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Dr. Lijiang Song

Associate Professor - Head of Mass Spectrometry Facility


My research is focused on mass spectrometry based metabolomics and proteomics, their applications in areas including natural product drug discovery, drug metabolism, disease biomarker discovery and environmental analysis.

lijiang dot song at warwick dot ac dot uk

02476 1 51766

Office A1.08

Office hours: 8am-6pm, Mon-Fri

Groups at Warwick


Affiliations

Department of Chemistry


Biography

  • 2002-2005, PDRA, Department of Biological Sciences, Essex University
  • 2005-2008, PDRA, Department of Chemistry, University of Warwick
  • 2013-2014, Head of Clinical Pharmacology Lab, Department of Tropical Medicine, University of Oxford
  • 2008-current, Head of Mass spectrometry, Department of Chemistry, University of Warwick

I am working on the following projects at the moment:

  • Nucleoside decoys - metabolic interference in plant self defence (funded by BBSRC)

  • Save the ashes, potential biomarker discovery for ash die back (funded by BBSRC)
  • Bioactive natural product discovery from marine actinomycetes (funded by the Royal Society)
  • Antimicrobial resistance in the environment and its relationship with pharmaceutical industrial waste (funded by NERC)

My research is focused on mass spectrometry based metabolomics and proteomics, their applications in areas including natural product drug discovery, drug metabolism, disease biomarker discovery and environmental analysis.

1. Bioactive natural product discovery from microorganism and plant, using a combination of liquid chromatography, high reoslution high accuracy MS, MS/MS, 1D and 2D NMR techniques, we carry out dereplication, identification, purification and structure elucidation of novel bioactive natural products.

2. Drug mechanism of action and metabolism analysis (ADME, pharmacokinetics), using stable isotope labeled drugs to investigate drug metabolism in both in vitro and in vivo systems, metabolites are identified through high resolution LC-MS/MS profiling, both the original drug and their metabolites can be quantified in MRM mode with triple quadrupole mass spectrometer for pharmacokinetic and pharmacodynamic evaluation.

3. Disease biomarker discovery and validation (for diagnosis, therapeutic and pharmacodynamics study) using comparative metabolomic and proteomic approach.

4. Environmental analysis of both organic and inorganic pollutants (agrochemicals such as pesticide, herbicides, veterinary antimicrobials, animal growth hormones, their leakage into the environment; human medicine and brekdown products entering the eniviroment from waste water treatment plant) and environment originated antimicrobial resistance.

I teach year 2 Biochemistry student, Module LF219 (Tools for Biological Discovery) and various of master class for MIBTP students on Analytical Chemistry


I am supervising the following PhD students:

  • Lobna Hudifa, Bioactive natural product discovery using metagenomic approach (with Prof Liz Wellington)
  • Nazia Auckloo, High throughput approach for novel antibiotic discovery from bacterium (with Dr Chris Corre)
  • If you are interested in a PhD position, please contact me for more details.

Recent Publications (H-index 36), total citation>4,300:

