Assistant Professor of Medicinal Chemistry
Principal Investigator, Linus Pauling Institute
Department of Pharmaceutical Sciences
College of Pharmacy
Oregon State University
203 Pharmacy Building
Corvallis, OR 97331-3507
Phone: 541-737-9534
fred.stevens@oregonstate.edu
Affiliations: Linus Pauling Institute
Mass Spectrometry Facility Web site
Institute of Plant Biochemistry, Halle, Germany; Postdoctoral Research Associate, 2000–2002.
Free University of Amsterdam; Postdoctoral Research Associate, 1999–2000.
Oregon State University; Postdoctoral Research Associate, 1995–1999.
University of Groningen, The Netherlands; Ph.D. 1995, Pharmacy license 1990; M.Sc. 1988.
Our research group is interested in the areas of bio-organic chemistry, natural products chemistry and toxicology. Mass spectrometry is an important technique in our laboratory for studying small organic molecules in complex biological matrices such as blood plasma, tissue homogenates and plant extracts.
Our main research project focuses on the interactions of biological antioxidants with lipid peroxidation products, which are formed through radical-mediated oxygenation of polyunsaturated lipids. We are interested in these interactions because lipid peroxidation contributes to the development and progression of chronic inflammatory and age-related diseases. Our laboratory has identified vitamin C (ascorbic acid) as a biological nucleophile that has the ability to form Michael-type conjugates with electrophilic lipid peroxidation products. We are studying vitamin C conjugation (‘ascorbylation’) as a novel pathway for elimination of reactive lipid peroxidation products. The goal of our research is to establish ascorbylation of oxidized lipids as a physiological response to oxidative stress for diagnostic and therapeutic purposes. The tools that we use for our research include liquid chromatography coupled to mass spectrometry for analysis of lipid conjugates in complex biological matrices, synthesis of (labeled) lipids and their conjugates, cell culture for investigating the biological properties of oxidized lipids and their conjugates and animal models for studying the in vivo disposition, metabolism and excretion of oxidized lipids. This research project is being pursued in collaboration with Balz Frei and Maret Traber of the Linus Pauling Institute at OSU.
Lipid peroxidation products may cause cellular damage by covalently binding to proteins. In collaboration with Claudia Maier of OSU’s Chemistry Department and Tory Hagen of the Linus Pauling Institute, we are developing quantitative methods based on isotope dilution mass spectrometry to examine the nature and the extent of mitochondrial protein modifications by lipid peroxidation products in the aging heart. By using these proteomics-based methods, we will be able to investigate the molecular basis of age-related mitochondrial dysfunction, a key factor in the development of congestive heart failure.
Fred Stevens also has interests in the field of natural products isolation and structure elucidation. He and his colleagues at OSU have explored the chemistry and biology of prenylated flavonoids of the hop plant (Humulus lupulus) since 1995. Currently, he collaborates with Jonathan Page (Plant Biotechnology Institute, Saskatoon, Canada) on the biosynthesis of xanthohumol and related prenylated flavonoids using biochemical and genomics approaches.
Marley K, Mooney DT, Clark-Scannell G, Tong TT, Watson J, Hagen TM, Stevens, JF, Maier CS. Mass tagging approach for mitochondrial thiol proteins. Journal of Proteome Research. 2005;4:1403-1412.
Sowell J, Frei B, Stevens JF. Vitamin C conjugation of genotoxic lipid peroxidation products: Structural characterization and detection in human plasma. Proceedings of the National Academy of Sciences. 2004;101:17964-17969.
Stevens JF, Page JE. Molecules of Interest. Xanthohumol and related prenylflavonoids in hops and beer: to your good health! Phytochemistry. 2004;65:1317-1330 (invited review).
Stevens JF, Miranda CL, Frei B, Buhler DR. Inhibition of peroxynitrite-mediated LDL oxidation by prenylated flavonoids: The a,ß-unsaturated keto functionality of 2'-hydroxychalcones as a novel antioxidant pharmacophore. Chemical Research in Toxicology. 2003;16:1277-1286.
