Research Topics
| P TalalaySummaryAffiliation: Johns Hopkins University Country: USA Publications
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Publications
Sulforaphane mobilizes cellular defenses that protect skin against damage by UV radiationPaul Talalay
Department of Pharmacology and Molecular Sciences, Bloomberg School of Public Health, The Johns Hopkins University, Baltimore, MD 21205, USA
Proc Natl Acad Sci U S A 104:17500-5. 2007..7% (range 8.37-78.1%; P = 0.025). This protection against a carcinogen in humans is catalytic and long lasting...
A fascination with enzymes: the journey not the arrival mattersPaul Talalay
Lewis B. and Dorothy Cullman Cancer Chemoprotection Center, Department of Pharmacology and Molecular Sciences, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
J Biol Chem 280:28829-47. 2005
Importance of phase 2 gene regulation in protection against electrophile and reactive oxygen toxicity and carcinogenesisPaul Talalay
Department of Pharmacology and Molecular Sciences, School of Medicine, Johns Hopkins University, Baltimore, MD 21205, USA
Adv Enzyme Regul 43:121-34. 2003
Phytochemicals from cruciferous plants protect against cancer by modulating carcinogen metabolismP Talalay
Department of Pharmacology and Molecular Sciences, School of Medicine, Johns Hopkins University, Baltimore, MD 21205, USA
J Nutr 131:3027S-33S. 2001..Thus, in addition to detoxifying electrophiles, these proteins exercise versatile, long-lasting and catalytic antioxidant protection...
Chemoprotection against cancer by induction of phase 2 enzymesP Talalay
Department of Pharmacology and Molecular Sciences, The Johns Hopkins Universit, School of Medicine, Baltimore, MD 21205, USA
Biofactors 12:5-11. 2000....
Sensitivity to carcinogenesis is increased and chemoprotective efficacy of enzyme inducers is lost in nrf2 transcription factor-deficient miceM Ramos-Gomez
Department of Environmental Health Sciences, The Johns Hopkins University, Baltimore, MD 21205, USA
Proc Natl Acad Sci U S A 98:3410-5. 2001..Moreover, the total loss of anticarcinogenic efficacy of oltipraz in the nrf2-disrupted mice highlights the prime importance of elevated phase 2 gene expression in chemoprotection by this and similar enzyme inducers...
Crystal structure of human quinone reductase type 2, a metalloflavoproteinC E Foster
Department of Biophysics, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA
Biochemistry 38:9881-6. 1999..Two histidine nitrogens, one cysteine thiol, and a main chain carbonyl group are involved in metal coordination. The metal binding site is solvent-accessible, and is separated from the FAD cofactor by a distance of about 13 A...
Potency of Michael reaction acceptors as inducers of enzymes that protect against carcinogenesis depends on their reactivity with sulfhydryl groupsA T Dinkova-Kostova
Department of Pharmacology, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
Proc Natl Acad Sci U S A 98:3404-9. 2001..Surprisingly, these ortho-hydroxyl groups display a propensity for extensive intermolecular hydrogen bond formation, which may raise the reactivity and facilitate addition of mercaptans, thereby raising inducer potencies...
Identification of a common chemical signal regulating the induction of enzymes that protect against chemical carcinogenesisP Talalay
Department of Pharmacology and Molecular Science, Johns Hopkins University School of Medicine, Baltimore, MD 21205
Proc Natl Acad Sci U S A 85:8261-5. 1988....
Unexpected genetic and structural relationships of a long-forgotten flavoenzyme to NAD(P)H:quinone reductase (DT-diaphorase)Q Zhao
Department of Pharmacology and Molecular Sciences, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
Proc Natl Acad Sci U S A 94:1669-74. 1997..In the absence of this binding site in QR2, the enzyme retains the essential catalytic machinery, including affinity for FAD, but cannot bind phosphorylated hydride donors...
Chemoprotective glucosinolates and isothiocyanates of broccoli sprouts: metabolism and excretion in humansT A Shapiro
Department of Pharmacology and Molecular Sciences, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA
Cancer Epidemiol Biomarkers Prev 10:501-8. 2001..These findings will assist in the design of dosing regimens for clinical studies of broccoli sprout efficacy...
Structures of recombinant human and mouse NAD(P)H:quinone oxidoreductases: species comparison and structural changes with substrate binding and releaseM Faig
Departments of Biophysics and Biophysical Chemistry and Pharmacology and Molecular Sciences, Johns Hopkins Medical School, Baltimore, MD 21205, USA
Proc Natl Acad Sci U S A 97:3177-82. 2000..In the human QR1-duroquinone structure one ring carbon is significantly closer to the flavin N5, suggesting a direct hydride transfer to this atom...
