Presentations

  • McPhail, K.L. “Microbial Macrocycles that Disrupt Protein Synthesis and Function.” Gordon Research Conference on Marine Natural Products, Ventura, California. Invited speaker. Presentation, Presented, 03/14/2024.
  • McPhail, K.L. “Microbial Macrocycles that Inhibit Protein Synthesis and Secretion.” College of Pharmacy. University of Utah, Salt Lake City. Presentation, Presented, 11/02/2023.
  • McPhail, K.L. “Untargeted metabolomics to characterize microbial communities and guide natural products discovery.” OSU Department of Botany and Plant Pathology. Presentation, Presented, 02/09/2023.
  • McPhail, K.L. “Structure and Function of Microbial Natural Product Macrocycles.” School of Chemistry and Biochemistry. Georgia Tech, Atlanta. Presentation, Presented, 02/01/2023.
  • McPhail, K.L. “Structure and Function of Microbial Natural Product Macrocycles.” South African Chemical Institute (SACI-44), Cape Town, South Africa. Invited speaker. Presentation, Presented, 01/13/2023.
  • McPhail, KL. “Microbial communities in South African peritidal tufa stromatolites.” Pacifichem. Virtual platform/Honolulu. Invited speaker. Presentation, Presented, 12/19/2021.
  • McPhail, KL. “Translating Nature's Chemical Repertoire: Opportunities for Chemists and Chemical Engineers. ACS Presidential Symposium, Fall 2022. Virtual Platform. Invited speaker. Presentation, Presented, 08/23/2021.
  • McPhail, KL. “Microbial natural products as inhibitors of protein secretion.” ACS NORM 2021. Virtual Platform. Invited speaker. Presentation, Presented, 05/10/2021.
  • McPhail, K.L. “Molecular Networking and Integrated Tools for Multi-omics Natural Products Discovery.” OSU Pharmaceutical Sciences Departmental Seminar Series. Zoom. Presentation, Presented, 11/05/2020.
  • McPhail, KL. “GNPS Molecular Networking Tools Guide Biological Activity Hypotheses for Complex Extracts.” GNPS First Users Meeting. Virtual by Zoom. Keynote speaker. Invited Talk/Keynote, Presented, 08/26/2020.

Grants, Contracts & Research Gifts

  • Modulation of Protein Biogenesis and Secretion by Natural Product Translocon Ligands. PI: McPhail. Co-PI(s): Ishmael. NIH/NIGMS, 09/01/2023 - 08/31/2027. Total project budget to date: $1,643,712.00

Research Description

Uncommon organisms adapted to specific habitats and at habitat interfaces are rational sources of specialized metabolites with important biological properties related to the ecology and evolution of these organisms. The McPhail Lab is interested in characterizing macrocyclic natural products, for example, from insect-associated fungi, cyanobacteria, sea squirts and salamander microbiomes, that may serve as biomedical research tools or starting points for new disease treatments.

We use two distinct approaches for natural products chemistry:

  1. Chromatographic isolation and structure elucidation of new natural products, using NMR spectroscopy, mass spectrometry, and chemical degradation/derivatization, and guided by biological activity testing.
  2. Untargeted metabolomics using LCMS/MS for comparative computational analyses of limited environmental samples, and integration with genomic sequence data.

Our specific projects include working with an internationally collaborative group to characterize microbial macrocycles, such as coibamide A, that inhibit the Sec61 translocon or regulate protein translation by interacting with the ribosomal nascent complex as molecular glues. As much as 40% of the human proteome are secreted or membrane proteins that are synthesized at the endoplasmic reticulum (ER), and potentially dysregulated in chronic diseases. Organisms such as cyanobacteria, fungi and human pathogenic bacteria produce inhibitors of the Sec61 protein translocon complex, which translocates a majority of secreted and membrane proteins across the ER membrane during their initial biogenesis.

A second nationally collaborative project (https://herptilemicrobiomes.org/) investigates the herptile gut microbiome with the aim of demonstrating that the animal gut promotes horizontal gene transfer (HGT) between bacteria and fungi, and that this HGT selects for specific metabolites that function in microbial interactions in native microbiome.

