OHSU

Academics & Training

CAM Research Training

The Oregon Center for Complementary and Alternative Medicine in Neurological Disorders has a T32 institutional training grant, "CAM Research Training in Neuroscience and Stress", from the National Center for Complementary and Alternative Medicine at NIH. Dr. Barry Oken is the director of the training grant. This training grant provides funding for predoctoral students in the Behavioral Neuroscience Department at Oregon Health & Science University (OHSU) and for postdoctoral fellows with an interest in complementary medicine and either neurology or stress, including oxidative/nitrative and toxicologic stress. Complementary medicine is a broad area and includes treatments such as dietary supplements and mind-body medicine as well as others (see http://nccam.nih.gov/health/whatiscam/ for fuller description of CAM).

 

Mentoring Resources

OHSU Lead Mentorship Program: www.ohsu.edu/mentoring

 

Individual Mentoring Plan:

Individual Development Plan from the AAAS sponsored, Burroughs Welcome Fund, UCSF, Medical College of Wisconsin and FASEB

http://myidp.sciencecareers.org

 

National Institutes of Health: NIH postdoc Handbook: http://www.history.nih.gov/research/downloads/stetten fellow handbook.pdf

 

American Psychological Association: Centering on Mentoring: http://www.apa.org/education/grad/mentor-task-force.aspx

 

University of California SF mentorship reources:

http://accelerate.ucsf.edu/training/mdp-materials

 

University of Minnesota mentorship course:

http://www.ctsi.umn.edu/education/Mentoring/index.htm 

 

University of Wisconsin, Institute for Clinical and Translational Research mentorship resources:

https://mentoringresources.ictr.wisc.edu

 

Mentors List

All applicants must select a mentor from the following list. Primary mentors must have a significant history of prior mentorship and of CAM research. If the mentor selected does not have this level of experience in both areas, a co-mentor with primary experience in the other area that is lacking will also need to be established.

Joe Beckman, Ph.D.

Linus Pauling Institute, OSU

The Beckman lab investigates the dark side of nitric oxide – how nitric oxide interacts with superoxide (O2.-) and other radicals to form much stronger oxidants such as peroxynitrite (ONOO-) and how peroxynitrite modulates signal transduction. We developed antibodies to nitrotyrosine, which is now a widely used marker for the role of nitric oxide-derived oxidants, particularly peroxynitrite, in biology and pathology. A major interest in the lab is to understand how mutations to the copper, zinc superoxide dismutase (SOD) gene can cause Lou Gehrig's disease, also known as amyotrophic lateral sclerosis. The lab is currently investigating the role of zinc in protecting transgenic mice against the toxicity of ALS-mutant SOD. The Beckman lab is also investigating the effects of a common pesticide, metam sodium, on cell function. This is closely related to a common inhibitor of Cu,Zn superoxide dismutase and may also affect activation of NFkB.

Dennis Bourdette, M.D.

Neurology Department, OHSU

Dr. Bourdette is Chair of the Department of Neurology at OHSU as well as a staff neurologist at the Portland VA Medical Center. He is also Director of the Multiple Sclerosis (MS) Center of Oregon and co-Director of the MS Center for Excellence-West located at the Portland VA Medical Center. His area of special interest is the immunopathogenesis and treatment of multiple sclerosis and other neuroimmunologic diseases. His NCCAM funded research through ORCCAMIND involved evaluating the effect of several natural antioxidants on a mouse MS model. The finding that alpha lipoic acid produces significant clinical improvement in the mouse by inhibiting T-cell migration into the CNS has resulted in significant follow-up research including an ongoing clinical trial. Other current CAM-related research includes a clinical trial of ginkgo biloba on cognitive function in MS and assessing several botanicals for their effect on neurite growth in vitro.

Gene Bowman, ND, MPH

Neurology Department, OHSU; Nestle Institute of Health Sciences, EPFL, Lausanne, Switzerland

The lab exploits a systems biology approach to propose, initiate and advance the biomedical research on neuronal metabolism.  We investigate novel models and translatable targets aimed at preserving brain health, preventing cognitive decline and neurodegeneration.  Large-scale functional genomics and mass spectrometry capabilities are integrated with bioinformatics and metabolic systems biology to generate holistic molecular insights into nutritionally actionable conditions at the genomic, proteomic and metabonomic levels.  This is served in part by an NIH/NIA R01 to examine the effects of omega-3 fatty acids on neurovascular mechanisms that modulate age-related cognitive decline.  Using an integrated system approach we ultimately aspire to develop nutritional interventions that promote healthy aging and cognitive health.  The lab has capacity to provide basic (cell/animal) and applied research (epidemiology/clinical trials) experiences at OHSU and NIHS.    