Induction of phase 2 genes by sulforaphane protects retinal pigment epithelial cells against photooxidative damageXiangqun Gao
Lewis B. and Dorothy Cullman Cancer Chemoprotection Center, Department of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
Proc Natl Acad Sci U S A 101:10446-51. 2004..Moreover, the finding that dietary inducers provide indirect antioxidant protection suggests novel strategies for preventing chronic degenerative diseases, such as age-related macular degeneration...
Chlorophyll, chlorophyllin and related tetrapyrroles are significant inducers of mammalian phase 2 cytoprotective genesJed 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....
Sulforaphane inhibits extracellular, intracellular, and antibiotic-resistant strains of Helicobacter pylori and prevents benzo[a]pyrene-induced stomach tumorsJed W Fahey
Lewis B and Dorothy Cullman Cancer Chemoprotection Center, Department of Pharmacology and Molecular Sciences, The Johns Hopkins University School of Medicine, 725 North Wolfe Street, Baltimore, MD 21205 2185, USA
Proc Natl Acad Sci U S A 99:7610-5. 2002....
Dietary amelioration of Helicobacter pylori infection: design criteria for a clinical trialJed W Fahey
Department of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, 725 North Wolfe Street, 406 WBSB, Baltimore, MD 21205 2185, USA
Cancer Epidemiol Biomarkers Prev 13:1610-6. 2004..For the least variable quartile, as few as 12 subjects would be needed; for the most variable quartile, at least 147 subjects would be required in each arm...
Direct and indirect antioxidant properties of inducers of cytoprotective proteinsAlbena T Dinkova-Kostova
Division of Clinical Pharmacology, Department of Medicine, The Johns Hopkins University School ofMedicine, Baltimore, MD, USA
Mol Nutr Food Res 52:S128-38. 2008....
The chemical diversity and distribution of glucosinolates and isothiocyanates among plantsJ W Fahey
Department of Pharmacology and Molecular Sciences, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
Phytochemistry 56:5-51. 2001....
Powerful and prolonged protection of human retinal pigment epithelial cells, keratinocytes, and mouse leukemia cells against oxidative damage: the indirect antioxidant effects of sulforaphaneX Gao
Lewis B. and Dorothy Cullman Cancer Chemoprotection Center, and Department of Pharmacology and Molecular Sciences, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
Proc Natl Acad Sci U S A 98:15221-6. 2001..It is therefore highly likely that the multifaceted and prolonged antioxidant protection provided by sulforaphane is a general phenomenon that is mediated through induction of the Phase 2 enzyme response...
Preclinical and clinical evaluation of sulforaphane for chemoprevention in the breastBrian S Cornblatt
Department of Environmental Health Sciences, Johns Hopkins University Bloomberg School of Public Health, 615 North Wolfe Street, Baltimore, MD 21205, USA
Carcinogenesis 28:1485-90. 2007..These findings provide a strong rationale for evaluating the protective effects of a broccoli sprout preparation in clinical trials of women at risk for breast cancer...
Precise determination of the erythema response of human skin to ultraviolet radiation and quantification of effects of protectorsZachary R Healy
Department of Pharmacology and Molecular Sciences, Lewis B and Dorothy Cullman Cancer Chemoprotection Center, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
Photodermatol Photoimmunol Photomed 25:45-50. 2009..These methods have permitted evaluation of the efficacy of protectors, such as sulforaphane from crucifers, that defend cells through induction of cytoprotective (phase 2) genes...
Protection against electrophile and oxidative stress by induction of phase 2 genes: the quest for the elusive sensor that responds to inducersW David Holtzclaw
The Lewis B. and Dorothy Cullman Cancer Chemoprotection Center, Department of Pharmacology and Molecular Sciences, School of Medicine, Johns Hopkins University, Baltimore, MD 21205, USA
Adv Enzyme Regul 44:335-67. 2004
Protection against UV-light-induced skin carcinogenesis in SKH-1 high-risk mice by sulforaphane-containing broccoli sprout extractsAlbena T Dinkova-Kostova
The Lewis B. and Dorothy Cullman Cancer Chemoprotection Center, Department of Pharmacology and Molecular Sciences, School of Medicine, Johns Hopkins University, 725 N. Wolfe Street, Baltimore, MD 21205, USA
Cancer Lett 240:243-52. 2006..Thus, topical application of sulforaphane-containing broccoli sprout extracts is a promising strategy for protecting against skin tumor formation after exposure to UV radiation...
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 ChinaThomas 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...
Enzymatic and nonenzymatic polarizations of alpha,beta-unsaturated ketosteroids and phenolic steroids. Implications for the roles of hydrogen bonding in the catalytic mechanism of delta 5-3-ketosteroid isomeraseQ Zhao
Department of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205
Biochemistry 34:426-34. 1995..0 nm, while the corresponding 4-methyl ether, 4-methoxyandrost-4-ene-3,17-dione, which cannot form an internal hydrogen bond, shows a lambda max of 258.5 nm in aqueous solution.(ABSTRACT TRUNCATED AT 250 WORDS)..
