ncbi request reprint Role of NRF2 in protection against hyperoxic lung injury in mice
    Hye Youn Cho
    Department of Environmental Health Sciences, The Bloomberg School of Hygiene and Public Health, Johns Hopkins University, Baltimore, Maryland, USA
    Am J Respir Cell Mol Biol 26:175-82. 2002
    ..Results demonstrated that NRF2 has a significant protective role against pulmonary hyperoxic injury in mice, possibly through transcriptional activation of lung antioxidant defense enzymes...
  22. ncbi request reprint Linkage analysis of susceptibility to hyperoxia. Nrf2 is a candidate gene
    Hye Youn Cho
    Department of Environmental Health Sciences, Johns Hopkins University, School of Public Health, Baltimore, Maryland, USA
    Am J Respir Cell Mol Biol 26:42-51. 2002
    ..Results from this study have important implications for understanding the mechanisms through which oxidants mediate the pathogenesis of lung disease...
  23. pmc Disruption of Nrf2 impairs the resolution of hyperoxia-induced acute lung injury and inflammation in mice
    Narsa M Reddy
    Department of Environmental Health Sciences, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD 21205, USA
    J Immunol 182:7264-71. 2009
    ....
  24. pmc Enhanced expression of the transcription factor Nrf2 by cancer chemopreventive agents: role of antioxidant response element-like sequences in the nrf2 promoter
    Mi Kyoung Kwak
    Department of Environmental Health Sciences, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland 21205, USA
    Mol Cell Biol 22:2883-92. 2002
    ....
  25. pmc Global mapping of binding sites for Nrf2 identifies novel targets in cell survival response through ChIP-Seq profiling and network analysis
    Deepti Malhotra
    Department of Environmental Health Sciences Department, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205, USA
    Nucleic Acids Res 38:5718-34. 2010
    ..Results were confirmed in an in vivo stress model of cigarette smoke-exposed mice. This study reveals global circuitry of the Nrf2 stress response emphasizing Nrf2 as a central node in cell survival response...
  26. ncbi request reprint Identification of Nrf2-regulated genes induced by the chemopreventive agent sulforaphane by oligonucleotide microarray
    Rajesh K Thimmulappa
    Department of Environmental Health Sciences, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MA 21205 2179, USA
    Cancer Res 62:5196-203. 2002
    ....
  27. pmc Nrf2-dependent sulfiredoxin-1 expression protects against cigarette smoke-induced oxidative stress in lungs
    Anju Singh
    Department of Environmental Health Sciences, Johns Hopkins Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD 212045, USA
    Free Radic Biol Med 46:376-86. 2009
    ..Thus, Srx1, a key Nrf2-regulated gene, contributes to protection against oxidative injury in the lung...
  28. pmc Genetic versus chemoprotective activation of Nrf2 signaling: overlapping yet distinct gene expression profiles between Keap1 knockout and triterpenoid-treated mice
    Melinda S Yates
    Department of Pharmacology and Molecular Sciences, Johns Hopkins School of Medicine, Baltimore, MD 21205, USA
    Carcinogenesis 30:1024-31. 2009
    ..Additionally, analysis of pharmacologic activation suggests that Nrf2 is the primary mediator of CDDO-Im activity, though other cell-signaling targets are also modulated following an oral dose of 30 micromol/kg...
  29. pmc Nrf2 regulates an adaptive response protecting against oxidative damage following diquat-mediated formation of superoxide anion
    William O Osburn
    Johns Hopkins University Bloomberg School of Public Health, Department of Environmental Health Sciences, Baltimore, MD, USA
    Arch Biochem Biophys 454:7-15. 2006
    ..Thus the enhanced sensitivity of N0 cells does not reflect basal differences in antioxidative capacity, but rather an impaired ability to mount an adaptive response to sustained oxidative stress...
  30. pmc Nrf2-dependent protection from LPS induced inflammatory response and mortality by CDDO-Imidazolide
    Rajesh K Thimmulappa
    Department of Environmental Health Sciences, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD, USA
    Biochem Biophys Res Commun 351:883-9. 2006
    ..Activation of Nrf2-dependent compensatory antioxidative pathways by CDDO-Im protects from LPS induced inflammatory response and mortality...