  1. Borsetto, S. Raguideau, E. Travis, D. Kim, D. Lee, A. Bottrill, R. Stark, L. Song, J. Cha, J. Pearson, C. Quince, A. Singer, E. Wellington, Impact of sulfamethoxazole on a riverine microbiome, Water Research, 2021, in revision
  2. Zhou, H. Bhukya, N. Malet, P. Harrison, D. Rea, M. Belousoff, H. Venugopal, P. Sydor, K. Styles, L. Song, M. Cryle, L. Alkhalaf, V. Fulop, G. Challis, C. Corre, Structural basis for control of antibiotic production by bacterial hormones, Nature, 2021, 590, 463-467, Doi:10.1038/s41586-021-03195x
  3. Chhun, D. Sousoni, M. Aguilo-Ferretjans, L. Song, C. Corre, J. Christie-Oleza, Phytoplankton trigger the production of cryptic metabolites in the marine actinobacteria Salinispora tropica, Microbio. Biotech, 2020, 14 (1), 291-306, Doi:10.1111/1751-7915.13722
  4. Sidda, L. Song, J. Parker, D. Studholme, C. Sambles, M. Grant, Diversity of secoiridoid glycosides in leaves of UK and Danish ash provide new insight for ash dieback management, Scientific Rep., 2020, 10(1), 19566, DOI: 10.1038/541598-020-76140-z
  5. Zhou, N. Malet, L. Song, C. Corre, G. Challis, MmfL catalyses formation of a phosphorylated butenolide intermediate in methylenomycin furan biosynthesis, Chem Comm., 2020, 56(92), 14443-14446, DOI: 10.1039/D0CC05658H
  6. Zabala, L. Song, Y. Dashti, G. Challis, J. Salas, C, Mendez. Heterologous reconstitution of the biosynthesis pathway for 4-demethyl-premithramycinone, the aglycone of antitumor polyketide mithramycin, Microbial Cell Factory, 2020, 19 (1), 1-12
  7. Becher, V. Verschut, M. Bibb, M. Bush, B. Molnar, E. Barane, M. Bassam, G. Chandra, L. Song, G. Challis, M. Buttner, K. Flardh. Developmentally regulated volatiles geosmin and 2-methylisoborneol attract springtails to Streptomyces bacteria as vectors for spore dispersal, Nat. Microbiology, 2020, 5, 821-829
  8. Banks, L. Song, G. Challis, A. Bailey, G. Foster. Bovistol B, bovistol D and strossmayerin: Sesquiterpene metabolites from the culture filtrate of the basidiomycete Coprinopsis strossmayeri, PLoS ONE, 2020, 15(4):e0229925
  9. S. Zhou, L. Song, J. Masschelein, F. Sumang, I. Papa, T. Zulaybar, A. Custodio, D. Zabala, E. Alcantara, E. de los Santos, G. Challis. Pentamycin Biosynthesis in Philippine Streptomyces sp. S816: Cytochrome P450-Catalyzed Installation of the C‑14 Hydroxyl Group, ACS Chem. Biol., 2019, 14, 1305-1309 (DOI: 10.1021/acschembiol.9b00270)
  10. Thankachan, ;A. Fazal, D. Francis, L. Song, M. Webb, R. Seipke, A trans-​acting cyclase off-​loading strategy for non-​ribosomal peptide synthetases, ACS Chem Biol., 2019, 14, 845-849, (DOI:10.1021/acschembio.9b00095)
  11. Alberti, I. Wilkening, D. Leng, L. Song, C. Corre, A Pipeline for the Discovery of Natural Products from Genetically Intractable Bacteria, Chem Sci., 2019,10, 453-463
  12. Perry, J. Sargeant, L. Song, G. Challis, Relative stereochemical assignment of C33 and C35 in the antibiotic gladiolin, Tetrahedron, 2018, 74(38), 5150-5155
  13. Banerjee, J. Soldevila, J. Wolny, C. Wootton, Habtemariam, I. Romero, F. Chen, G. Clarkson, I. Prokes, L. Song, P. O'Connor, V. Schunemann, P. Sadler, New activation mechanism for half-sandwich organometallic anticancer complexes, Chem Sci., 2018, 9, 3177-3188
  14. Anderson, C. Hobson, R. Needley, L. Song, M. Perryman, P. Kerby, and D. Fox, NMR-based assignment of isoleucine vs allo-isoleucine stereochemistry. Organic & Biomolecular Chemistry 2017, 15, 9372-9378
  15. Blessborn, K. Kaewkhao, L. Song, NJ White, NPJ Day, J Tarning, Quantification of the antimalarial drug pyronaridine in whole blood using LC-MS/MS-increased sensitivity resulting from reduced non-specific binding, J Pharm Biomed Anal. 2017, 146: 214-219.
