Relevant Publications

Genome-Wide Screening for Target ID and Validation:

  • Teo, H.; Ghosh, S.; Luesch, H.; Ghosh, A.; Wong, E. T.; Malik, N.; Orth, A.; de Jesus, P.; Perry, A. S.; Oliver, J. D.; Tran, N. L.; Speiser, L. J.; Wong, M.; Saez, E.; Schultz, P.; Chanda, S. K.; Verma, I. M.; Tergaonkar, V. “Telomere-independent Rap1 is an IKK adaptor and regulates NF-κB-dependent gene expression” Nature Cell Biol. 2010, 12, 758–767.
  • Luesch, H.; Abreu, P. “A natural products approach to drug discovery: probing modes of action of antitumor agents by genome-scale cDNA library screening” Methods Mol. Biol. 2009, 572, 261–277.
  • Luesch, H.; Liu, Y. “Genome-wide overexpression screen for activators of antioxidant gene transcription” Methods Mol. Biol. 2008, 477, 343–354.
  • Liu, Y.; Kern, J. T.; Walker, J. R.; Johnson, J. A.; Schultz, P. G.; Luesch, H. “A Genomic Screen for Activators of the Antioxidant Response Element” Proc. Natl. Acad. Sci. USA 2007, 104, 5205–5210.
  • Luesch, H.; Chanda, S. K.; Raya, R. M.; DeJesus, P. D.; Orth, A. P.; Walker, J. R.; Izpisúa Belmonte, J. C.; Schultz, P. G. “A Functional Genomics Approach to the Mode of Action of Apratoxin A” Nature Chem. Biol. 2006, 2, 158–167.
  •  Luesch, H.; Wu, T. Y. H.; Ren, P.; Gray, N. S.; Schultz, P. G.; Supek, F. “A Genome-Wide Overexpression Screen in Yeast for Small-Molecule Target Identification” Chem. Biol. 2005, 12, 55–63.

Small Molecule, Peptoid and Natural Products-like Library HTS in Cells or Whole Organisms:

  • Wang, R.; Mason, D. E.; Choe, K. P.; Lewin, A. S.; Peters, E. C.; Luesch, H. “In Vitro and in Vivo Characterization of a Tunable Dual-Reactivity Probe of the Nrf2-ARE Pathway” ACS Chem. Biol. 2013, 8, 1764‒1774.
  • Leung, C. K.; Wang, Y.; Malany, S.; Deonarine, A.; Nguyen, K.; Vasile, S.; Choe, K. P. “An ultra high-throughput, whole-animal screen for small molecule modulators of a specific genetic pathway in Caenorhabditis elegans” PLoS One 2013, 8, e62166.
  • Huigens III, R. W.; Morrison, K. C.; Hicklin, R. W.; Flood Jr., T. A.; Richter, M. F.; Hergenrother, P. J. “A ring-distortion strategy to construct stereochemically complex and structurally diverse compounds from natural products.” Nature Chem. 2013, 5, 195‒202.
  • Leung, C. K.; Deonarine, A.; Strange, K.; Choe, K. P. “High-Throughput screening and biosensing with fluorescent C. elegans strains” J. Vis. Exp. 2011, e2745.
  • Hur, W.; Sun, Z.; Jiang, T.; Mason, D. E.; Peters, E. C.; Zhang, D. D.; Luesch, H.; Schultz, P. G.; Gray, N. S. “A Small-Molecule Inducer of the Antioxidant Response Element” Chem. Biol. 2010, 17, 537–547.

Natural Products-Inspired Drug Discovery and Development:

  • Salvador, L. A.; Taori, K.; Biggs, J. S.; Jakoncic, J.; Ostrov, D. A.; Paul, V. J.; Luesch, H. “Potent Elastase Inhibitors from Cyanobacteria: Structural Basis and Mechanisms Mediating Cytoprotective and Anti-Inflammatory Effects in Bronchial Epithelial Cells” J. Med. Chem. 2013, 56, 1276‒1290.
  • Law, M. E.; Corsino, P. E.; Jahn, S. C.; Davis, B. J.; Chen, S.; Patel, B.; Pham, K.; Lu, J.; Sheppard, B.; Nørgaard, P.; Hong, J.; Higgins, P.; Kim, J.-S.; Luesch, H.; Law, B. K. “Glucocorticoids and histone deacetylase inhibitors cooperate to block the invasiveness of basal-like breast cancer cells through novel mechanisms” Oncogene 2013, 32, 1316‒1329.
  • Liu, Y.; Zhang, W.; Li, L.; Salvador, L. A.; Chen, T.; Chen, W.; Felsenstein, K. M.; Ladd, T. B.; Price, A. R.; Golde, T. E.; He, J.; Xu, Y.; Li, Y.; Luesch, H. “Cyanobacterial Peptides as a Prototype for the Design of Potent β-Secretase Inhibitors and the Development of Selective Chemical Probes for Other Aspartic Proteases” J. Med. Chem. 2012, 55, 10749‒10765.
  • Hong, J.; Luesch, H. “Largazole: From Discovery to Broad-Spectrum Therapy” Nat. Prod. Rep. 2012, 29, 449‒456.
  • Chen, Q.-Y.; Liu, Y.; Luesch, H. “Systematic Chemical Mutagenesis Identifies a Potent Novel Apratoxin A/E Hybrid with Improved in Vivo Antitumor Activity” ACS Med. Chem. Lett. 2011, 2, 861‒865.
  • Liu, Y.; Salvador, L. A.; Byeon, S.; Ying, Y.; Kwan, J. C.; Law, B. K.; Hong, J.; Luesch, H. “Anticolon Cancer Activity of Largazole, a Marine-Derived Tunable Histone Deacetylase Inhibitor” J. Pharmacol. Exp. Ther. 2010, 335, 351–361.
  • Huigens III, R. W.; Reyes, S.; Reed, C. S.; Bunders, C.; Rogers, S. A.; Steinhauer, A. T.; Melander, C. “The chemical synthesis and antibiotic activity of a diverse library of 2-aminobenzimidazole small molecules against MRSA and multidrug-resistant A. baumanniiBioorg. Med. Chem. 2010, 18, 663‒674.
  • Taori, K.; Liu, Y.; Paul, V. J.; Luesch, H. “Combinatorial Strategies by Marine Cyanobacteria: Symplostatin 4, an Antimitotic Natural Dolastatin 10/15 Hybrid that Synergizes with the Coproduced HDAC Inhibitor Largazole” ChemBioChem 2009, 10, 1634–1639.
  • Ying, Y.; Taori, K.; Kim, H.; Hong, J.; Luesch, H. “Total Synthesis and Molecular Target of Largazole, a Histone Deacetylase Inhibitor” J. Am. Chem. Soc. 2008, 130, 8455–8459.
  • Taori, K.; Paul, V. J.; Luesch, H. “Structure and Activity of Largazole, a Potent Antiproliferative Agent from the Floridian Marine Cyanobacterium Symploca sp.”  J. Am. Chem. Soc. 2008, 130, 1806–1807.
  • Huigens III, R. W.; Ma, L.; Gambino, C.; Moeller, P. D. R.; Basso, A.; Cavanagh, J.; Wozniack, D. J.; Melander, C. “Control of bacterial biofilms with marine alkaloid derivatives” Mol. BioSys. 2008, 4, 614‒621.
  • Huigens III, R. W.; Richards J. J.; Parise, G.; Ballard, T. E.; Zeng, W.; Deora, R.; Melander, C. “Inhibition of Pseudomonas aeruginosa biofilm formation with bromoageliferin analogues” J. Am. Chem. Soc. 2007, 129, 6966‒6967.