  31. ncbi request reprint Pharmacodynamic characterization of chemopreventive triterpenoids as exceptionally potent inducers of Nrf2-regulated genes
    Melinda S Yates
    Department of Environmental Health Sciences, Johns Hopkins University Bloomberg School of Public Health, Room E7541, 615 North Wolfe Street, Baltimore, MD 21205, USA
    Mol Cancer Ther 6:154-62. 2007
    ..This pharmacodynamic characterization highlights the chemopreventive promise of several synthetic triterpenoids in multiple target organs...
  32. pmc The triterpenoid CDDO-imidazolide confers potent protection against hyperoxic acute lung injury in mice
    Narsa M Reddy
    Department of Environmental Health Sciences, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland 21205, USA
    Am J Respir Crit Care Med 180:867-74. 2009
    ..Moreover, we have recently demonstrated that Nrf2-deficiency impairs the resolution of lung injury and inflammation after nonlethal hyperoxia exposure...
  33. pmc Genetic and pharmacologic evidence links oxidative stress to ventilator-induced lung injury in mice
    Srinivas Papaiahgari
    Department of Environmental Health Sciences Division of Physiology, Room E7547, 615 North Wolfe Street, Baltimore, MD 21205, USA
    Am J Respir Crit Care Med 176:1222-35. 2007
    ..Mechanical ventilation (MV) is an indispensable therapy for critically ill patients with acute lung injury and the adult respiratory distress syndrome. However, the mechanisms by which conventional MV induces lung injury remain unclear...
  34. pmc Genetic or pharmacologic amplification of nrf2 signaling inhibits acute inflammatory liver injury in mice
    William O Osburn
    Department of Environmental Health Sciences, Johns Hopkins University Bloomberg School of Public Health, Baltimore, Maryland, USA
    Toxicol Sci 104:218-27. 2008
    ..Taken together, these results clearly illustrate that targeted cytoprotection of hepatocytes through Nrf2 signaling during inflammation prevents the amplification of inflammatory responses in the liver...
  35. ncbi request reprint Chemoprevention with chlorophyllin in individuals exposed to dietary aflatoxin
    Patricia A Egner
    Department of Environmental Health Sciences, Johns Hopkins Bloomberg School of Public Health, 615 North Wolfe Street, Baltimore, MD 21205, USA
    Mutat Res 523:209-16. 2003
    ..Compliance in the intervention was outstanding and no toxicities were observed. Thus, CHL has been found to be a safe and effective agent suitable for use in individuals unavoidably exposed to aflatoxins...
  36. ncbi request reprint Chlorophyll, chlorophyllin and related tetrapyrroles are significant inducers of mammalian phase 2 cytoprotective genes
    Jed W Fahey
    Lewis B and Dorothy Cullman Cancer Chemoprotection Center, Department of Pharmacology and Molecular Sciences, School of Medicine, Johns Hopkins University, Baltimore, MD 21205 2185, USA
    Carcinogenesis 26:1247-55. 2005
    ....
  37. ncbi request reprint Interactive effects of nrf2 genotype and oltipraz on benzo[a]pyrene-DNA adducts and tumor yield in mice
    Minerva Ramos-Gomez
    Department of Environmental Health Sciences, Bloomberg School of Public Health, The Johns Hopkins University, Baltimore, MD 21202, USA
    Carcinogenesis 24:461-7. 2003
    ..g. P450 inhibition) for oltipraz can also occur in vivo in some tissues...
  38. ncbi request reprint Nrf2 as a target for cancer chemoprevention
    Xiang Yu
    Department of Pharmacology and Molecular Sciences, School of Medicine, Johns Hopkins University, Baltimore, MD 21205, USA
    Mutat Res 591:93-102. 2005
    ..Observations that nrf2-deficient mice are refractory to the protective actions of some chemopreventive agents highlight the importance of the Keap1-Nrf2-ARE signaling pathway as a molecular target for prevention...
  39. doi request reprint Quantification of urinary aflatoxin B1 dialdehyde metabolites formed by aflatoxin aldehyde reductase using isotope dilution tandem mass spectrometry
    Denise N Johnson
    Department of Environmental Health Sciences, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland 21205, USA
    Chem Res Toxicol 21:752-60. 2008
    ..This urinary detection of the alcohol products directly contributes to the goal of mass balancing the fate of the bioreactive 8,9-epoxides of AFB 1 in vivo...
