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LPI Faculty

Balz Frei, Ph.D.

Director and Endowed Chair, Linus Pauling Institute

Joan H. Facey Linus Pauling Institute Professor

Distinguished Professor, Department of Biochemistry and Biophysics

Office: 305 Linus Pauling Science Center

Telephone: (541) 737-5078

Fax: (541) 737-5077

Email Address: balz.frei@oregonstate.edu

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


Research Interests

The research program in my laboratory is aimed at understanding the role of free radicals and inflammation in human chronic diseases, in particular atherosclerosis and cardiovascular disease, and the ameliorating effects of micronutrients, phytochemicals, and dietary supplements.

One of the earliest events in atherosclerosis is “activation” of the endothelium, a single-cell layer lining arterial walls. Endothelial activation may be caused by increased production of free radicals and leads to increased expression of cellular adhesion molecules (CAM) and monocyte chemoattractant protein-1 (MCP-1) by these cells. As a consequence, white blood cells called monocytes are recruited to the arterial wall, where they initiate chronic inflammation and atherosclerotic lesion development. We are performing cell culture, animal, and human studies to investigate 1) the mechanisms and consequences of endothelial activation, 2) the role of transition metals like iron and copper in this process, and 3) the effectiveness of antioxidant and anti-inflammatory dietary compounds in ameliorating endothelial activation and subsequent atherosclerotic lesion development.

We have found that lipoic acid and certain metal chelators (metal-binding agents) effectively inhibit CAM and MCP-1 expression by human aortic endothelial cells and suppress vascular inflammation and atherosclerosis in experimental mice. We are currently performing two randomized clinical trials to investigate the effects of lipoic acid supplementation on oxidative stress, inflammation, serum lipids and lipoproteins, blood pressure, and other coronary risk factors in healthy subjects and heart disease patients.

Additional projects in the laboratory investigate the biological mechanisms and metabolic effects of flavonoids, the interactions of lipoic acid and ascorbic acid (vitamin C) in improving vitamin C body status and antioxidant defenses in humans, and the mechanisms of pharmacological doses of vitamin C in its potential cancer therapeutic effects.


Education

1983 M.S., Biochemistry, Swiss Federal Institute of Technology, Zürich (ETH-Z), Switzerland
1986 Ph.D., Biochemistry, Swiss Federal Institute of Technology, Zürich (ETH-Z), Switzerland
1987-90 Post-doc, Biochemistry, University of California, Berkeley

Professional Experience

1983-86 Ph.D. student, Swiss Federal Institute of Technology, Zürich, Switzerland
1987-90 Post-doctoral fellow, Division of Biochemistry and Molecular Biology, University of California, Berkeley, CA (Bruce N. Ames, sponsor)
1990 (summer) Visiting Scholar, The Heart Research Institute, Sydney, NSW, Australia
1990-94 Assistant Professor of Nutrition, Department of Nutrition, Harvard School of Public Health, Boston, MA
1992-94 Assistant Professor of Toxicology, Department of Molecular and Cellular Toxicology, Harvard School of Public Health, Boston, MA
1994-97 Associate Professor of Medicine and Biochemistry, Whitaker Cardiovascular Institute, Boston University School of Medicine, Boston, MA
1997-2010 Director and Endowed Chair, Linus Pauling Institute, and Professor, Biochemistry and Biophysics, Oregon State University, Corvallis, OR
2010-present Director and Endowed Chair, Linus Pauling Institute, and Distinguished Professor, Biochemistry and Biophysics, Oregon State University, Corvallis, OR

Recent Awards and Grants

2000 Conference Grant (R13), NIH "Gordon Conference on Oxygen Radicals in Biology"
2000 Research grant from PuriPonics, Portland, Oregon
2000-03 Research grant from The Washington Tree Fruit Research Commission
2000-05 P01 (PI, project 1), NIH/NHLBI "Vitamin C, glutathione, and endothelial activation"
2001-03 R03 (Co-PI), NIH/NIEHS "Mechanisms of PCP genotoxicity and antioxidant modulation"
2001-03 R03 (Co-PI), NIH/NIEHS "Lipoic acid, endothelial activation, and atherosclerosis"
2002 Dorothy Epstein Nutrition Fellow, Hunter College of the City University of New York
2003 Conference Grant (R13) "10th Annual SFRBM Meeting"
2003-08 P01 (Program Director, PI on project 1, Administrative Core Director) NIH/NCCAM "Center of Excellence for Research on Complementary and Alternative Medicine Antioxidant Therapies (CERCAT)"
2004 Conference Grant (R13) "11th Annual SFRBM Meeting"
2004 Annual Achievement Award in Preventive Medicine, American College for Advancement in Medicine
2004 Distinguished Service Award, Society for Free Radical Biology and Medicine
2005 Discovery Award, Medical Research Foundation, Oregon Health & Science University
2008-13 P01 (Program Director, PI on project 1, Administrative Core Director) NIH/NCCAM "Center of Excellence for Research on Complementary and Alternative Medicine Antioxidant Therapies (CERCAT)"

