个人简介

B.Sc. (Hons), The Univeristy of Leeds, UK Ph.D., The University of British Columbia Postdoctoral Research, The Scripps Institution of Oceanography at UCSD, and The Smithsonian Tropical Research Institute, Panama

研究领域

Natural Products Chemistry

Natural Products Chemistry metabolomics, high content screen design and development, drug discovery, chemical biology The Linington lab is focused upon contemporary applications of marine natural products chemistry to biological problems. Within this general area we have specific interests in the development of new high-content screening technologies, the discovery and hit-to-lead development of lead scaffolds for drug development, and the determination of compound modes of action. The overall objectives of this research platform are the discovery of new compound classes for drug development against pathogenic bacteria, cancer, and global health parasites, and the creation of chemical probes to explore the basic biology of these target organisms. To accomplish these objectives, the research program employs techniques spanning an array of disciplines including marine microbiology, natural products isolation and structure elucidation, bioassay design and development, synthetic medicinal chemistry, and 'omics' approaches to problems in biomedical research, including the development of new metabolomics tools for chemical and biological characterization of complex natural product libraries. This combination of techniques provides a mechanism for the examination of complex problems at the interface of chemistry and biology, using modern methods and analytical technologies to explore how natural products can contribute to our understanding of disease and disease treatment.