  16. L. Song, M. Jenner, J. Masschelein, C. Jone, S. Harris, C. Paisey, M. Bull, R. Haartknorn, S. Cole, P. Coupland, M. Dunn, R. Weiser, J. Parkhill, E. Mahenthiralingam, G. Challis, Discovery of gladiolin: a novel Burkholderia gladioli macrolide with potent antibiotic activity against Mycobacterium tuberculosis. J. Am. Chem. Soc. 2017, 139(23)7974-7981
  17. Tsypik, R. Makitrynskyy, A. Bera, L. Song, W. Wohlleben, V. Fedorenko, B. Ostash, Role of GntR Family Regulatory Gene SCO1678 in Gluconate Metabolism in Streptomyces coelicolor M145, BioMed Research International, 2017, pp 1-9, DOI.org/10.1155/2017/9529501
  18. Inahashi, S. Zhou, M. Bibb, L. Song, M. Al-Bassam, M. Bibb and G. Challis. Watasemycin biosynthesis in Streptomyces venezuelae: thiazoline C-methylation by a type B radical-SAM methylase homologue. Chem. Sci. 2017, 8 (4), 2823-2831
  19. Sotenko, S. Coles, G. Barker, L. Song, Y. Jiang, P. Longhurst, T. Romanova, O. Shuvaeva, K. Kirwan. Phytoremediation combined with biorefinery on the example of two agricultural crops grown on Ni soil and degraded by P. chrysosporium. Int. J. Phytoremediation., 2017 19(11), 965-975, DOI: 10.1080/15226514.2016.1267705
  20. Ray, T. Valentic, T. Miyazawa, D. Withall, L. Song, H. Osada, S. Takahashi, S. Tsai, G. Challis, Structural basis for acyl-CoA carboxylase-mediated assembly of unusual polyketide synthase extender units incorporated into the stambomycin antibiotics, Nat Comm., 2016, 7, 13609
  21. A. Thanapipatsiri, J. Gomez-Escribano, L. Song, M. Bibb, M. Al-Bassam, G. Chandra, A. Thamchaipenet, G. Challis and M. Bibb, Discovery of unusual biaryl polyketides by activation of a silent Streptomyces venezuelae biosynthetic gene cluster, ChemBioChem, 2016, 17, 2189-2198
  22. Zabala, J. Cartwright, D. Roberts, B. Law, L. Song, M. Samborskyy, P. Leadlay, J. Micklefield, and G. Challis. A flavin-dependent decarboxylase-dehydrogenase-monooxygenase assembles the warhead of α, β-epoxyketone proteasome inhibitors. J. Am. Chem. Soc. 2016, 137, 432-435
  23. Wilkening, S. Gazzola, E. Riva, J. Parascandolo, L. Song, M. Tosin. Second-generation probes for biosynthetic intermediate capture: towards a comprehensive profiling of polyketide assembly. Chem. Commun., 2016, 52, 10392-10395
  24. Sidda, V. Poon, L. Song, W. Wang, K. Yang, C. Corre. Overproduction and identification of butyrolactones SCB1-8 in the antibiotic production super host Streptomyces M1152. Org. Biomol. Chem., 2016, 14(27), 6390-6393
  25. Parascandolo, J. Havemann, H. Potter, F. Huang, E. Riva, J. Connolly, I. Wilkening, L. Song, P. Leadlay, M. Tosin, Novel insights into 6-methylsalicylic acid bio-assembly via chemical probes, Angew. Chem. Int. Ed. 2016, 55(10), 3463-3467
  26. Amaratunga, P. Lim, S. Suon, S. Sreng, S. Mao, C. Sopha, B. Sam, D. Dek, V. Try, R. Amato, D. Blessborn, L. Song, G. Tullo, M. Fay, J. Anderson, J. Tarning, R. Fairhurst. Dihydroartemisinin-piperaquine resistance in Plasmodium falciparum malaria in Cambodia: a multi-site observational cohort study, Lancet Infectious Disease, 2016, 16(3), 357-365
  27. Liu*, L. Song*, M. Liu*, F. Shang, Z. Anderson, D. Fox, G. L. Challis, Y. Huang, Unique post-translational ­oxime formation in the biosynthesis of the azolemycin complex of novel ribosomal peptides from Streptomyces sp. FXJ1.264, Chem. Sci., 2016, 7(1), 482-488 (* Co-first author)