Christopher Cunningham, Ph.D.

Behavioral Neuroscience Department OHSU

This lab is generally concerned with motivational effects of abused drugs, with special emphasis on genetic and brain mechanisms underlying drug-seeking and drug-taking behavior. These studies involve various animal genetic models, including selectively bred mouse lines, recombinant inbred strains, congenic strains, and knockout/transgenic strains. Behavioral procedures commonly used include: operant self-administration, place conditioning (preference and aversion), and taste conditioning. In some projects, studies are designed to identify and characterize the physiological, neuroanatomical, neurochemical and molecular systems that mediate drug reward and aversion. These studies may involve systemic or intracranial administration of pharmacological agents (e.g., receptor agonists or antagonists). Other studies, done in collaboration with OHSU faculty colleagues, examine molecular changes produced by drug exposure. The lab is also engaged in projects that examine the roles played by environment, experience and learning. Of special relevance to this training program are studies that address the role of Pavlovian conditioning and other cognitive processes on the response to drugs, including “placebo” responses. For example, in a recent collaborative project with Drs. Richard Jones, Barry Oken and Dennis Bourdette, the beneficial impact of Pavlovian conditioning on the therapeutic response to ALA (alpha lipoic acid, thioctic acid) in mice with paralytic autoimmune encephalomyelitis (EAE) has been examined.

Balz Frei, Ph.D.

Linus Pauling Institute, OSU

The research program in the Frei laboratory is aimed at understanding the mechanisms of oxidative stress in human disease, in particular atherosclerosis, and the ameliorating effects of dietary and metabolic antioxidants, dietary supplements, and metal chelators. One of the earliest events in atherosclerosis is endothelial dysfunction with increased expression of adhesion molecules and monocyte chemoattractants. As a consequence, monocytes are recruited to the arterial wall, where they initiate an inflammatory response and give rise to lipid-laden foam cells. The lab is 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 in this process, and the effectiveness of ascorbic acid, lipoic acid, and other antioxidants in ameliorating endothelial dysfunction. Recent work in the Frei laboratory has shown that metal chelators and lipoic acid, but not ascorbic acid or glutathione, can inhibit the expression of adhesion molecules and monocyte chemoattractant peptide-1 in human aortic endothelial cells. The lab is now studying the cellular mechanisms underlying these beneficial effects on endothelial function, in particular inhibition of redox-sensitive cell signaling and transcription factors (NFB, Sp-1, and AP-1). In addition, the lab is studying whether metal chelators and lipoic acid can exert anti-inflammatory and anti-atherogenic effects in transgenic mouse models by inhibiting adhesion molecule and MCP-1 expression. These studies will also address the question of whether chelation therapy with EDTA or desferrioxamine (Deferal®), currently used in CAM, is safe and efficacious in inhibiting atherosclerosis. The interdisciplinary nature of our studies results in collaborations with Drs. Hagen and Beckman, who are investigating the role of lipoic acid, metal chelators, and other “CAM antioxidants” in aging and amyotrophic lateral sclerosis, respectively. The ultimate goal of these collaborative studies, which are funded by a NCCAM program project grant, is to provide the essential knowledge about the underlying mechanisms, dose-response effects, and relevant biological targets to advance these CAM therapies to human trials; and, equally important, to test for untoward effects that might discourage CAM antioxidant therapies from proceeding to human studies.

Adrian Gombart, PhD

Linus Pauling Institute, OSU

The research the Gombart lab is focused on understanding the regulation of antimicrobial peptide expression by the vitamin D pathway. When immune cells called macrophages encounter a pathogen and become activated, the vitamin D pathway is turned on, leading to the induction of the cathelicidin antimicrobial peptide if serum levels of vitamin D are sufficient. This mechanism is conserved in humans and primates but not in other mammals. The lab developed a transgenic mouse that carries the human cathelicidin gene. Using this model, the lab is testing the ability of vitamin D to protect against infection by influenza, Salmonella, and Mycobacterium tuberculosis. Another focus of the lab is to identify additional dietary compounds that regulate the expression of the cathelicidin gene. This gene is also induced by sodium butyrate and lithocholic acid, which functions through the vitamin D receptor. Nutrients that bind the vitamin D receptor may modulate the immune system by inducing the cathelicidin gene. The lab discovered that curcumin in curry modestly induces expression of the cathelicidin gene, which could protect the gut from infection. A small molecule library screen for regulators of the cathelicidin gene identified resveratrol and pterostilbene as inducers of cathelicidin gene expression. Finally, the lab is interested in determining the effect of vitamin D on the function of the innate immune system in the elderly. Aging is accompanied by low-grade, chronic, systemic inflammation, and vitamin D has important anti-inflammatory properties. Research is focused on determining if sufficient levels of vitamin D will reduce the inflammatory phenotype.