Induction of the phase 2 response in mouse and human skin by sulforaphane-containing broccoli sprout extractsAlbena T Dinkova Kostova
Department of Pharmacology and Molecular Sciences, School of Medicine, Johns Hopkins University, 725 North Wolfe Street, Baltimore, MD 21205, USA
Cancer Epidemiol Biomarkers Prev 16:847-51. 2007..5- and 4.5-fold after application of 150 nmol doses, once or three times (at 24 h-intervals), respectively, thus providing direct evidence for induction of the phase 2 response in humans...
Extremely potent triterpenoid inducers of the phase 2 response: correlations of protection against oxidant and inflammatory stressAlbena T Dinkova-Kostova
The Lewis B. and Dorothy Cullman Cancer Chemoprotection Center, Department of Pharmacology and Molecular Sciences, School of Medicine, Johns Hopkins University, 725 North Wolfe Street, Baltimore, MD 21205, USA
Proc Natl Acad Sci U S A 102:4584-9. 2005..91) over 6 orders of magnitude of concentration. Thus, in addition to blocking inflammation and promoting differentiation, these TP exhibit another very important protective property: the induction of the phase 2 response...
Direct evidence that sulfhydryl groups of Keap1 are the sensors regulating induction of phase 2 enzymes that protect against carcinogens and oxidantsAlbena T Dinkova-Kostova
The Lewis B and Dorothy Cullman Cancer Chemoprotection Center, Department of Pharmacology and Molecular Sciences, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
Proc Natl Acad Sci U S A 99:11908-13. 2002..These residues are located in the intervening region between BTB and Kelch repeat domains of Keap1 and probably are the direct sensors of inducers of the phase 2 system...
Protection against electrophile and oxidant stress by induction of the phase 2 response: fate of cysteines of the Keap1 sensor modified by inducersNobunao 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....
Safety, tolerance, and metabolism of broccoli sprout glucosinolates and isothiocyanates: a clinical phase I studyTheresa A Shapiro
Division of Clinical Pharmacology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
Nutr Cancer 55:53-62. 2006..No significant or consistent subjective or objective abnormal events (toxicities) associated with any of the sprout extract ingestions were observed...
Phenolic Michael reaction acceptors: combined direct and indirect antioxidant defenses against electrophiles and oxidantsA T Dinkova-Kostova
The Lewis B and Dorothy Cullman Cancer Chemoprotection Center, Department of Pharmacology, and Moleclar Sciences, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA
Med Chem 3:261-8. 2007..e., acting indirectly, but with much more diverse and long-lasting effects...
The three-dimensional structure of NAD(P)H:quinone reductase, a flavoprotein involved in cancer chemoprotection and chemotherapy: mechanism of the two-electron reductionR Li
Department of Biophysics and Biophysical Chemistry, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
Proc Natl Acad Sci U S A 92:8846-50. 1995....
Electrophilic tuning of the chemoprotective natural product sulforaphaneYoung Hoon Ahn
Department of Pharmacology and Molecular Sciences, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
Proc Natl Acad Sci U S A 107:9590-5. 2010..We further show in living cells that a sulfoxythiocarbamate analog can label Keap1 on several key cysteine residues as well as other cellular proteins offering new insights into the mechanism of chemoprotection...
A dicyanotriterpenoid induces cytoprotective enzymes and reduces multiplicity of skin tumors in UV-irradiated miceAlbena T Dinkova-Kostova
The Lewis B and Dorothy Cullman Cancer Chemoprotection Center, Department of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, 725 N Wolfe Street, WBSB Room 406, Baltimore, MD 21205, USA
Biochem Biophys Res Commun 367:859-65. 2008....
Quantitative determination of dithiocarbamates in human plasma, serum, erythrocytes and urine: pharmacokinetics of broccoli sprout isothiocyanates in humansLingxiang Ye
Department of Pharmacology and Molecular Sciences, The Johns Hopkins University School of Medicine, 725 N. Wolfe Street, Baltimore, MD 21205, USA
Clin Chim Acta 316:43-53. 2002....
Reprogramming of keratin biosynthesis by sulforaphane restores skin integrity in epidermolysis bullosa simplexMichelle L Kerns
Department of Biological Chemistry, 725 North Wolfe Street, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
Proc Natl Acad Sci U S A 104:14460-5. 2007..Nrf2 induction is brought about by treatment with sulforaphane, a natural product. Sulforaphane thus represents an attractive option for the prevention of skin blistering associated with K14 mutations in EBS...