  28. Uytterhoeven, K. Appermans, L. Song, J. Masschelein, C. Michiels, R. Lavigne, Systematic analysis of the kalimantacin assembly line NRPS module using an adapted targeted mutagenesis approach, Microbiology Open, 2016, 5(2), 279-286
  29. Leang, W. Taylor, D. Bouth, L. Song, J. Tarning, M. Char, S. Kim, B. Witkowski, V. Duru, A. Domergue, N. Khim, P. Ringwald, D. Menard, Evidence of falciparum malaria multidrug resistance to artemisinin and piperaquine in western Cambodia: dihydroartemisinin-piperaquine open-label multicenter clinical assessment. Antimicrob Agents Chemother. 2015, 59(8), 4719-4726
  30. Gubbens, H. Zhu, G. Girard, L. Song, B. Florea, P. Aston, K. Ichinose, D. Filippov, Y. Choi, H. Overkleeft, G. Challis, G. van Wezel, Natural Product Proteomining, a Quantitative proteomics platform, allows rapid discovery of biosynthetic gene clusters for different classes of natural products. Chem. Biol. 2014, 21(6), 707-718
  31. Song, L. Laureti, C. Corre, P. Leblond, B. Agile, G. L. Challis. Cytochrome P450-mediated hydroxylation is required for polyketide macrolactonisation in stambomycin biosynthesis. J. Antibiotic, 2014, 67, 71-76
  32. Sidda, L. Song, V. Poon, M. Al-Bassam, O. Lazos, M. Buttner, G. Challis, C. Corre. Discovery of a family of γ-aminobutyrate ureas via rational derepression of a silent bacterial gene cluster, Chem. Sci,, 2014, 5 (1), 86-89
  33. Suberu, P. Yamin, K. Leonhard, L. Song, S. Chemat, N. Sullivan, G. Barker, A. Lapkin . The effect of O-methylated flavonoids and other co-metabolites on the crystallization and purification of artemisinin. J. Biotechnol., 2014, 171, 25-33
  34. Suberu, L. Song, S. Slade, N. Sullivan, G. Barker, A. Lapkin, A rapid method for the determination of artemisinin and its biosynthetic precursor in Artemisia annua L. crude extract. J. Pharm. Biomed. Anal. 2013, 84, 269-277
  35. Kodani, J. Bicz, L. Song, R. Deeth, M. Ohnish-Kameyama,M. Yoshida, K. Ochi, and G. Challis. Structure and biosynthesis of scabichelin, a novel tris-hydroxamate siderophore produced by the plant pathogen Streptomyces scabies 87.22. Org. Biomol. Chem., 2013, 11, 4686-4694
  36. Zhao, J Woods, N. Farrer, K. Robinson, J. Pracharova, J. Kasparkova, O. Nokakova, H. Li, L. Salassa, A. Pizarro, G. Clarkson, L. Song, V. Brabec, P. Sadler, Diazido mixed-amine platinum(IV) anticancer complexes activatable by visible light form novel DNA adducts, Chem. Eur. J., 2013, 19(29), 9578-9591
  37. Gomez-Escribano*, L. Song*, M. Bibb, G. Challis, Posttranslational β-methylation and macrolactamidination in the biosynthesis of the bottromycin complex of ribosomal peptide antibiotics, Chem. Sci, 2012, 3, 3522-3525. (* co-first author)
  38. Barry, J. Kers, E. Johnson, L. Song, P. Aston, B. Patel, S. Krasnoff, B. Crane, D. Gibson, R. Loria and G. Challis. Cytochrome P450–catalyzed L-tryptophan nitration in thaxtomin phytotoxin biosynthesis. Nat. Chem. Biol. 2012, 8, 814-816.
  39. Gerc*, Song*, G. Challis, N. Stanley-Wall, S. Coulthurst, Identification and characterisation of the althiomycin biosynthetic operon of Serratia marcescens Db10, PLoS ONE, 2012, 7(9), e44673 (* Co-first Author).
  40. Gomez-Escribano*, L. Song*, D.Fox, M. Bibb, G. Challis, Identification of the yellow-pigmented polyketide product of the cryptic cpk gene cluster of Streptomyces coelicolor M145, Chem. Sci, 2012,3(9), 2716-2720. (* co-first author)
  41. Lautru, L. Song, L. Demange, H. Galons, G. L. Challis and Jean-Luc Pernodet. A Sweet Origin for the Key Congocidine Precursor 4-Acetamidopyrrole-2-carboxylate. Angew. Chem Int. Ed. 2012, 51(30), 7454-7458
