Tim Bugni's research interests are marine natural products chemistry, symbiotic microorganisms, drug discovery, metabolomics, and NMR and MS for structure elucidation of novel natural products.

Genetically encoded small molecules, natural products, have been a valuable source of therapeutics particularly in the areas of cancer and infectious disease. However, discovering novel natural products has become significantly more difficult even though whole genome sequencing has shown that only a small fraction of microbial-produced natural products have been discovered. To overcome these difficulties, we are utilizing under-explored niches for bacterial cultivation and developing metabolomics approaches to enable discovery of novel natural products. We have cultivated bacteria from marine invertebrates such as sponges and ascidians. Many of these bacteria show great promise as sources of novel therapeutics. Using metabolomics, we prioritize the most promising strains for discovery of novel natural products as therapeutics in the areas of neurodegenerative disease, infectious disease, and cancer. For additional information, please see the lab website.

The overarching goal of our long-term research plan is to develop diverse natural product libraries from unique microbes for the purposes of drug discovery. Identification of novel therapeutic leads provides opportunities for synthetic modification to understand and relate the structure to a biological response and alter the pharmacological properties. Exploring lead compounds not only in terms of drug development, but also in terms of chemical biology and molecular pharmacology will provide opportunities to produce chemical probes that can be used to investigate cellular function.

Tim received his bachelor's degree in chemistry from MT Tech in 1995 and a Ph.D. degree from the University of Utah with Professor Chris M. Ireland. He held a postdoctoral appointment at Scripps Institution of Oceanography (2003-4), and was a research assistant professor at the University of UT from 2004-2009. He joined the faculty at the School of Pharmacy in 2009. His research interests are marine natural products chemistry, symbiotic microorganisms, drug discovery, metabolomics, and NMR and MS for structure elucidation of novel natural products.

Professional Interests: Marine natural products chemistry, structure elucidation of novel natural products using NMR and MS, drug discovery, metabolomics.

Education:

• BS 1995 Chemistry - Montana Tech of the University of Montana
• PhD 2003 - University of Utah
• Postdoc 2004 - Scripps Institution of Oceanography

