Photo of Fred StevensPrincipal Investigator, Linus Pauling Institute 
Professor of Medicinal Chemistry, Department of Pharmaceutical Sciences, College of Pharmacy

Office: 435 Linus Pauling Science Center
Telephone: 541-737-9534
Fax: 541-737-5077
Email Address: fred.stevens@oregonstate.edu

Mailing/Express Delivery Address:
Fred Stevens, Ph.D.
Linus Pauling Institute
Oregon State University
307 Linus Pauling Science Center
Corvallis, OR 97331

Research Interests

Our research group has interests 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, cell lysates, tissue homogenates, and plant extracts.

Bioconjugation of oxidized lipids

This research project aims to determine how vitamin C interacts with lipid peroxidation products and how vitamin C prevents cellular damage to proteins caused by oxidized lipids. We are interested in these interactions because lipid peroxidation contributes to the development and progression of chronic inflammatory and age-related diseases, such as atherosclerosis. Our laboratory has identified vitamin C (ascorbic acid) as a biological nucleophile able to form Michael adducts with lipid-derived 2-alkenals. This reaction may be of interest as a detoxification pathway for 2-alkenals. 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 formation, metabolism and excretion of oxidized lipids.

In collaboration with Professor Claudia Maier of OSU’s Chemistry Department, we are developing quantitative methods based on isotope dilution mass spectrometry to examine the nature and the extent of protein modifications by lipid peroxidation products in cultured cells and animal models of oxidative stress. One of our main findings is that vitamin C, at physiologically relevant concentrations, prevents adduct formation of oxidized lipids with cellular proteins. The significance of this finding is that vitamin C may help maintain proper function of metabolizing and transporter proteins, thus mitigating the deleterious effects of oxidized lipids.

Structure elucidation and biological activity of natural products

Our laboratory has also interests in the field of natural products isolation and structure elucidation. We have explored the chemistry and biology of prenylated flavonoids of the hop plant (Humulus lupulus) since 1995. We were the first to report that the principal prenylated flavonoid in hops, xanthohumol, exerts anti-inflammatory and cancer chemopreventive activities. Our current aim is to determine whether and how xanthohumol improves dysfunctional lipid and glucose metabolism in humans diagnosed with metabolic syndrome.

Another research project in our laboratory is focused on the chemistry and biology of natural products from the oilseed crop, meadowfoam (Limnanthes alba). The Oregon oilseed industry produces a high-quality oil from meadowfoam seeds that is used in personal care products. Considered useless in the past, the seed waste may prove of value as a natural herbicide in organic farming. We have developed a fermentation procedure for enhancing the herbicidal activity of the seed waste by converting inactive seedmeal glucosinolates into degradation products with herbicidal activity.

Education

2000-2002 Postdoctoral Research Associate degree, Institute of Plant Biochemistry, Halle, Germany
1999-2000 Postdoctoral Research Associate, Free University of Amsterdam
1995-1999 Postdoctoral Research Associate, Oregon State University (OSU)
1995 Ph.D. University of Groningen, The Netherlands
1990 Pharmacy license, University of Groningen, The Netherlands
1988 M.Sc., University of Groningen, The Netherlands

Professional Experience

2015-present Professor of Medicinal Chemistry, Department of Pharmaceutical Sciences, OSU
2009-2015 Associate Professor of Medicinal Chemistry, Department of Pharmaceutical Sciences, OSU
2008-present Co-Director, Mass Spectrometry Core, Environmental and Health Sciences Center, OSU
2005-present Principal Investigator, Linus Pauling Institute, OSU
2005-2009 Assistant Professor of Medicinal Chemistry, Department of Pharmaceutical Sciences, OSU
2002-2004 Assistant Professor (Sr. Res.), Department of Chemistry, OSU
2000-2002 Staff Scientist/Group Leader, Institute of Plant Biochemistry, Halle a/d Saale, Germany
1999-2000 Research Associate, Department of Bioorganic Chemistry, Free University of Amsterdam, The Netherlands

Awards and Honors

2008-09 Guest Professor (course on medicinal natural products), University of Antwerp, Belgium
2007 Teacher of the Year Award, Oregon State College of Pharmacy
2004 Beginning Grant-in-Aid Award, American Heart Association
1995 Ph.D. Cum Laude
1989 F.H.L Van Os Award, Society for Medicinal Plant Research (The Netherlands)

Professional Activities and Memberships

Member

Royal Pharmaceutical Society of the Netherlands (1990-present)
American Society of Mass Spectrometry (1996-present)
Phytochemical Society of North America (1997-present)
American Society of Pharmacognosy (2005-present)
American Heart Association (2004-present)

Reviewer for funding agencies

Netherlands Organization for Scientific Research (NWO, The Hague, 2005)
North Carolina Biotechnology Center (2007)
Bicentennial Program for Science and Technology, CONICYT (Reviewer and Site Visitor, Santiago, Chile, 2006-present)