近期论文

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Tran, A. T.; Watson, E. E.; Pujari, V.; Conroy, T.; Dowman, L. J.; Giltrap, A. M.; Pang, A.; Wong, W.-R.; Linington, R. G.; Mahapatra, S.; Saunders, J.; Charman, S. A.; West, N. P.; Bugg, T. D. H.; Tod, J.; Dowson, C. G.; Roper, D. I.; Crick, D. C.; Britton, W. J.; Payne, R. J..* "Sansanmycin natural product analogues as potent and selective anti-mycobacterials that inhibit lipid I biosynthesis" Nature Communications, 2017, 8, Article number: 14414 59. Morgan, J. M.; Duncan, M. C.; Johnson, K. S.; Diepold, A.; Lam, H.; Dupzyk, A. J.; Martin, L. R.; Wong, W.-R.; Armitage, J. P.; Linington, R. G.; Auerbuch, V.* "Piericidin A1 blocks Yersinia Ysc type III secretion system needle assembly" mSphere, 2017, 2:e00030-17. 2016 58. Harms, H.; Kurita, K. L.; Pan, L.; Wahome, P. G.; He, H.; Kinghorn, A. D.; Carter, G. T.; Linington, R. G.* "Discovery of Anabaenopeptin 679 From Freshwater Algal Bloom Material: Insights Into the Structure-Activity Relationship of Anabaenopeptin Protease Inhibitors" Bioorganic and Medicinal Chemistry Letters, 2016, 26, 4960-4965. 57. Wang, M.; Carver, J. J.; Phelan, V. V.; Sanchez, L. M.; Garg, N. et al (113 others) "Sharing and Community Curation of Mass Spectrometry Data with Global Natural Products Social Molecular Networking" Nature Biotechnology, 2016, 34, 828-837. 56. Giltrap, A. M.; Dowman, L. J.; Nagalingam, G.; Ochoa, J. L.; Linington, R. G.; Britton, W. J.; Payne, R. J.* "Total Synthesis of Teixobactin." Organic Letters, 2016, 18, 2788–2791. 55. Sanchez, L. M.; Cheng, A. T.; Warner, C. J. A.; Townsley, L.; Peach, K. C.; Navarro, G.; Shikuma, N. J.; Bray, W. M.; Riener, R. M.; Yildiz, F. H.; Linington, R. G.* "Biofilm Formation and Detachment in Gram-Negative Pathogens Is Modulated by Select Bile Acids." PLOS ONE, 2016, 11, e0149603. 2015 54. Effenberger, K. A.‡; James, R. C..‡; Urabe, V. K.; Dickey, B. J.; Linington, R. G.*, Jurica, M. S.* "The Natural Product N-palmitoyl-L-leucine Selectively Inhibits Late Assembly of Human Spliceosomes." Journal of Biological Chemistry, 2015, 290, 27524 - 27531. PMID: 26408199 53. Kurita, K. L.; Glassey, E.; Linington, R. G.* "Integration of High-Content Screening and Untargeted Metabolomics for Comprehensive Functional Annotation of Natural Product Libraries." Proceedings of the National Academy of Sciences, USA, 2015, 112, 11999-12004. PMID: 26371303 52. Ochoa, J. L.; Bray, W. M.; Lokey, R. S.; Linington, R. G.* "Phenotype-Guided Natural Products Discovery Using Cytological Profiling." Journal of Natural Products, 2015, 78, 2242-2248. PMID: 26292657 51. Schulze, C. J.; Donia, M. S.; Siqueira-Neto, J. L.; Ray, D.; Raskatov, J. A.; Green, R. E.; McKerrow, J. H.; Fischbach, M. A.; Linington, R. G.* "Genome-Directed Lead Discovery: Biosynthesis, Structure Elucidation, and Biological Evaluation of Two Families of Polyene Macrolactams against Trypanosoma brucei." ACS Chemical Biology, 2015, 16, 2373 - 2381. PMID: 26270237 50. Shao, C. L.; Linington, R. G.; Balunas, M. J.; Centeno, A.; Boudreau, P.; Zhang, C.; Engene, N.; Spadafora, C.; Mutka, T. S.; Kyle, D. E.; Gerwick, L.; Wang, C. Y.; Gerwick, W. H.* “Bastimolide A, a Potent Antimalarial Polyhydroxy Macrolide from the Marine Cyanobacterium Okeania hirsuta.” Journal of Organic Chemistry, 2015, 80, 6849-7855. PMID: 26222145 49. León, B.; Haeckl, F. J.; Linington, R. G.* “Optimized Quinoline Amino Alcohols as Disruptors and Dispersal Agents of Vibrio cholerae Biofilms.” Organic and Biomolecular Chemistry, 2015, 13, 8495 - 8499. PMID: 26156292 48. Teschler, J. K.; Zamorano-Sánchez, D.; Utada, A. S.; Warner, C. J. A.; Wong, G. C. L.; Linington, R. G.; Yildiz F. H.* “Living in the Matrix: Assembly and Control of Vibrio cholerae biofilms” Nature Reviews Microbiology, 2015, 13, 255 - 268. PMID: 25895940 47. Kurita, K. L.; Linington, R. G.* “Connecting Phenotype and Chemotype: High-Content Discovery Strategies for Natural Products Research” Journal of Natural Products, 2015, 78, 587 - 596. PMID: 25728167 46. Schulze, C. J.‡; Navarro, G.‡; Ebert, D.‡; DeRisi, J.*; Linington, R. G.* “Salinipostins A−K, Long-Chain Bicyclic Phosphotriesters as a Potent and Selective Antimalarial Chemotype” Journal of Organic Chemistry, 2015, 80, 1312-1320. PMID: 25584395 45. León, B.‡; Navarro, G.‡; Dickey, B. J.; Stepan, G.; Tsai, A.; Jones, G. S.; Morales, M. E.; Barnes, T.; Ahmadyar, S.; Tsiang, M.; Geleziunas, R.; Cihlar, T.; Pagratis, N.; Tian, Y.; Yu, H.; Linington, R. G.* “Abyssomicin 2 Reactivates Latent HIV‐1 by a PKC- and HDAC- Independent Mechanism” Organic Letters, 2015, 15, 262-265. PMID: 25560385 44. Warner, C. J. A; Cheng, A. T.; Yildiz, F. H.; Linington, R. G.* “Development of Benzo[1,4]oxazines as Biofilm Inhibitors and Dispersal Agents Against Vibrio cholerae” ChemComm, 2015, 51, 1305-1308. PMCID: PMC4288701 2014 43. Schulze, C. J.; Bray, W. M.; Loganzo, F.; Lam, M.-H.; Szal, T.; Villalobos, A.; Koehn, F.; Linington, R. G.* “Borrelidin B: Isolation, Biological Activity, and Implications for Nitrile Biosynthesis” J. Nat. Prod., 2014, 77, 2570-2574. PMID: 25393949 42. Donia, M.; Cimermancic, P.; Schulze, C. J.; Wieland Brown, L. C.; Martin, J.; Makedonka, M.; Clardy, J.; Linington, R. G.; Fischbach, M. A.* “A Systematic Analysis of Biosynthetic Gene Clusters in the Human Microbiome Reveals a Common Family of Antibiotics” Cell, 2014, 158, 1402-1414. PMCID: PMC4164201 41. Cimermancic, P.; Medema, M. H.; Claesen, J.; Kurita, K.; Wieland Brown, L. C.; Mavrommatis, K.; Pati, A.; Godfrey, P. A.; Koehrsen, M.; Clardy, J.; Birren, B. W.; Takano, E.; Sali, A.; Linington, R. G.; Fischbach, M. A.* “Insights into Secondary Metabolism from a Global Analysis of Prokaryotic Biosynthetic Gene Clusters” Cell, 2014, 158, 412-421. PMCID: PMC4123684