  42. Fu, M. Romero, A. Habtemariam, M. Snowden, L. Song, G. Clarkson, B. Qamar, A. Pizarro, P. Unwin and P. Sadler, The Contrasting Chemical Reactivity of Potent Isoelectronic Iminopyridine and Azopyridine Osmium(II) Arene Anticancer Complexes, Chem. Sci, 2012, 3 (8), 2485 - 2494
  43. Milnes, M. McKee, J. Bath, L. Song , E. Stulz, A. Turberfield and R. O'Reilly, Sequence- specific synthesis of macromolecules using DNA-templated chemistry, Chem Comm, 2012, 48,5614-5616
  44. Song, L. Laureti, J.-P. Gomez-Escribano, D. Fox, V. Yeo, C. Corre, S. Huang, P. Leblond, B. Aigle, M. Bibb and G. L. Challis. Bacterial Genome Mining for Novel Natural Product Discovery. Planta Med. 2012, 78, 1030.
  45. Schmelz, C.H. Botting, L. Song, N. Kadi, G.L. Challis and J.H. Naismith. Structural basis for acyl acceptor specificity in the achrombactin biosynthetic enzyme AcsD. J. Mol. Biol. 2011, 412 (3)495-504
  46. Seipke, L. Song, J. Bic, P. Laskaris, A. Yaxley, G. L. Challis, R. Loria, Expression of a pyochelin biosynthetic gene cluster in Streptomyces scabies 87022 is regulated by TetR- and AfsR- family regulatory proteins. Microbiology. 2011, 157, 2681-2693
  47. Laureti*, L. Song*, S. Huang, C. Corre, P. Leblond, G.L. Challis and B. Aigle. A new class of bioactive macrolide discovered by activation of a silent polyketide synthase. Proc. Nat. Acad. Sci. USA. 2011,108(15), 6258-6263 , (*co-first author)
  48. Mahenthiralingam, L. Song, A. Sass, J. White, C. Wilmot, A. Marchbank, O. Boaisha, J. Paine, D. Knight, G. L. Challis, Enacyloxins are products of an unusual hybrid modular polyketide synthase encoded by a cryptic Burkholderia ambifaria genomic island. Chem. Biol. 2011, 18(5), 665-677
  49. Bunet, L. Song, M. V. Mendrea, C. Corre, L. Hotel, N. Rouhler, X. Framboisier, P Leblond, G. L. Challis, B. Aigle. Characterisation and manipulation of the pathway specific regulator AlpW reveals Streptomyces ambofaciens a new producer of kinamycins. J. Bacteriol. 2011, 195, 1142-1153
  50. Sydor, S. Barry, O. Odulate, F. Barona-Gomez, S. Haynes, C. Corre, L. Song, G.L. Challis, Antibiotic Oxidative Carbocyclizations Catalyzed by Rieske Oxygenase-Like Enzymes, Nat. Chem., 2011, 3, 388-392
  51. Haynes, P. Sydor, C. Corre, L. Song, and G.L. Challis. Stereochemical elucidation of streptorubin B. J. Am. Chem. Soc. 2011, 133 (6), 1793-1798
  52. Aigle, R. Bunet, C. Corre,; A. Garenaux, L. Hotel, S. Huang, L. Laureti, S. Lautru, M. Mendes, S. Nezbedova, H. Nguyen, L. Song, J. Weiser, G. Challis, P. Leblond, J.Pernodet.  Genome-guided exploration of Streptomyces ambofaciens secondary metabolism. Streptomyces, 2011, 179-194.
  53. Patel, L Song, G.L.Challis, Distinct extracytoplasmic siderophore binding proteins recognise ferrioxamines and ferricoelichelin in Streptomyces Coelicolor A3(2), Biochemistry, 2010, 49, 8033-8042
  54. Chen, J. Scanlan, L Song, A. Crombie, M. Rahman, H. Schafer, C. Murrell, γ-glutamylmethylamide is essential in the metabolism of methylamine by Methylocella silvestris BL2. Appl. Environ Microbiol. 2010, 76(3), 4530-4537
  55. Corre, S. Haynes, N. Malet, L. Song and G. Challis, A butenolide intermediate in methylenomycin furan biosynthesis is implied by incorporation of stereospecifically 13C-labelled glycerols, Chem. Commun. 2010, 46, 4079-4081
  56. Oves-Costales, L. Song and G.L. Challis. Enantioselective desymmetrisation of citric acid catalysed by the substrate-tolerant petrobactin biosynthetic enzyme AsbA. Chem. Commun. 2009, 1389-1391.
  57. Schmelz, N. Kadi, S. McMahon, L. Song, D. Oves-Costales, M. Oke, H. Liu, K. Johnson, L.G. Carter, C.H. Botting, M.F. White, G.L. Challis and J.H. Naismith, AcsD catalyzes enantioselective citrate desymmetrization in siderophore biosynthesis. Nat. Chem. Biol. 2009, 5, 174-182.