Wollenweber E, Stevens JF, Klimo K, Knauft J, Frank N, Gerhäuser C. Cancer chemopreventive in vitro activities of isoflavones isolated from Iris germanica. Planta Medica. 2003;69:15-20.
Stevens JF, Miranda CL, Wolthers KR, Schimerlik M, Deinzer ML, Buhler DR. Identification and in vitro biological activities of hop proanthocyanidins: Inhibition of nNOS activity and scavenging of reactive nitrogen species. Journal of Agriculture and Food Chemistry. 2002;50:3435-3443.
Rodriguez RJ, Miranda CL, Stevens JF, Deinzer ML, Buhler DR. Influence of prenylated and non-prenylated flavonoids on liver microsomal lipid peroxidation and oxidative injury in rat hepatocytes. Food and Chemical Toxicology. 2001;39:437-445.
Yilmazer M, Stevens JF, Buhler DR. In vitro glucuronidation of xanthohumol, a flavonoid in hop and beer, by rat and human liver microsomes. FEBS Letters. 2001;491:252-256.
Yilmazer M, Stevens JF, Deinzer ML, Buhler DR. In vitro biotransformation of xanthohumol, a flavonoid from hops (Humulus lupulus), by rat liver microsomes. Drug Metabolism and Disposition. 2001;29:223-231.
Miranda CL, Aponso GLM, Stevens JF, Deinzer ML, Buhler DR. Prenylated chalcones and flavanones as inducers of quinone reductase in mouse Hepa 1c1c7 cells. Cancer Letters. 2000;149:21-29.
Henderson MC, Miranda CL, Stevens JF, Deinzer ML, Buhler DR. In vitro inhibition of human P450 enzymes by prenylated flavonoids from hops, Humulus lupulus. Xenobiotica. 2000;30:235-251.
Stevens JF, Taylor AW, Nickerson GB, Ivancic M, Henning J, Haunold ML, Deinzer ML. Prenylflavonoid variation in Humulus lupulus: distribution and taxonomic significance of xanthogalenol and 4'-O-methylxanthohumol. Phytochemistry. 2000;53:759-775.
Miranda CL, Stevens JF, Ivanov V, McCall M, Frei B, Deinzer ML, Buhler DR. Antioxidant and prooxidant actions of prenylated and nonprenylated chalcones and flavanones in vitro. Journal of Agriculture and Food Chemistry. 2000;48:3876-3884.
Miranda CL, Yang Y-H, Henderson MC, Stevens JF, Santana-Rios G, Deinzer ML, Buhler DR. Prenylflavonoids from hops inhibit the metabolic activation of the carcinogenic heterocylcic amine, 2-amino-3-methylimidazo[4,5-f]quinoline, mediated by cDNA-expressed human CYP1A2. Drug Metabolism and Disposition. 2000;28:1297-1302.
Milligan SR, Kalita JC, Pocock V, Van De Kauter V, Stevens JF, Deinzer ML, Ron H, De Keukeleire D. The endocrine activities of 8-prenylnaringenin and related hop (Humulus lupulus) flavonoids. Journal of Clinical Endocrinology & Metabolism. 2000;85:4912-4915.
Stevens JF, Taylor AW, Deinzer ML. Quantitative analysis of xanthohumol and related prenylflavonoids in hops and beer by liquid chromatography-tandem mass spectrometry. Journal of Chromatography A. 1999;832:97-107.
Miranda CL, Stevens JF, Helmrich A, Henderson MC, Rodriguez RJ, Yang Y-H, Deinzer ML, Barnes DW, Buhler DR. Antiproliferative and cytotoxic effects of prenylated flavonoids from hops (Humulus lupulus) in human cancer cell lines. Food and Chemical Toxicology. 1999;37:271-285.
Stevens JF, Ivancic M, Deinzer ML, Wollenweber E. A novel 2-hydroxyflavanone from Collinsonia canadensis. Journal of Natural Products. 1999;62:392-394.
Stevens JF, Ivancic M, Hsu VL, Deinzer ML. Prenylflavonoids from Humulus lupulus. Phytochemistry. 1997;44:1575-1585.
