The Oberlies research group focuses on the isolation and structure elucidation of bioactive compounds from natural sources, including filamentous fungi, predator bacteria, and plants. Such studies have ramifications both in the realm of drug discovery (in search of new anticancer and/or antibiotic agents) and in the area of herbal drugs (developing reference standards and studying herb-drug interactions).
Nature has been a valuable source for new drugs, particularly in the anticancer and antibiotic arenas, where nearly 60% of all currently used pharmaceuticals are either derived directly or based upon a natural product. We have several projects that seek to identify new drug leads. For our largest project, we are exploring a library of filamentous fungi, which have the advantage that they can be grown in culture, for new anticancer leads. This research is part of a Program Project, supported by the National Cancer Institute, where other team members are searching for similar leads from both cyanobacteria and plants. We have identified several promising leads from filamentous fungi, and studies are ongoing to isolate and determine the structures of the anticancer constituents. Under a separate project, we are collaborating with colleagues at Virginia Tech and the Jordan University of Science and Technology to study a group of bacteria, termed ‘predator bacteria’. These organisms rise to the top of the bacterial food chain and kill other bacteria as a sole source of nutrients. We are using predator bacteria via a chemical ecology approach toward the identification of new antibiotic leads. Another project in the realm of drug discovery examines plants for new leads that are active in the central nervous system. The common theme for all of these projects is the use of natural substances to identify small molecules that affect biological systems.
The tools and the skill sets that my group develops in the realm of drug discovery are directly applicable to working with herbal drugs. The only difference is that the end goals between these projects are somewhat different. With herbal drugs, we are often developing reference standards, such that the herbal mixture can be characterized more fully. Also, in one of our newest projects, we are working with colleagues at the University of North Carolina at Chapel Hill to understand potential untoward interactions that may occur between a pharmaceutical and an herbal material taken concomitantly. For that project, we are using assays for metabolism (p450s) to direct the purification of compounds. The common theme for our herbal projects is using natural products chemistry to better understand how an herbal products works while making it safer and more consistent for consumers.
Researchers working on projects in my group develop skills in analytical chemistry, spectroscopy/spectrometry, and organic chemistry. Chromatographic skills are honed to purify small molecules from crude extracts. Spectroscopy and spectrometry (particularly NMR and MS) are used to determine the structures of the isolated compounds de novo. The general principles of organic chemistry are used both to understand and predict chromatographic purifications and to assemble structures in a logical manner. Moreover, researchers in my group must develop an understanding and appreciation of biological assays and the biological effects of purified natural products.
Graf, T.G.; Levine, K.E.; Andrews, M.E.; Perlmutter, J.M.; Nielsen, S.J.; Davis, J.M.; Wani, M.C.; and Oberlies, N.H. (2007) Variability in the yield of benophenathridine alkaloids in wildcrafted vs cultivated bloodroot (Sanguinaria canadensis L.). J. Agricul. Food Chem. 55, 1205-1211.
Trembath, D.G.; Lal, A.; Kroll, D.J.; Oberlies, N.H. and Riggins, G.J. (2007) A novel small molecule that selectively inhibits glioblastoma cells expressing EGFRvIII. Molecular Cancer 6:30; doi:10.1186/1476-4598-6-30; http://www.molecular-cancer.com/content/6/1/30
Phifer, S. S.; Lee, D.; Seo, E. K.; Kim, N. C.; Graf, T. N.; Kroll, D. J.; Navarro, H. A.; Izydore, R. A.; Jimenez, F.; Garcia, R.; Rose, W. C.; Fairchild, C. R.; Wild, R.; Soejarto, D. D.; Farnsworth, N. R.; Kinghorn, A. D.; Oberlies, N. H.; Wall, M. E. and Wani, M. C. (2007) Alvaradoins E-N, antitumor and cytotoxic anthracenone C-glycosides from the leaves of Alvaradoa haitiensis. J. Nat. Prod. 70, 954-961.