  40. ncbi request reprint Phase 2 enzyme induction by the major metabolite of oltipraz
    Jacobus P Petzer
    Department of Chemistry and Biochemistry, University of Maryland, Baltimore County, 1000 Hilltop Circle, Baltimore, Maryland 21250, USA
    Chem Res Toxicol 16:1463-9. 2003
    ..From this study, it is concluded that the major metabolite of the cancer chemopreventive oltipraz is a phase 2 enzyme inducer of comparable potency that activates the ARE and initiates nuclear translocation of transcription factor Nrf 2...
  41. ncbi request reprint Genetic dissection of the Nrf2-dependent redox signaling-regulated transcriptional programs of cell proliferation and cytoprotection
    Narsa M Reddy
    Department of Environmental Health Sciences, The Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205, USA
    Physiol Genomics 32:74-81. 2007
    ..Collectively, these findings uncover an important insight into the nature of genes regulated by Nrf2-dependent redox signaling through GSH that are involved in cellular detoxification and proliferation...
  42. pmc Quantification of sulforaphane mercapturic acid pathway conjugates in human urine by high-performance liquid chromatography and isotope-dilution tandem mass spectrometry
    Patricia A Egner
    Department of Environmental Health Sciences, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland 21205, USA
    Chem Res Toxicol 21:1991-6. 2008
    ..This method determines SFN and all four SFN glutathione-derived metabolites with minimal sample preparation and will be extremely useful in understanding the role of SFN-rich foods in preventing cancer and other chronic diseases...
  43. ncbi request reprint Prospective detection of codon 249 mutations in plasma of hepatocellular carcinoma patients
    Peta E Jackson
    Johns Hopkins University, Bloomberg School of Public Health, 615 North Wolfe Street, Baltimore, MD 21205, USA
    Carcinogenesis 24:1657-63. 2003
    ..We have therefore found that pre-diagnosis biomarkers of specific p53 mutations can be measured in plasma and this suggests a paradigm for developing these markers for use in prevention and intervention trials...
  44. pmc NRF2 modulates aryl hydrocarbon receptor signaling: influence on adipogenesis
    Soona Shin
    Department of Pharmacology and Molecular Sciences, School of Medicine, The Johns Hopkins University, Baltimore, MD 21205, USA
    Mol Cell Biol 27:7188-97. 2007
    ..Ectopic expression of Ahr and dominant-positive Nrf2 in Nrf2-/- MEFs also substantially delayed differentiation. Thus, NRF2 directly modulates AHR signaling, highlighting bidirectional interactions of these pathways...
  45. ncbi request reprint Identification of aflatoxin M1-N7-guanine in liver and urine of tree shrews and rats following administration of aflatoxin B1
    Patricia A Egner
    Department of Environmental Health Sciences, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland 21205, USA
    Chem Res Toxicol 16:1174-80. 2003
    ..Bioassays indicated that the tree shrew was considerably more resistant than the rat to AFB(1) hepatocarcinogenesis, which may reflect the significant differences in metabolic profiles of the two species...
  46. pmc Cell stiffness, contractile stress and the role of extracellular matrix
    Steven S An
    Department of Environmental Health Sciences, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205, USA
    Biochem Biophys Res Commun 382:697-703. 2009
    ..These findings provide biophysical evidence that ECM differentially modulates muscle contractility and, for the first time, demonstrate a link between muscle contractility and Nrf2-directed responses...
  47. ncbi request reprint Potent protection against aflatoxin-induced tumorigenesis through induction of Nrf2-regulated pathways by the triterpenoid 1-[2-cyano-3-,12-dioxooleana-1,9(11)-dien-28-oyl]imidazole
    Melinda S Yates
    Johns Hopkins University, Baltimore, Maryland, USA
    Cancer Res 66:2488-94. 2006
    ..The unparalleled potency of CDDO-Im in vivo highlights the chemopreventive promise of targeting Nrf2 pathways with triterpenoids...
  48. ncbi request reprint Induction of phase 2 enzymes by serum oxidized polyamines through activation of Nrf2: effect of the polyamine metabolite acrolein
    Mi Kyoung Kwak
    Department of Environmental Health Sciences, Johns Hopkins University, Bloomberg School of Public Health, 615 N Wolfe St, Baltimore, MD 21205, USA
    Biochem Biophys Res Commun 305:662-70. 2003
    ..These results indicate that spermidine and spermine increase the expression of phase 2 genes in cells grown in culture through activation of the Nrf2-ARE pathway by generating the sulfhydryl reactive aldehyde, acrolein...