Mitchell Haas, DC

Western States Chiropractic College

Dr. Haas has collaborated with Dr. Oken in mind-body medicine as a co-investigator on the yoga study in ORCCAMIND and through a pilot trial that included a placebo model for immediate pain relief following spinal manipulation. He is co-investigator in Dr. Oken’s U19 application to study expectancy and a R01 proposal to study stress reduction with mindfulness meditation for caregivers of Alzheimer’s disease patients. Dr. Haas has further been a PI on a study of self-management of back pain in the elderly, including evaluation of the effect of improved self-efficacy on back pain (R18 HP10012). He has extensive research experience in chiropractic management of pain and diagnostic procedures for determining manipulative therapy.

Tory Hagen, Ph.D.

Linus Pauling Institute, OSU

The Hagen lab investigates two interrelated and fundamental aspects of aging: 1) the causes and consequences of mitochondrial decay in cardiovascular aging, and 2) the mechanisms associated with loss of oxidative stress resistance in the elderly. Moreover, the lab seeks to identify “age-essential” micronutrients, which can improve/maintain mitochondrial function and/or increase resistance to oxidative insult. The lab has shown age-related changes in the mitochondria in the aging rat heart, brain and vascular endothelial cells in terms of reduced levels of glutathione and vitamin C, a lower thiol/disulfide ratio, heightened levels of oxidative damage and lower indices of mitochondrial bioenergetic parameters. However, dietary addition of R-a-lipoic acid (LA) reverses much of the increase in indices of oxidative stress while dietary supplementation with acetyl-L-carnitine maintains bioenergetic parameters, particularly in the aging rat brain and myocardium. With regards to altered stress resistance, the lab has shown that feeding LA to old rats reverses the age-related increased susceptibility to toxic insult (tert-butylhydroperoxide and menadione). Because LA is rapidly metabolized in the cell, we hypothesized that it may be acting as a signaling molecule to upregulate stress response mechanisms. We found that LA works by inducing the nuclear translocation of a transcription factor, Nrf2, which in turn, initiates expression of over 300 genes involved in oxidative/toxicological stress response in the cell. These findings thus have large ramifications for overall resistance to pathophysiological insult, which otherwise declines with age. These studies are in concert with those of Drs. Balz Frei and Joseph Beckman, who along with the Hagen lab, have been awarded a P01 (NCCAM) to examine antioxidants, such as LA, on cardiovascular and neurological disorders.

William Hersh, M.D.

Medical Informatics And Clinical Epidemiology Department, OHSU

Dr. Hersh performs research in a variety of areas related to medical informatics and evidence-based medicine. His major area of focus is information retrieval, which investigates the optimal means for the production, organization, retrieval, and evaluation of scientific literature. Dr. Hersh has a great deal of experience developing retrieval systems as well as evaluating them in the hands of real users. He also has performed systematic reviews and evidence reports about telemedicine and other informatics-related topics. Dr. Hersh also has much experience with educational technologies and serves as the director of OHSU's distance learning programs in medical informatics. He directed the education and information transfer core for ORCCAMIND and has participated in the Cochrane Collaboration complementary medicine group.

Fay Horak, Ph.D.

Neurological Sciences Institute, OHSU

Dr. Horak studies neural control of posture and gait and the effects of neurological disorders in order to improve balance rehabilitation. Of particular interest are changes in postural strategies in the elderly and in patients with pathologies common in the elderly: Parkinson’s disease, cerebellar ataxia, vestibular loss, and peripheral neuropathy. Studies involve quantification of body motions, surface forces and muscle activation patterns in response to controlled perturbations of stance and gait and the ability to adapt to altered environmental conditions. Her laboratory also investigates the effectiveness of medications, surgeries and new approaches including Alexander Technique to rehabilitation on balance disorders and back pain. Dr. Horak leads a sensorimotor control journal club and lectures in a Behavioral Neuroscience course on Multisystem Understanding of Aging. Her studies have direct application to improving the diagnosis and rehabilitation of balance disorders to prevent falls in the elderly.

Steven Johnson, M.D, Ph.D.

Neurology Department OHSU

The Johnson laboratory uses electrophysiological techniques to study the neuropharmacology dopamine in the brain. Using an animal model of Parkinson's disease, we are actively studying effects of dopamine neurodegeneration on the synaptic pharmacology of deep brain structures such as the subthalamic nucleus. Another current project investigates effects of environmental toxins, such as pesticides and herbicides, on physiological membrane properties of dopamine neurons. Other projects have investigated the actions of dietary supplements, such as gamma-hydroxybutyrate and ephedra, on dopamine neurophysiology.