1. Chanana, S.; Thomas, C. S.; Zhang, F.; Braun, D. R.; Rajski, S.; Bugni, T. S. HCA/PCA pipeline in R for untargeted metabolomics. Metabolites 2020, 10, E297.  PMCID:  In process
2. Thomas, C. S.; Braun, D. R.; Omos, J. L.; Rajski, S. R.; Phillips, G. N.; Andes, D.; Bugni, T. S. Pyridine 2,6 dithiocarboxylic acid and metal complexes:  New inhibitors of new delhi metallo-beta-lactamse 1.  Marine Drugs 2020, 18, 295.  PMCID:  PMC7374359
3. Zhang, F.; Braun, D. R.; Rajski, S. R.; DeMaria, D.; Bugni, T. S. Enhypyrazinones A and B, pyrazinone natural products from a marine-derived myxobacterium, Enhygromyxa sp. Mar. Drugs 2019, 17, pii:E698. PMCID:  PMC6950740
4. Yan, J. X.; Chevrette, M. G.; Braun, D. R.; Harper, M. K.; Currie, C. R., Bugni, T. S. Madurastatin D1 and D2, Oxazoline containing siderophores isolated from an Actinomadura sp. Org. Lett. 2019, 21, 6275-6279. PMCID:  PMC6941472
5. Acharya, D. D.; Miller, I. J.; Cui, Y.; Braun, D. R.; Berres, M.; Styles, M. J.; Li, L.; Kwan, J.; Rajski, S. R.; Blackwell; Bugni, T. S. Omics technologies to understand activation of a biosynthetic gene cluster in Micromonospora sp. WMMB235: Deciphering keyicin biosynthesis. ACS Chem. Biol. 2019, 14, 1260-1270.  PMCID:  PMC6591704
6. Chevrette, M. G.; Carlson, C. M.; Ortega, H. E.; Thomas, C.; Ananiev, G. E.; Barns, K. J.; Cagnazzo, J.; Carlos, C.; Flanigan, W.; Grubbs, K. J.; Horn, H. A.; Hoffman, F. M.; Klassen, J. L.; Knack, J. J.; Lewin, G. R.; McDonald, B. R.; Muller, L.; Melo, W. G. P.; Pinto-Tomas, A. A.; Schmitz, A.; Wendt-Pienkowski, E.; Wildman, S.; Zhao, M.; Zhang, F.; Bugni, T. S.; Andes, D. R.; Pupo, M. T.; Currie, C. R. New antibiotics from insect microbiomes. Nature Communications 2019, 10, 516.  PMCID:  PMC6355912
7. Zhang, F; Braun, D. R.; Ananieve, G. E.; Hoffmann, F. M.; Tsai, I-W.; Rajski, S. R.; Bugni, T. S. Biemamides A-E, inhibitors of the TGF-beta pathway that block the epithelial to mesenchymal transition. Org. Lett. 2018, 20, 5529-5532. PMCID:  PMC6207949
8. Adnani, N.; Chevrette, M. G.; Adibhatla, S. N.; Zhang, F.; Yu, Q.; Braun, D. R.; Nelson, J.; Simpkins, S. W.; McDonald, B. R.; Myers, C. L.; Piotrowski, J.; Thompson, C. J.; Currie, C. R.; Li, L.; Rajski, S. R.; Bugni, T. S. Co-culture of marine invertebrate-associated bacteria and interdisciplinary technologies enable biosynthesis and discovery of a new antibiotic keyicin.  ACS Chem. Bio. 2017, 12, 3093-3102.  PMCID:  PMC5973552
9. Wyche, T. P.; Alvarenga, R. F. R.; Piotrowski, J. S.; Duster, M. N.; Warrack, S.; Cornilescu, G.; De Wolfe, T. J.; Hou, Y.; Braun, D.; Ellis, G. A.; Simpkins, S. W.; Nelson, J.; Myers, C. L.; Steele, J. L.; Mori, H.; Safdar, N.; Markley, J. L.; Rajski, S. R.; Bugni, T. S. Chemical genomics, structure elucidation, and in vivo studies of the marine-derived anticlostridial ecteinamycin. ACS Chem. Bio. 2017, 12, 2287-2295. PMCID:  PMC5697710
10. Cornilescu, G.; Alvarenga, R. F. R.; Wyche, T. P.; Bugni, T. S.; Gil, R. R.; Cornilescu, C. C.; Westler, W. M.; Markley, J. L.; Schweiters, C. D. Progressive stereo-locking (PSL) - A residual dipolar coupling based force field method for determining the relative configuration of natural products and other small molecules. ACS Chem. Bio. 2017, 12, 2157-2163. PMCID: PMC5712214
11. Chanana, S.; Thomas, C. S.; Braun, D. R.; Hou, Y.; Wyche, T. P.; Bugni, T. S. Natural product discovery using planes of principal component analysis in R (PoPCAR). Metabolites. 2017, 7, pii: E34.  PMCID:  PMC5618319
12. Ellis, G. A.; Thomas, C. S.; Chanana, S.; Adnani, N.; Szachowicz, E.; Braun, D. R.; Harper, M. K.; Wyche, T. P.; Bugni, T. S. Brackish habitat dictates cultivable actinobacterial diversity from marine sponges. PLoS One. 2017, 12, e0176968. PMCID: PMC5503172
13. Zhang, Y.; Adnani, N.; Braun, D. R.; Ellis, G. A.; Barns, K. J.; Parker-Nance S.; Guzei, I. A.; Bugni, T. S. Micromonohalimanes A and B: Antibacterial halimane-type diterpenoids from a marine Micromonospora species. J. Nat. Prod. 2016, 79, 2968-2972. PMCID:  PMC5159749
14. Zhang, F.; Adnani, N.; Vazquez-Rivera, E.; Braun, D. R.; Tonelli, M.; Andes, D. R.; Bugni, T. S. Application of 3D NMR for structure determination of peptide natural products. J. Org. Chem., 2015, 80, 8713-8719.  PMCID:  PMC4696765
15. Wyche, T. P.; Piotrowski, J. S.; Hou, Y.; Braun, D. R.; Deshpande, R.; McIlwain, S. J.; Ong, I. M.; Myers, C. L.; Westler, W. M.; Andes, D. R.; Bugni, T. S. Forazolines A and B: Novel natural products with in vivo efficacy against Candida albicans. Angew. Chem. Int. Ed., 2014, 53, 11583-11586.  PMCID:  PMC4215405