  49. pmc Innate immunity against bacterial infection following hyperoxia exposure is impaired in NRF2-deficient mice
    Narsa M Reddy
    Department of Environmental Health Sciences, Johns Hopkins Bloomberg School of Public Health, Room E7610, 615 North Wolfe Street, Baltimore, Maryland 21205, USA
    J Immunol 183:4601-8. 2009
    ..Thus, loss of Nrf2 impairs lung innate immunity and promotes susceptibility to bacterial infection after hyperoxia exposure, ultimately leading to death of the host...
  50. ncbi request reprint Protective interventions to prevent aflatoxin-induced carcinogenesis in developing countries
    John D Groopman
    Department of Environmental Health Sciences, Johns Hopkins University, Bloomberg School of Public Health, Baltimore, MD 21205, USA
    Annu Rev Public Health 29:187-203. 2008
    ..Therefore, many diverse and appropriate strategies for disease prevention are needed to decrease the incidence of aflatoxin carcinogenesis in developing countries...
  51. ncbi request reprint Prevention of liver cancer
    Kathryn Z Guyton
    Department of Environmental Health Sciences, Bloomberg School of Public Health, Johns Hopkins University, 615 North Wolfe Street, Baltimore, MD 21205 2179, USA
    Curr Oncol Rep 4:464-70. 2002
    ..These include genes and gene products controlling viral replication, carcinogen metabolism, signal transduction, cell-cycle arrest, apoptosis, proliferation, and oxidative stress...
  52. pmc Regulation of notch1 signaling by nrf2: implications for tissue regeneration
    Nobunao Wakabayashi
    Department of Environmental Health Sciences, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD 21205, USA
    Sci Signal 3:ra52. 2010
    ..We report a functional role for this cross talk between the two pathways and show that disruption of Nrf2 impeded liver regeneration after partial hepatectomy and was rescued by reestablishment of Notch1 signaling...
  53. ncbi request reprint Conceptually new low-calcemic oxime analogues of the hormone 1 alpha,25-dihydroxyvitamin D(3): synthesis and biological testing
    Gary H Posner
    Department of Chemistry, School of Arts and Sciences, The Johns Hopkins University, Baltimore, Maryland 21218, USA
    J Med Chem 45:1723-30. 2002
    ..In terms of in vivo toxicity (hypercalcemia), ketone 2b is strongly calcemic in rats, whereas oxime 3b and oxime ether 4b are considerably less calcemic (i.e., safer) than calcitriol (1)...
  54. pmc Deficiency in Nrf2-GSH signaling impairs type II cell growth and enhances sensitivity to oxidants
    Narsa M Reddy
    The Johns Hopkins Bloomberg School of Public Health, Department of Environmental Health Sciences, 615 North Wolfe Street, Baltimore, MD 21205, USA
    Am J Respir Cell Mol Biol 37:3-8. 2007
    ..Our data suggest that dysfunctional Nrf2-regulated GSH-induced signaling is associated with deregulation of type II cell proliferation, which contributes to abnormal injury and repair and leads to respiratory impairment...
  55. ncbi request reprint Aflatoxin and hepatitis B virus biomarkers: a paradigm for complex environmental exposures and cancer risk
    John D Groopman
    Johns Hopkins University, Bloomberg School of Public Health, Department of Environmental Health Sciences, 615 North Wolfe Street, Baltimore, MD 21205, USA
    Cancer Biomark 1:5-14. 2005
    ..This systematic approach provides encouragement for preventive interventions and should serve as a template for the development, validation and application of other chemical-specific biomarkers to cancer or other chronic diseases...
  56. pmc Divergent responses of chondrocytes and endothelial cells to shear stress: cross-talk among COX-2, the phase 2 response, and apoptosis
    Zachary R Healy
    Department of Chemical and Biomolecular Engineering, The Johns Hopkins University, Baltimore, MD 21218, USA
    Proc Natl Acad Sci U S A 102:14010-5. 2005
    ....
  57. ncbi request reprint Role of metabolism and viruses in aflatoxin-induced liver cancer
    John D Groopman
    Department of Environmental Health Sciences, The Johns Hopkins University, Bloomberg School of Public Health, 615 North Wolfe Street, Baltimore, MD 21205, USA
    Toxicol Appl Pharmacol 206:131-7. 2005
    ..This systematic approach provides encouragement for preventive interventions and should serve as a template for the development, validation and application of other chemical-specific biomarkers to cancer or other chronic diseases...