Dietary glucoraphanin-rich broccoli sprout extracts protect against UV radiation-induced skin carcinogenesis in SKH-1 hairless miceAlbena T Dinkova-Kostova
The Lewis B and Dorothy Cullman Cancer Chemoprotection Center, Department of Pharmacology and Molecular Sciences, School of Medicine, Johns Hopkins University, Baltimore, Maryland 21205, USA
Photochem Photobiol Sci 9:597-600. 2010....
Role of nicotinamide quinone oxidoreductase 1 (NQO1) in protection against toxicity of electrophiles and reactive oxygen intermediatesPaul Talalay
Department of Pharmacology and Molecular Science, Lewis B. and Dorothy Cullman Cancer Center Chemoprotection Center, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
Methods Enzymol 382:355-64. 2004
Divergent responses of chondrocytes and endothelial cells to shear stress: cross-talk among COX-2, the phase 2 response, and apoptosisZachary 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....
Inactivation of tautomerase activity of macrophage migration inhibitory factor by sulforaphane: a potential biomarker for anti-inflammatory interventionZachary R Healy
The Lewis B and Dorothy Cullman Cancer Chemoprotection Center, Department of Pharmacology and Molecular Sciences, Johns Hopkins School of Medicine, Baltimore, MD 21205, USA
Cancer Epidemiol Biomarkers Prev 20:1516-23. 2011..A simple rapid method for determining this activity in tissues and body fluids may therefore be valuable for assessing severity of inflammation and efficacy of intervention...
The "Prochaska" microtiter plate bioassay for inducers of NQO1Jed W Fahey
Department of Pharmacology and Molecular Science, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA
Methods Enzymol 382:243-58. 2004
Chemical structures of inducers of nicotinamide quinone oxidoreductase 1 (NQO1)Albena T Dinkova-Kostova
Department of Pharmacology and Molecular Science, Lewis B. and Dorothy Cullman Cancer Center Chemoprotection Center, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
Methods Enzymol 382:423-48. 2004
Coordinate regulation of enzyme markers for inflammation and for protection against oxidants and electrophilesHua Liu
Lewis B and Dorothy Cullman Cancer Chemoprotection Center, Department of Pharmacology and Molecular Sciences, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
Proc Natl Acad Sci U S A 105:15926-31. 2008..These studies identify suppression of inflammation as a consistent property of inducers of the phase 2 response and strongly suggest that this property is a central aspect of their chemoprotective actions...
Rapid body weight gain increases the risk of UV radiation-induced skin carcinogenesis in SKH-1 hairless miceAlbena T Dinkova-Kostova
Department of Pharmacology and Molecular Sciences, Johns Hopkins University, Baltimore, MD 21205, USA
Nutr Res 28:539-43. 2008..Considering the escalating numbers of individuals worldwide who are overweight or obese, our findings provide further impetus for advocating healthier diets and maintenance of constant body weight in adults...
Redox ranking of inducers of a cancer-protective enzyme via the energy of their highest occupied molecular orbitalVincent Zoete
Laboratoire de Chimie Biophysique, , ISIS, CNRS UMR 7006, Strasbourg, France
Free Radic Biol Med 36:1418-23. 2004....
Novel semisynthetic analogues of betulinic acid with diverse cytoprotective, antiproliferative, and proapoptotic activitiesKaren Liby
Dartmouth Medical School, Hanover, NH 03755, USA
Mol Cancer Ther 6:2113-9. 2007..These results suggest that BA is a useful platform for drug development, and the enhanced potency and varied biological activities of CBA-Im make it a promising candidate for further chemoprevention or chemotherapeutic studies...
Harnessing the anticancer power of plantsPaul Talalay
Laboratory for Molecular Sciences, Johns Hopkins University School of Medicine, USA
Johns Hopkins Med Lett Health After 50 14:6. 2002
Two-step mechanism of induction of the gene expression of a prototypic cancer-protective enzyme by diphenolsRené V Bensasson
Laboratoire de Chimie des Substances Naturelles, MNHN, USM 0502 UMR 5154 CNRS, Case 54, 63 rue Buffon, F 75005 Paris, France
Chem Res Toxicol 21:805-12. 2008....
Research Grants
- Isolation & Evaluation of Anticarcinogenic GlucosinolatePaul Talalay; Fiscal Year: 2005..These pharmacokinetic studies will set the stage for the development of safe and effective dietary chemoprotectors for human use. ..
- Isolation and Evaluation of Anticarcinogenic GlucosinolatesPaul Talalay; Fiscal Year: 2009..We will isolate these components in adequate quantities for evaluation in animals and humans, and formulate appropriate recommendations to achieve disease risk reduction in humans. ..
- Isolation and Evaluation of Anticarcinogenic GlucosinolatesPaul Talalay; Fiscal Year: 2010..We will isolate these components in adequate quantities for evaluation in animals and humans, and formulate appropriate recommendations to achieve disease risk reduction in humans. ..