Publications

  • Avalon, N.E.,* Reis, M.A.,* Thornburg, C.C.,* Williamson, R.T., Petras, D, Aron, A.T…McPhail, K.L., Gerwick, W.H. et al. Leptochelins A-C, Cytotoxic Metallophores Produced by Geographically Dispersed Leptothoe Strains of Marine Cyanobacteria. J. Am. Chem. Soc. 2024, 146, 27: 18626–18638. Published, 01/2024.
  • Neuhaus, G.F., Aron, A.T., Isemonger, E.W., Petras, D., Waterworth, S.C., Madonsela, L.S., Gentry, E.C., Siwe Noundou, X., Kalinski, J-C.J., Polyzois, A., Habiyaremye, J.C., Redick, M.A., Kwan, J.C., Dorrington, R.A., Dorrestein, P.C., McPhail, K.L. Environmental metabolomics characterization of modern stromatolites and annotation of ibhayipeptolides. PLoS ONE 2024, 19(5): e0303273. https://doi.org/10.1371/journal.pone.0303273. Published, 01/2024.
  • Mattos, D.R., das Neves, W., Kitamura, T., Pradhan, R., Wan, X., da Hora, C.C., Tranter, D., Kazemi, S., Yu, X., Tripathy, N., Paavilainen, V.O., McPhail, K.L., Oishi, S., Badr, C.E., Ishmael, J.E. Diastereomers of Coibamide A show altered Sec61 Client Selectivity and Ligand-Dependent Activity against Patient-derived Glioma Stem-Like Cells. ACS. Pharmacol. Translation. Sci. 2024, 7(6): 1823–1838. Published, 01/2024.
  • Zuffa, S., Schmid, R., Bauermeister, A., Dorrestein, P.C. et al. microbeMASST: a taxonomically informed mass spectrometry search tool for microbial metabolomics data. Nat. Microbiol. 2024, 9: 336–345. https://doi.org/10.1038/s41564-023-01575-9. Published, 12/2024.
  • Vargas-Gastélum, L., Romer, A.S., Alexander, N.R., Ghotbi, M., Dallas, J.W., Alexander, N.R., Moe, K.C., McPhail, K.L., Neuhaus, G.F., Shadmani, L., Spatafora, J.W., Stajich, J.E., Tabima, J.F., Walker, D.M. Herptile gut microbiomes: a natural system to study multi-kingdom interactions between filamentous fungi and bacteria. mSphere, 2024. 9:e00475-23. Doi: 10.1128/msphere.00475-23. Published, 01/2024.
  • Redick, M.A., Cummings, M.E., Neuhaus, G.F., Ardor Belluci, L.M., Thurber, A.R., McPhail, K.L. Integration of Untargeted Metabolomics and Microbial Community Analyses to Characterize Distinct Deep-Sea Methane Seeps. Frontiers in Marine Science, 2023, 10: 1197338. Doi: 10.3389/fmars.2023.1197338. Published, 01/2023.
  • Cummings, M.E., Ardor Bellucci, L.M., Seabrook, S., Raineault, N.A., McPhail, K.L., Thurber A.R. Variations and gradients between methane seep and off-seep microbial communities in a submarine canyon system in the Northeast Pacific. PeerJ, 2023,11: e15119. Published, 12/2023.
  • Davies-Coleman, M.T., McPhail, K.L., Parker-Nance, S. A Quarter Century of Marine Biodiscovery in Algoa Bay, South Africa. J. Nat. Prod. 2023, 86: 638–652. Published, 12/2023.
  • Suzuki, R., Mattos, D.R., Kitamura, T., Tsujioka, R., Kobayashi, K., Inuki, S., Ohno, H., Ishmael, J.E., McPhail, K.L., Oishi, S. Design of Synthetic Surrogates for the Macrolactone Linker Motif in Coibamide A. ACS Med. Chem. Lett. 2023, 14:1344–1350. Published, 12/2023.
  • Tehan, R.M., Dooley, C.B., Barge, E.G., McPhail, K.L., Spatafora, J.W. New species and new combinations in the genus Paraisaria (Hypocreales, Ophiocordycipitaceae) from the U.S.A., supported by polyphasic analysis. Mycokeys 2023, 100: 69-94. Published, 12/2023.
  • Andrianasolo, E.H., Haramaty, L., McPhail, K.L., Lutz, R.A. Bathymodiolamides C, D, and E, Necrosis Inducers from a Deep-Sea Hydrothermal Vent Invertebrate Mussel, Bathymodiolus azoricus. Journal of Shellfish Research 2023, 42: 177-197. Published, 12/2023.