  58. Corre, L. Song, S. O'Rourke, K. F. Chater and G. L. Challis. 2-Alkyl-4-hydroxymethylfuran-3-carboxylic acids, antibiotic production inducers discovered by Streptomyces coelicolor genome mining. Proc. Natl. Acad. Sci. USA 2008, 105, 17510-17515.
  59. Kadi, L. Song and G. L. Challis. Bisucaberin biosynthesis: An adenylating domain of the BibC multi-enzyme catalyzes cyclodimerization of N-hydroxy-N-succinylcadaverine. Chem. Commun. 2008, 5119-5121.
  60. Mitchell, M.T.G. Holden, J. Parkhill, L. Song, G.L. Challis, C. Robinson, N. Davis-Poynter and A.S. Waller. A novel streptococcal integrative conjugative element involved in iron acquisition. Mol. Microbiol. 2008, 70, 1274-1292.
  61. Oves-Costales, N. Kadi, M.J. Fogg, L. Song, K.S. Wilson and G.L. Challis. Petrobactin biosynthesis: AsbB catalyses ATP-dependent condensation of spermidine with N8-citryl-spermidine and its N1-(3, 4-dihydroxybenzyl) derivative. Chem. Commun. 2008, 4034-4036.
  62. Kadi, S. Arbache, L. Song, D. Oves-Costales and G.L. Challis. Identification of a gene cluster that directs putrebactin biosynthesis in Shewanella species: PubC catalyzes ATP-dependent cyclodimerization of N-hydroxy-N-succinyl-putrescine. J. Am. Chem. Soc. 2008, 130, 10458-10459.
  63. Haynes, P. Sydor, A. Stanley, L. Song and G.L. Challis. Role and substrate specificity of the Streptomyces coelicolor RedH enzyme in undecylprodiginine biosynthesis. Chem. Commun. 2008, 1865-1867.
  64. Mo, P. Sydor, C. Corre, M. Alhamadsheh, A. Stanley, S. Haynes, L. Song, K.A. Reynolds and G.L. Challis. Elucidation of the Streptomyces coelicolor pathway to 2-undecylpyrrole, a key intermediate in undecylprodiginine and streptorubin B biosynthesis. Chem. Biol. 2008, 15, 137-148.
  65. Oves-Costales, N. Kadi, M. Fogg, L. Song, K. Wilson, G.L. Challis, Enzymatic logic of anthrax stealth siderophore biosynthesis: AsbA catalyzes ATP-dependant condensation of citric acid and spermidine, J. Am. Chem. Soc., 2007, 129, 6017-6018
  66. Song and P. Thornalley, Effects of storage, cooking and processing on glucosinolates and related metabolites in Brassica vegetables, Food and Chem. Toxicl., 2007, 45, 216-224
  67. Song, F. Barona-Gomez, C. Corre, L. Xiang, D. W. Udwary, M. Austin, J. P. Noel, B. S. Moore and G. L. Challis, Type III polyketide synthase extender unit specificity in germicidin biosynthesis discovered by Streptomyces coelicolor genome mining, J. Am. Chem. Soc., 2006, 128, 14754-14755
  68. Dobler, N. Ahmad, L. Song, K. Eboigbodin, P. Thornalley, Increased dicarbonyl metabolism in endothelial cells in hyperglycemia induces anoikis and impairs angiogenesis by RGD and GFOGER motif modification, Diabetes, 2006, 55, 1961-1969
  69. Song, R. Iori, P. Thornalley, Purification of major glucosinolates from Brassicaceae seeds and preparation of isothiocyanates and amine metabolites, J. Sci. Food and Agriculture.  2006, 86, 1271-1280
  70. Song, J. Morrison, N. Botting, P. Thornalley, Analysis of glucosinolates, isothiocyanates and amines degradation products in vegetable extracts and blood plasma by LC-MS/MS, Analytical Biochemistry, 2005, 347, 234-243
  71. McWalter, L. Higgins, L, McLellan, C. Henderson, L. Song, P. Thornalley, K. Itoh, M. Yamamoto, J. Hayes. Transcription factor Nrf2 is essential for induction of NAD(P)H:quinone oxidoreductase 1, glutathione S-transferase, and glutathione cysteine ligase by broccoli seeds and isothiocyanates, J. Nutrition, 2004, 134, 3499s-3506s