Reviewer

Phytochemistry (1998-present)
Journal of Agricultural and Food Chemistry (1998-present)
Chemical Research in Toxicology (2004-9)
Journal of Mass Spectrometry (2004)
Planta Medica (2005)
Nature Chemical Biology (2005-9)
Cancer Letters (2006)
Free Radical Research (2006), Alcohol (2006)
Biochemistry (2006)
British Journal of Nutrition (2007)

Editorial Board

Molecular Nutrition and Food Research (2005)

Recent Publications

Elie MR, Choi J, Nkrumah-Elie YM, Gonnerman GD, Stevens JF, Tanguay RL. (2015) Metabolomic analysis to define and compare the effects of PAHs and oxygenated PAHs in developing zebrafish. Environ Res 140:502-510.

Choi J, Leonard SW, Kasper K, McDougall M, Stevens JF, Tanguay RL, Traber MG. (2015) Novel function of vitamin E in regulation of zebrafish (Danio rerio) brain lysophospholipids discovered using lipidomics. J Lipid Res 56:1182-1190.

Atwell LL, Hsu A, Wong CP, Stevens JF, Bella D, Yu TW, Pereira CB, Löhr CV, Christensen JM, Dashwood RH, Williams DE, Shannon J, Ho E. (2015) Absorption and chemopreventive targets of sulforaphane in humans following consumption of broccoli sprouts or a myrosinase-treated broccoli sprout extract. Mol Nutr Food Res 59:424-433.

Farley SM, Leonard SW, Stevens JF, Traber MG. (2014) Deuterium-labeled phylloquinone fed to α-tocopherol-injected rats demonstrates sensitivity of low phylloquinone-containing tissues to menaquinone-4 depletion. Mol Nutr Food Res 58:1610-1619.

Intanon S, Reed RL, Stevens JF, Hulting AG, Mallory-Smith CA. (2014) Identification and phytotoxicity of a new glucosinolate breakdown product from Meadowfoam (Limnanthes alba) seed meal. J Agric Food Chem 62:7423-7429.

Gray NE, Morré J, Kelley J, Maier CS, Stevens JF, Quinn JF, Soumyanath A. (2014) Caffeoylquinic acids in Centella asiatica protect against amyloid-ß toxicity. J Alzheimers Dis 40:359-373.

Lebold KM, Kirkwood JS, Taylor AW, Choi J, Barton CL, Miller GW, Du JL, Jump DB, Stevens JF, Tanguay RL, Traber MG. (2014) Novel liquid chromatography-mass spectrometry method shows that vitamin E deficiency depletes arachidonic and docosahexaenoic acids in zebrafish (Danio rerio) embryos. Redox Biol 172:105-113.

Humpf HU, Schneider C, Stevens JF. (2014) Functional food--where do we go? Mol Nutr Food Res 58:5-6.

Legette L, Karnpracha C, Reed RL, Choi J, Bobe G, Christensen JM, Rodriguez-Proteau R, Purnell JQ, Stevens JF. (2014) Human pharmacokinetics of xanthohumol, an antihyperglycemic flavonoid from hops. Mol Nutr Food Res 58:248-55.

Kirkwood JS, Legette LL, Miranda CL, Jiang Y, Stevens JF. (2013) A metabolomics-driven elucidation of the anti-obesity mechanisms of xanthohumol. J Biol Chem 288:19000-19013.

Kirkwood JS, Maier C, Stevens JF. (2013) Simultaneous, untargeted metabolic profiling of polar and nonpolar metabolites by LC-Q-TOF mass spectrometry. Curr Protoc Toxicol Chapter 4:Unit 4.39.

Wang Z, Kirkwood JS, Taylor AW, Stevens JF, Leid M, Ganguli-Indra G, Indra AK. (2013) Transcription factor Ctip2 controls epidermal lipid metabolism and regulates expression of genes involved in sphingolipid biosynthesis during skin development. J Invest Dermatol 133:668-676.

Legette LL, Luna AY, Reed RL, Miranda CL, Bobe G, Proteau RR, Stevens JF. (2013) Xanthohumol lowers body weight and fasting plasma glucose in obese male Zucker fa/fa rats. Phytochem 91:236-241.

Kirkwood JS, Lebold KM, Miranda CL, Wright CL, Miller GW, Tanguay RL, Barton CL, Traber MG, Stevens, JF. (2012) Vitamin C deficiency activates the purine nucleotide cycle in zebrafish. J Biol Chem 287:3833-3841

Zasada IA, Weiland JE, Reed RL, Stevens JF. (2012) Activity of meadowfoam (Limnanthes alba) seed meal glucolimnanthin degradation products against soilborne pathogens. J Agric Food Chem 60:339-345.

Legette L, Ma L, Reed RL, Miranda CL, Christensen JM, Proteau RR, Stevens JF. (2012) Pharmacokinetics of xanthohumol and metabolites in rats after oral and intravenous administration. Molec Nutr Food Res 56:466-474.