Professional Activities and Memberships

Editorial Boards

Archives of Biochemistry and Biophysics (1993-96)
Redox Report (1996-present)
Free Radical Biology & Medicine (1997-present)
FASEB Journal (2001-present)
American Journal of Clinical Nutrition (2002-2004)

Editor

"Natural Antioxidants in Human Health and Disease," Academic Press, San Diego, CA (1994)
Special Review Series "Molecular and Biological Mechanisms of Antioxidant Action," FASEB J. 13, Nos. 9 & 10 (1999)
Co-Editor "The Antioxidant Vitamins C and E," AOCS Press, Champaign, IL (2002)

NIH

Site Visit Team, "Oxidative Events in Cancer Therapy" (P-01), University of Iowa (1994)
Special Emphasis Panel (ZRG4-NTN-5R), Nutrition Study Section (1995)
Temporary Reviewer, Metabolism Study Section (1998)
Special Emphasis Panel (ZRG2 NMS), Metabolism Study Section (1998)
Temporary Reviewer, Pathology A Study Section (2000-03)
Program Review "Oxidation in Inflammation and Cardiovascular Disease (P01) (2003)
Temporary Reviewer, Atherosclerosis and Inflammation of the Cardiovascular System (AICS) Study Section (2004-05)
Charter Member, AICS Study Section (2005-08)
Program Review, "Biobehavioral Bases of CHD Risk and Management" (P01) (2005)

American Heart Association

National Center, Lipoprotein and Lipid Metabolism Peer Review Committee (1997-00)
Fellow (F.A.H.A.), Council on Arteriosclerosis

Chair

FASEB Conference "Molecular and Biological Mechanisms of Antioxidant Action," Copper Mountain, CO (1998)
11th Gordon Research Conference on "Oxygen Radicals in Biology," Ventura, CA (2000)
Linus Pauling Institute Conference "Diet and Optimum Health", Portland, OR (2001, 2003, 2005, 2009)
Linus Pauling Institute Conference "Diet and Optimum Health", Corvallis, OR (2011, 2013)
10th Annual Meeting of the Society for Free Radical Biology & Medicine, Seattle, WA (2003)
11th Annual Meeting of the Society for Free Radical Biology & Medicine, St. Thomas, Virgin Islands (2004)
President, The Society for Free Radical Biology & Medicine (2002-04); President-elect (2000-02); Treasurer (1997-00)


Research Projects

P01 AT002034 (Frei)
NIH/NCCAM
Center of Excellence for Research on Complementary and Alternative Medicine Antioxidant Therapies (CERCAT)
Period: 09/26/03-05/31/13
The goals of CERCAT are to better understand the molecular and cellular mechanisms of action and to test the in vivo efficacy – both in experimental animals and humans – of redox-active CAM modalities, in particular alpha-lipoic acid, that have the potential to substantially improve the body’s resistance to chronic disease and aging. These goals will be accomplished through three highly interactive projects: 1. "Lipoic acid supplementation to reduce risk factors for atherosclerosis in humans" (Dr. Balz Frei, Project Leader); 2. "Lower vulnerability to toxins in aging by treatment with lipoic acid" (Dr. Tory Hagen); and 3. "CAM antioxidants in amyotrophic lateral sclerosis" (Dr. Joseph Beckman).
Roles: Program Director, Project 1 Leader, and Administrative Core Director

T32 AT002688 (Oken)
NIH/NCCAM
CAM: Neuroscience and Stress
Period: 04/01/10-03/31/15
The major goal of this grant is to train graduate students and post-doctoral fellows in basic and applied research related to complementary medicine and either neurology or stress, including oxidative/nitrative and toxicological stresses.
Role: PI on Oregon State University subcontract, Training Faculty

Research Grant (Frei)
USANA Health Sciences, Inc.
Biological and Health Effects of Bioflavonoids
Period: 04/01/10–03/31/11
The goal of this study is to characterize the inhibitory effects (Ki and IC50) of natural extracts and authentic polyphenols on digestive enzyme activities, including alpha-amylase, alpha-glucosidase, and pancreatic lipase; and to investigate the effects of select polyphenols on carbohydrate and fat absorption, insulin sensitivity, and markers of inflammation and oxidative stress in humans.
Role: PI