  • Tehan, R.M.; Blount, R.R.; Goold, R.L.; Mattos, D.R.; Spatafora, N.R.; Tabima, J.F.; Gazis, R.; Wang, C.; Ishmael, J.E.; Spatafora, J.W.; McPhail, K.L. Tolypocladamide H and the Proposed Tolypocladamide NRPS in Tolypocladium Species. Journal of Natural Products. 2022, 85: 1363-1373. Published, 12/2022.
  • Kitamura, T.; Suzuki, R.; Inuki, S.; Ohno, H.; McPhail, K.L.; Oishi, S. Design of coibamide A mimetics with improved cellular bioactivity. ACS Med. Chem. Lett. 2022, 13: 105-110. Published, 12/2022.
  • Mattos, D.R.; Wan, X.; Serrill, J.D.; Nguyen, M.H.; Humphreys, I.R.; Viollet, B.; Smith, A.B., III; McPhail, K.L.; Ishmael, J.E. The Marine-Derived Macrolactone Mandelalide A Is an Indirect Activator of AMPK. Mar. Drugs 2022, 20: 418. https://doi.org/10.3390/md20070418. Editor’s Choice. Published, 12/2022.
  • Loughran, R.M.; Diefendorf, C.M.; Reill-VanSise, J.R. et al. Streptomyces spiramenti sp. nov., isolated from a deep-sea microbial mat. Arch Microbiol 2022, 204: 717. https://doi.org/10.1007/s00203-022-03326-6. Published, 12/2022.
  • Mattos, D.R.; Weinman, M.A.; Wan, X.; Goodall, C.P.; Serrill, J.D.; McPhail, K.L.; Milovancev, M.; Bracha, S.; Ishmael, J.E. Canine osteosarcoma cells exhibit basal accumulation of multiple chaperone proteins and are sensitive to small molecule inhibitors of GRP78 and heat shock protein function. Cell Stress & Chaperones 2022, 27: 223-239. https://link.springer.com/article/10.1007/s12192-022-01263-3. Published, 12/2022.
  • Kazemi, S.; Kawaguchi, S.; Badr, C.E.; Mattos, D.R.; Ruiz-Saenz, A.; Serrill, J.D.; Moasser, M.M.; Dolan, B.P.; Paavilainen, V.O.; Oishi, S.; McPhail, K.L.; Ishmael, Jane E. Targeting of HER/ErbB family proteins using broad spectrum Sec61 inhibitors coibamide A and apratoxin A. Biochemical Pharmacology 2021, 183, 114317. Published, 12/2021.
  • Schmid, R.,Tehan, R., McPhail, K.L., Dorrestein, P.D. Ion Identity Molecular Networking in the GNPS Environment. Nat. Commun. 2021, 12, 3832. https://doi.org/10.1038/s41467-021-23953-9. Published, 12/2021.
  • Jarmusch, A.K., Wang, M., McPhail, K.L., Dorrestein, P.C. et al. ReDU: a framework to find and reanalyze public mass spectrometry data. Nat. Methods, 2020, 17(9), 901-904. https://www.nature.com/articles/s41592-020-0916-7. Published, 12/2020.
  • Tranter, D., Paatero, A.O., Kawaguchi, S., Kazemi, S., Serrill, J.D.; Kellosalo, J., Vogel, W.K., Richter, U., Mattos, D.R., Wan, X., Thornburg, C.C.; Oishi, S., McPhail, K.L.; Ishmael, J.E., Paavilainen, V.O. Coibamide A targets Sec61 to prevent biogenesis of secretory and membrane proteins. ACS Chemical Biology, 2020, 15, 8, 2125–2136. Published, 08/2020.
  • Loughran, R.M.; Mitchell, E.A.; Vining, O.B.; Gallegos, D.A.; Deadmond, M.C.; Wasson, B.J.; Pfannmuller, K.M.; Paddock, B.E.; Koyack, M.J.; Oline, D.K.; Ushijima, B.; Saw, J.H.; McPhail, K.L.; Videau, Patrick. Draft genome sequence of Streptomyces sp. strain ventii, isolated from a microbial mat near hydrothermal vents within the axial seamount in the Pacific Ocean, and resequencing of the type strains Streptomyces lonarensis NCL 716 and Streptomyces bohaiensis 11A07. Microbiology Resource Announcements, 2020, 9(32), e00607. https://mra.asm.org/content/9/32/e00607-20. Published, 12/2020.
  • Aron A.T.,* Gentry E.C.,* McPhail, K.L*…Dorrestein, P.D. et al. Reproducible molecular networking of untargeted mass spectrometry data using GNPS. Nat Protoc. 2020, 15(6):1954-1991. PubMed ID: 32405051. Published, 12/2020.