  58. ncbi request reprint Quantification of aflatoxin-B1-N7-Guanine in human urine by high-performance liquid chromatography and isotope dilution tandem mass spectrometry
    Patricia A Egner
    Department of Environmental Health Sciences, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland 21205, USA
    Chem Res Toxicol 19:1191-5. 2006
    ....
  59. pmc Specific mutations of hepatitis B virus in plasma predict liver cancer development
    Shuang Yuan Kuang
    Bloomberg School of Public Health, Johns Hopkins University, 615 North Wolfe Street, Baltimore, MD 21205, USA
    Proc Natl Acad Sci U S A 101:3575-80. 2004
    ..022, two-tailed). We therefore found that a prediagnosis biomarker of specific HBV mutations can be measured in plasma and suggest this marker for use as an intermediate endpoint in prevention and intervention trials...
  60. ncbi request reprint Quantitative analysis and chronic dosimetry of the aflatoxin B1 plasma albumin adduct Lys-AFB1 in rats by isotope dilution mass spectrometry
    Peter F Scholl
    Department of Environmental Health Sciences, Bloomberg School of Public Health, Johns Hopkins University, 615 North Wolfe Street, Baltimore, Maryland 21205 2103, USA
    Chem Res Toxicol 19:44-9. 2006
    ....
  61. ncbi request reprint Assessing the effect of interventions in the context of mixture distributions with detection limits
    Haitao Chu
    Department of Epidemiology, Bloomberg School of Public Health, Johns Hopkins University, 615 N Wolfe Street, Baltimore, MD 21205, U S A
    Stat Med 24:2053-67. 2005
    ..We illustrate our methods using data from a randomized clinical trial conducted in Qidong, People's Republic of China...
  62. pmc Nrf2 signaling: an adaptive response pathway for protection against environmental toxic insults
    William O Osburn
    Johns Hopkins University Bloomberg School of Public Health, Department of Environmental Health Sciences, 615 North Wolfe Street, Baltimore, MD 21205, USA
    Mutat Res 659:31-9. 2008
    ....
  63. pmc Formation of two novel estrogen guanine adducts and HPLC/MS detection of 4-hydroxyestradiol-N7-guanine in human urine
    Leslie A Bransfield
    Department of Chemistry, Zanvyl Krieger School of Arts and Sciences, Johns Hopkins University, Baltimore, Maryland 21218, USA
    Chem Res Toxicol 21:1622-30. 2008
    ....
  64. ncbi request reprint Chemoprevention by 1,2-dithiole-3-thiones through induction of NQO1 and other phase 2 enzymes
    Mi Kyoung Kwak
    Department of Environmental Health Sciences, School of Public Health Sciences, Johns Hopkins University Bloomberg, Baltimore, Maryland 21205, USA
    Methods Enzymol 382:414-23. 2004
  65. ncbi request reprint Increased colonic inflammatory injury and formation of aberrant crypt foci in Nrf2-deficient mice upon dextran sulfate treatment
    William O Osburn
    Department of Environmental Health Sciences, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD 21205, USA
    Int J Cancer 121:1883-91. 2007
    ..Taken together, these results clearly illustrate the role of Nrf2 in regulating an adaptive response that protects against early-phase inflammation-mediated tumorigenesis...
  66. ncbi request reprint In vivo modulation of the Parkinsonian phenotype by Nrf2
    Neal C Burton
    Department of Environmental Health Sciences, Johns Hopkins University, Bloomberg School of Public Health, Baltimore, MD 21205, USA
    Neurotoxicology 27:1094-100. 2006
    ..The in vivo activation of the Nrf2 pathway in the brain may be an important strategy to mitigate the effects of oxidative stress in neurodegenerative disorders and neurological disease...
  67. pmc Role of dietary supplements/nutraceuticals in chemoprevention through induction of cytoprotective enzymes
    Jed W Fahey
    Department of Pharmacology, International Health, and Environmental Health Sciences, Johns Hopkins University, Baltimore, Maryland 21205, USA
    Chem Res Toxicol 20:572-6. 2007
  68. pmc Targeting Nrf2 with the triterpenoid CDDO-imidazolide attenuates cigarette smoke-induced emphysema and cardiac dysfunction in mice
    Thomas E Sussan
    Department of Environmental Health Sciences, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD 21205, USA
    Proc Natl Acad Sci U S A 106:250-5. 2009
    ..These results suggest that targeting the Nrf2 pathway during the etiopathogenesis of emphysema may represent an important approach for prophylaxis against COPD...