Microbial Genomics and Biosynthesis:

  • Dimise, E. J.; Condurso, H. L.; Stoker, G. E.; Bruner, S. D. “Synthesis and structure confirmation of fuscachelins A and B, structurally unique natural product siderophores from Thermobifida fuscaOrg. Biomol. Chem. 2012, 5353‒5356.
  • Liu, Y.; Zheng, T.; Bruner, S. “Structural basis for phosphopantetheinyl carrier domain interactions in the terminal module of nonribosomal peptide synthetases” Chem. Biol. 2011, 18, 1482‒1488.
  • Ding, Y.; Rath, C. M.; Bolduc, K. L., Håkansson, K.; Sherman, D. H. “Chemoenzymatic synthesis of cryptophycin anticancer agents by an ester bond-forming non-ribosomal peptide synthetase module” J. Am. Chem. Soc. 2011, 133, 14492‒14495.
  • Ding, Y.; Wet, J. R.; Cavalcoli, J.; Li, S.; Greshock, T. J.; Miller, K. A.; Finefield, J. M.; Sunderhaus, J. D.; McAfoos, T. J.; Tsukamoto, S.; Williams, R. M.; Sherman, D. H. “Genome-based characterization of two prenylation steps in the assembly of the stephacidin and notoamide anticancer agents in a marine Aspergillus sp.” J. Am. Chem. Soc. 2010, 132, 12733‒12740.
  • Ding, Y.; Williams, R. M.; Sherman, D. H. “Isolation and characterization of a 4-dimethylallyltryptophan synthase from Malbranchea aurantiacaJ. Biol. Chem. 2008, 283, 16068‒16076.
  • Ding, Y.; Seufert, W. H.; Beck, Z. Q.; Sherman, D. H. “Analysis of the cryptophycin P450 epoxidase reveals substrate tolerance and cooperativity” J. Am. Chem. Soc. 2008, 130, 5492‒5498.
  • Dimise, E. J.; Widboom, P. F.; Bruner, S. D. “Structure elucidation and biosynthesis of fuscachelins, peptide siderophores from the moderate thermophile Thermobifida fuscaProc. Natl. Acad. Sci. USA 2008, 105, 15311‒15316.
  • Widboom, P. F.; Fielding, E. N.; Liu , Y.; Bruner, S. D. “Structural basis for cofactor-independent dioxygenation in vancomycin biosynthesis” Nature 2007, 447, 342-345.
  • Magarvey, N. A.; Beck, Z. Q.; Golakoti, T.; Ding, Y.; Huber, U.; Hemscheidt, T. K.; Abelson, D.; Moore, R. E.; Sherman, D. H. “Biosynthetic characterization and chemoenzymatic assembly of the cryptophycins. Potent anticancer agents from cyanobionts” ACS Chem. Biol. 2006, 1, 766‒779.
  • Luesch, H.; Hoffmann, D.; Hevel, J. M.; Becker, J. E.; Golakoti, T.; Moore, R. E. “Biosynthesis of 4-Methylproline in Cyanobacteria: Cloning of nosE and nosF Genes and Biochemical Characterization of the Encoded Dehydrogenase and Reductase Activities” J. Org. Chem. 2003, 68, 83–91.

Dietary Natural Products:

  • Ratnayake, R.; Liu, Y.; Paul, V. J.; Luesch, H. “Cultivated Sea Lettuce is a Multiorgan Protector from Oxidative and Inflammatory Stress by Enhancing the Endogenous Antioxidant Defense System” Cancer Prev. Res. 2013, 6, 989‒999.
  • Wang, R.; Paul, V. J.; Luesch, H. “Seaweed extracts and unsaturated fatty acid constituents from the green alga Ulva lactuca as activators of the cytoprotective Nrf2‒ARE pathway” Free Radic. Biol. Med. 2013, 57, 141‒153.