Research Grant (Frei)
USANA Health Sciences, Inc.
Effects of Lipoic Acid Supplementation on Vitamin C Metabolism, Antioxidant Status, and Inflammatory Markers in Human Volunteers
Period: 04/01/10–03/31/11
The primary purpose of this study is to investigate whether lipoic acid can increase vitamin C steady-state concentrations in plasma and peripheral blood mononuclear cells and increase the retention of vitamin C in the body by increasing its reabsorption in the kidneys.
Role: PI


Recent Publications

Lykkesfeldt J, Michels AJ, Frei B. (2014) Vitamin C. Adv Nutr 5:16-18.

Frei B. (2013) The case is far from closed for vitamin and mineral supplements! Comment on: Enough is enough: Stop wasting money on vitamin and mineral supplements. Ann Intern Med.

Michels AJ, Frei B. (2013) Myths, artifacts, and fatal flaws: identifying limitations and opportunities in vitamin C research. Nutrients 5:5161-5192.

Wei H, Zhang WJ, Leboeuf R, Frei B. (2013) Copper induces - and copper chelation by tetrathiomolybdate inhibits - endothelial activation in vitro. Redox Rep 2013 [Epub ahead of print].

Rodriguez KJ, Wong HK, Oddos T, Southall M, Frei B, Kaur S. (2013) A purified Feverfew extract protects from oxidative damage by inducing DNA repair in skin cells via a PI3-kinase-dependent Nrf2/ARE pathway. J Dermatol Sci 72:304-310.

Michels AJ, Hagen TM, Frei B. (2013) Human genetic variation influences vitamin C homeostasis by altering vitamin C transport and antioxidant enzyme function. Annu Rev Nut 33:45-70.

Dixon BM, Barker T, McKinnon T, Cuomo J, Frei B, Borregaard N, Gombart AF. (2012) Positive correlation between circulating cathelicidin antimicrobial peptide (hCAP18/LL-37) and 25-hydroxyvitamin D levels in healthy adults. BMC Res Notes 5:575.

Wei H, Zhang WJ, McMillen TS, Leboeuf RC, Frei B. (2012) Copper chelation by tetrathiomolybdate inhibits vascular inflammation and atherosclerotic lesion development in apolipoprotein E-deficient mice. Atherosclerosis 223:306-313.

Frei B,, Birlouez-Aragon I, Lykkesfeldt J. (2012) Authors' perspective: What is the optimum intake of vitamin C in humans? Crit Rev Food Sci Nutr 52:815-829.

Yilmazer-Musa M, Griffith AM, Michels AJ, Schneider E, Frei B. (2012) Grape seed and tea extracts and catechin 3-gallates are potent inhibitors of α-amylase and α-glucosidase activity. J Agric Food Chem 60:8924-8929.

Finlay LA, Michels AJ, Butler JA, Smith EJ, Monette JS, Moreau RF, Petersen SK, Frei B, Hagen TM. (2012) R-alpha-lipoic acid does not reverse hepatic inflammation of aging, but lowers lipid anabolism, while accentuating circadian rhythm transcript profiles. Am J Physiol Regul Integr Comp Physiol 302:R587-597.

Wei H, Frei B,, Beckman JS, Zhang WJ. (2011) Copper chelation by tetrathiomolybdate inhibits lipopolysaccharide-induced inflammatory responses in vivo. Am J Physiol Heart Circ Physiol 301:H712-720.

Lotito SB, Zhang WJ, Yang CS, Crozier A, Frei B. (2011) Metabolic conversion of dietary flavonoids alters their anti-inflammatory and antioxidant properties. Free Radic Biol Med 51:454-463.

Zhang WJ, Wei H, Tien YT, Frei B. (2011) Genetic ablation of phagocytic NADPH oxidase in mice limits TNFa-induced inflammation in the lungs but not other tissues. Free Radic Biol Med 50:1517-1525.

Zhu BZ, Mao L, Fan RM, Zhu JG, Zhang YN, Wang J, Kalyanaraman B, Frei B. (2011) Ergothioneine prevents copper-induced oxidative damage to DNA and protein by forming a redox-inactive ergothioneine-copper complex. Chem Res Toxicol 24:30-34.

Bowman GL, Shannon J, Ho E, Traber MG, Frei B, Oken BS, Kaye JA, Quinn JF. (2011) Reliability and validity of food frequency questionnaire and nutrient biomarkers in elders with and without mild cognitive impairment. Alzheimer Dis Assoc Disord 25:49-57.