  69. pmc Nrf2 is a critical regulator of the innate immune response and survival during experimental sepsis
    Rajesh K Thimmulappa
    Department of Environmental Health Sciences, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland 21205, USA
    J Clin Invest 116:984-95. 2006
    ..Our study reveals Nrf2 as a novel modifier gene of sepsis that determines survival by mounting an appropriate innate immune response...
  70. pmc Bioavailability of Sulforaphane from two broccoli sprout beverages: results of a short-term, cross-over clinical trial in Qidong, China
    Patricia A Egner
    Department of Environmental Health Sciences, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD, USA
    Cancer Prev Res (Phila) 4:384-95. 2011
    ..Cancer Prev Res; 4(3); 384-95. ©2011 AACR...
  71. pmc A novel acetylenic tricyclic bis-(cyano enone) potently induces phase 2 cytoprotective pathways and blocks liver carcinogenesis induced by aflatoxin
    Karen Liby
    Dartmouth Medical School, Hanover, NH 03755, USA
    Cancer Res 68:6727-33. 2008
    ....
  72. ncbi request reprint Induction of NAD(P)H quinone oxidoreductase by vegetables widely consumed in Catalonia, Spain
    Nuria Laso
    Departamento de Farmacologia y Quimica Terapeutica, IDIBAPS, Facultad de Medicina, Universidad de Barcelona, Spain
    Nutr Cancer 52:49-58. 2005
    ..These results are very similar to those described for vegetables consumed in the United States, with the exception of calcot, which is common in Catalonia but is not grown or consumed widely in the United States...
  73. ncbi request reprint Natural chlorophyll inhibits aflatoxin B1-induced multi-organ carcinogenesis in the rat
    Michael T Simonich
    Linus Pauling Institute, Oregon State University, Corvallis, OR 97331, USA
    Carcinogenesis 28:1294-302. 2007
    ..0026) and 75% (P = 0.0004), respectively. These results show Chl and CHL provide potent chemoprotection against early biochemical and late pathophysiological biomarkers of AFB(1) carcinogenesis in the rat liver and colon...
  74. ncbi request reprint Acceleration to death from liver cancer in people with hepatitis B viral mutations detected in plasma by mass spectrometry
    Jian Guo Chen
    Qidong Liver Cancer Institute, Qidong, Jiangsu Province, People s Republic of China
    Cancer Epidemiol Biomarkers Prev 16:1213-8. 2007
    ..04 for age 35 years to 1.0 for age 65 years with the 90% confidence band being above 1 for ages < 50 years. These findings provide a conceptual framework to explain the acceleration of mortality in individuals infected with HBV...
  75. ncbi request reprint Multiple comparisons model-based clustering and ternary pattern tree numerical display of gene response to treatment: procedure and application to the preclinical evaluation of chemopreventive agents
    Thomas R Sutter
    W Harry Feinstone Center for Genomic Research, University of Memphis, Memphis, Tennessee 38152, USA
    Mol Cancer Ther 1:1283-92. 2002
    ..Also, small treatment-specific subsets of genes were identified that may be indicative of additional pharmacophores present in the test compounds...
  76. ncbi request reprint Hepatocyte-specific deletion of the keap1 gene activates Nrf2 and confers potent resistance against acute drug toxicity
    Hiromi Okawa
    Graduate School of Comprehensive Human Sciences, Center for Tsukuba Advanced Research Alliance, University of Tsukuba, 1 1 1 Tennoudai, Tsukuba 305 8577, Japan
    Biochem Biophys Res Commun 339:79-88. 2006
    ..These results demonstrate that chronic activation of Nrf2 confers animals with resistance to xenobiotics without affecting the morphological and physiological integrity of hepatocytes...
  77. ncbi request reprint Identification of novel transcriptional networks in response to treatment with the anticarcinogen 3H-1,2-dithiole-3-thione
    Yong Huang
    W Harry Feinstone Center for Genomic Research, University of Memphis, Memphis, Tennessee 38152, USA
    Physiol Genomics 24:144-53. 2006
    ..000331) pathways. These findings showed a profound impact of D3T on lipid metabolism and anti-inflammatory/immune-suppressive response, indicating a broader cytoprotective effect of this compound than previously expected...
