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
| 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 |
The research program in my laboratory is aimed at understanding the mechanisms of oxidative stress in atherosclerosis and coronary artery disease (CAD), and the ameliorating effects of dietary and metabolic antioxidants, dietary supplements, and metal chelators. One of the earliest events in atherosclerosis is dysfunction of the endothelium, leading to recruitment of monocytes to the arterial wall. Once trapped in the arterial wall, monocytes initiate an inflammatory response and eventually give rise to lipid-laden foam cells. In addition, endothelial dysfunction is associated with decreased nitric oxide synthesis and impaired vasodilation, which are important causal factors in hypertension. We are performing biochemical, cell biological, and animal studies to investigate the mechanisms and consequences of endothelial dysfunction, the role of pro-oxidant transition metals like iron and copper, and the effectiveness of ascorbic acid, lipoic acid, and other antioxidants in ameliorating endothelial dysfunction.
In collaboration with investigators at Boston University School of Medicine, we have discovered that vitamin C improves endothelial function and vasodilation in patients with CAD or coronary risk factors, and lowers blood pressure in moderately hypertensive patients. Work in our laboratory using human aortic endothelial cells has shown that metal chelators, lipoic acid, and flavonoids, but not vitamin C or glutathione, can inhibit the expression of endothelial adhesion molecules, which are responsible for monocyte recruitment to the arterial wall. We are now studying the cellular mechanisms underlying these beneficial effects on adhesion molecule expression, in particular inhibition of redox-sensitive cell signaling mechanisms and transcription factor activation. In addition, we are studying whether metal chelators and lipoic acid can exert anti-inflammatory and anti-atherogenic effects in transgenic mouse models by inhibiting adhesion molecule expression. These studies will also address the question of whether chelation therapy with EDTA or desferrioxamine (Deferal®), currently used in complementary and alternative medicine, is safe and efficacious in inhibiting atherosclerosis.
We also have discovered that consumption of fructose-rich foods, such as apples and fruits in general, causes plasma levels of uric acid to increase. Uric acid is a metabolic antioxidant, the potential health effects of which are poorly understood. While excessive uric acid levels cause gout, elevated uric acid levels have been associated with protection against multiple sclerosis and rheumatoid arthritis. In contrast, uric acid has been claimed to be an independent risk factor for CAD, but the evidence is inconclusive and controversial. Therefore, we are planning to examine the role of uric acid in endothelial adhesion molecule expression, inflammation, and atherosclerosis. Uric acid may also inhibit the degradation of extracellular matrix proteins in atherosclerotic lesions, which might prevent these lesions from rupturing and causing a myocardial infarction or stroke. The ultimate goal of our studies is to better understand the mechanisms of endothelial dysfunction and atherosclerosis and to find new, effective strategies to prevent and treat CAD by diet, dietary supplements, and therapeutic agents.
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)
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
Zhang WJ, Wei H, Frei B (2009) Genetic deficiency of NADPH oxidase does not diminish, but rather enhances, LPS-induced acute inflammatory responses in vivo. Free Radic Biol Med 46:791-798.
Bowman GL, Dodge H, Frei B, Calabrese C, Oken BS, Kaye JA, Quinn JF. (2009) Ascorbic acid and rates of cognitive decline in Alzheimer's disease. J Alzheimers Dis 16:93-98.
Li L, Frei B (2009) Prolonged exposure to LPS increases iron, heme, and p22phox levels and NADPH oxidase activity in human aortic endothelial cells: inhibition by desferrioxamine. Arterioscler Thromb Vasc Biol 29:732-738.
Roberts LJ 2nd, Traber MG, Frei B (2009) Vitamins E and C in the prevention of cardiovascular disease and cancer in men. Free Radic Biol Med 46:1558.
Bowman GL, Shannon J, Frei B, Kaye JA, Quinn JF (2010) Uric acid as a CNS antioxidant. J Alzheimers Dis 19:1331-1336.
Traber MG, Frei B. (2010) Micronutrient concentrations and subclinical atherosclerosis in adults with HIV. Am J Clin Nutr 92:266-267.
Zhang WJ, Wei H, Frei B. (2010) The iron chelator, desferrioxamine, reduces inflammation and atherosclerotic lesion development in experimental mice. Exp Biol Med 235:633-641.
Michels AJ, Hagen TM, Frei B. (2010) A new twist on an old vitamin: human polymorphisms in the gene encoding the sodium-dependent vitamin C transporter 1. Am J Clin Nutr 92:271-272.
Li L, Smith A, Hagen TM, Frei B. (2010) Vascular oxidative stress and inflammation increase with age: ameliorating effects of alpha-lipoic acid supplementation. Ann N Y Acad Sci 1203:151-159.
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.
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.
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.
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 51:454-63.
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.
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.