Deep, G.; Oberlies, N.H.; Kroll, D.J.; and Agarwal, R. (2007) Isosilybin B and isosilybin A inhibit growth, induce G1 arrest and cause apoptosis in human prostate cancer LNCaP and 22Rv1 cells. Carcinogenesis 28, 1533-1542.
Nun, T. K.; Kroll, D. J.; Oberlies, N. H.; Soejarto, D. D.; Case, R. J.; Piskaut, P.; Matainaho, T.; Hilscher, C.; Wang, L.; Dittmer, D. P.; Gao, S. J. and Damania, B. (2007) Development of a fluorescence-based assay to screen antiviral drugs against Kaposi's sarcoma associated herpesvirus. Mol. Cancer Ther. 6, 2360-2370.
Alali, F.; Tawaha, K.; El-Elimat, T.; Syouf, M.; El-Fayad, M.; Abulaila, K.; Nielsen, S. J.; Wheaton, W. D.; Falkinham III, J. O. and Oberlies, N. H. (2007) Antioxidant activity and total phenolic content of aqueous and methanolic extracts of Jordanian plants: an ICBG project Nat. Prod. Res. 21, 1121-1131.
Graf, T. N.; Wani, M. C.; Agarwal, R.; Kroll, D. J. and Oberlies, N. H. (2007) Gram-scale purification of flavonolignan diastereoisomers from Silybum marianum (Milk Thistle) extract in support of preclinical in vivo studies for prostate cancer chemoprevention. Planta Med. 73, 1495-1501.
Oberlies, N. H.; Li, C.; McGivney, R. J.; Alali, F. Q.; Tanner, J. R. and Falkinham, J. O., III. (2008) Microbial-mediated release of bisphenol A from polycarbonate vessels. Lett. Appl. Microbiol. 46, 271-275.
Deep, G.; Oberlies, N. H.; Kroll, D. J. and Agarwal, R. (2008) Isosilybin B causes androgen receptor degradation in human prostate carcinoma cells via PI3K-Akt-Mdm2-mediated pathway Oncogene 27, 3986-3998.
Deep, G.; Oberlies, N. H.; Kroll, D. J. and Agarwal, R. (2008) Identifying the differential effects of silymarin constituents on cell growth and cell cycle regulatory molecules in human prostate cancer cells Int. J. Cancer 123, 41-50.
Alali, F. Q.; Gharaibeh, A.; Ghawanmeh, A.; Tawaha, K. and Oberlies, N. H. (2008) Colchicinoids from Colchicum crocifolium Boiss.: A case study in dereplication strategies for (-)-colchicine and related analogs using LC-MS and LC-PDA techniques. Phytochem. Anal. 19, 385-394.
Alali, F.Q.; Tahboub, Y.R.; Ibrahim, E.S.; Qandil, A.M.; Tawaha, K; Burgess, J.P.; Sy, A.; Nakanishi; Y.; Kroll, D.J.; and Oberlies, N.H. (2008) Pyrrolizidine alkaloids from Echium glomeratum (Boraginaceae). Phytochemistry 69, 2341-2346.
Oberlies, N. H.; Rineer, J. I.; Alali, F. Q.; Tawaha, K.; Falkinham III, J. O. and Wheaton, W. D. (2009) Mapping of sample collection data: GIS tools for the natural product researcher. Phytochemistry Lett. 2, 1-9.
Ngo, N.; Yan, Z.; Graf, T. N.; Carrizosa, D. R.; Kashuba, A. D.; Dees, E. C.; Oberlies, N. H. and Paine, M. F. (2009) Identification of a cranberry juice product that inhibits enteric CYP3A-mediated first-pass metabolism in humans. Drug Metab. Dispos. 37, 514-522.
Falkinham, J. O. III., T. E. Wall, J. R. Tanner, K. Tawaha, F. Q. Alali, C. Li, and Oberlies, N.H. (2009) Proliferation of antibiotic-producing bacteria and concomitant antibiotic production as the basis for the antibiotic activity of Jordan’s Red Soils. Appl. Environ. Microbiol. 75, 2735-2741.
NIH PubMed Publications for Nicholas Oberlies