  78. ncbi request reprint Induction of Nrf2-regulated genes by 3H-1, 2-dithiole-3-thione through the ERK signaling pathway in murine keratinocytes
    Sarala Manandhar
    College of Pharmacy, Yeungnam University, 214 1 Dae Dong, Gyeongsan si, Gyeongsangbuk do 712 749, South Korea
    Eur J Pharmacol 577:17-27. 2007
    ....
  79. ncbi request reprint Evaluation of the cancer chemopreventive potency of dithiolethione analogs of oltipraz
    B D Roebuck
    Department of Pharmacology and Toxicology, Dartmouth Medical School, Hanover, NH 03755, USA
    Carcinogenesis 24:1919-28. 2003
    ..While efficacy in humans has yet to be tested, D3T is clearly more potent than oltipraz and serves as a useful molecular probe for determining the key events associated with protection by this class of agents...
  80. ncbi request reprint Oltipraz chemoprevention trial in Qidong, People's Republic of China: unaltered oxidative biomarkers
    Bente Glintborg
    Department of Clinical Pharmacology Q7642, H S Rigshospitalet, Tagensvej 20, Copenhagen, Denmark
    Free Radic Biol Med 41:1010-4. 2006
    ..Mechanisms other than prevention of oxidative DNA damage may be of higher importance when oltipraz is used as a chemopreventive agent in humans...
  81. ncbi request reprint The importance of carcinogen dose in chemoprevention studies: quantitative interrelationships between, dibenzo[a,l]pyrene dose, chlorophyllin dose, target organ DNA adduct biomarkers and final tumor outcome
    M Margaret Pratt
    Department of Environmental and Molecular Toxicology, Oregon State University, Corvallis, OR 97339, USA
    Carcinogenesis 28:611-24. 2007
    ....
  82. ncbi request reprint The transcriptional response to a peroxisome proliferator-activated receptor alpha agonist includes increased expression of proteome maintenance genes
    Steven P Anderson
    Investigative Toxicology and Pathology Group, Safety Assessment, GlaxoSmithKline Research and Development, Research Triangle Park, North Carolina 27709, USA
    J Biol Chem 279:52390-8. 2004
    ....
  83. ncbi request reprint Mimetics of caloric restriction include agonists of lipid-activated nuclear receptors
    J Christopher Corton
    Toxicogenomics, Chapel Hill, North Carolina 27514, USA
    J Biol Chem 279:46204-12. 2004
    ..These results demonstrate that PPARalpha mediates some of the effects of CR and indicate that a pharmacological approach to mimicking many of the beneficial effects of CR may be possible...

Research Grants35

  1. MOLECULAR MECHANISMS OF CHEMOPREVENTION--DITHIOLETHIONES
    Thomas Kensler; Fiscal Year: 2003
    ..The long-term goal of this project is to facilitate the most efficient and effective use dithiolethiones as protective agents in human populations exposed to environmental toxicants. ..
  2. Chemopreventive Efficacy of Broccoli Sprouts in Humans
    Thomas Kensler; Fiscal Year: 2004
    ..abstract_text> ..
  3. Protection by Induction of Ubiquitin-Proteasome Systems
    Thomas Kensler; Fiscal Year: 2005
    ....
  4. Role of Enzyme Induction in Cancer Chemoprevention
    Thomas Kensler; Fiscal Year: 2006
    ....
  5. Molecular Mechanisms of Chemoprevention: Dithiolethiones
    Thomas Kensler; Fiscal Year: 2007
    ..Collectively, these studies will further the goal of effectively using dithiolethiones as protective agents in human populations exposed to environmental toxicants. ..
  6. Role of Enzyme Induction in Cancer Chemoprevention
    Thomas Kensler; Fiscal Year: 2007
    ....
  7. Role of Enzyme Induction in Cancer Chemoprevention
    Thomas Kensler; Fiscal Year: 2009
    ..abstract_text> ..
  8. MECHANISMS OF ANTICARCINOGENESIS BY DITHIOLTHIONES
    Thomas Kensler; Fiscal Year: 1993
    ..The long term goal of this work is to facilitate our understanding of how dietary constituents may modulate the target organ risk in human populations exposed to naturally-occurring carcinogens...
  9. Molecular Mechanisms of Chemoprevention: NRF2 Signaling
    Thomas Kensler; Fiscal Year: 2009
    ....