Kim Dupree Jones, Ph.D.

School of Nursing, OHSU

Dr. Jones heads an inter-professional team of fibromyalgia researchers and clinicians studying fibromyalgia. She is particularly interested in  neuroendocrine axis perturbations that can be modified by exercise, drug or selected CAM therapies (yoga and Tai chi). Physiologic measures include exercise treadmill (V02 max) induced growth hormone, cortisol, IGF-1. More recently she has employed computerized dynamic posturography, nociceptive reflex testing and quantitative sensory testing. She is an author on the Fibromyalgia Impact Questionnaire-Revised, the gold standard functionality/symptom management questionnaire. She oversees a database of over 5,000 patients with American College of Rhuematology confirmed diagnosis of fibromyalgia. She is the PI or Co-PI on over $6 million in externally funded fibromyalgia studies from NIH, Industry and Foundations. She is also the president of the Fibromyalgia Information Foundation, a non-profit organization dedicated to bias free dissemination of research and clinical standards.

Jeffrey Kaye, M.D.

Neurology Department, OHSU

Dr. Kaye is Professor of Neurology and Director of the NIA funded Layton Aging and Alzheimer’s Disease Center at Oregon Health and Science University. Dr. Kaye’s research program has focused over the past decade on the research question of why some individuals remain protected from dementia at advanced ages while others succumb at much earlier times. In order to answer this question he has emphasized the high-risk population of people at age 85 or older (the “oldest old”). The centerpiece of these studies has been the ongoing Oregon Brain Aging Study, established in 1989. This study has made several original contributions pertaining to exceptional aging ranging from defining the role of health in delaying cognitive decline to discovery of presymptomatic markers of cognitive decline related to brain volumes, cognitive performance and genetic risk. In this context, most recently in collaboration with the Oregon Center for Complementary and Alternative Medicine in Neurological Disorders and funded by NCCAM he has been investigating the role of standardized ginkgo biloba extract in preventing dementia in cognitively intact octogenarians. This is the first such study to apply biomarkers to the study of dementia prevention. Dr. Kaye has also conducted similar studies in Alzheimer’s disease patients where he has served as a mentor to junior investigators studying CAM compounds such as cats claw and lactoferrin.

Suzanne Mitchell, PhD

Behavioral Neuroscience Department, OHSU

Dr. Mitchell's group examines whether drug users' higher impulsivity rate than non-drug users existed prior to drug use, or is a consequence of the neuroadaptations due to drug use.  To address these questions, they work with human, rat and mouse subjects.  For example, they examine whether different genotypes are associated with impulsive behavior by comparing impulsivity in drug-naïve selected lines and inbred strains of mice and rats.  They also examine whether different levels of impulsivity predict responses the first time mice and rats are exposed to drugs of abuse, like alcohol, nicotine and methamphetamine.  Measures of impulsivity in human subjects are used to examine whether acute exposure to drugs of abuse or withdrawal form use results in changes in behavior.  In addition, Dr. Mitchell's research examines the basic neural processes involved in decision making, including impulsive and risky decision making, using lesion techniques and imaging.

Cynthia Morris, Ph.D., M.P.H.

Medical Informatics And Clinical Epidemiology Department, OHSU

Dr. Morris is assistant dean for admissions OHSU School of Medicine and Vice-Chair of the Department of Medical Informatics and Clinical Epidemiology, with dual appointments in the Departments of Medicine and Public Health and Preventive Medicine. As an epidemiologist, she has extensive experience in clinical trials, population?based studies, patient registries, and systematic reviews. Dr. Morris has directed the Biostatistics and Study Design Core of the ORCCAMIND project, and through this, she has coordinated the major trials as well as all the smaller, developmental studies in complementary and alternative medicine. From this endeavor, Dr. Morris recently developed a new Clinical Research Data Resource at OHSU for trial coordination and the maintenance and establishment of practice networks for research. Her principal research focus has been in the etiology of congenital malformations. She established the Oregon Registry of Congenital Heart Defects, the only population-based registry of its kind in the US; she also has established a research focus on the role of folate intake and metabolism in congenital heart disease. She is a member of the Oregon Evidence-Based Practice Center, and performed the systematic review on which recommendations from the US Preventive Task Force on antioxidant supplementation for cancer and heart disease prevention are based. Dr. Morris established and directs the NIH K30 funded Human Investigations Program to train faculty in fellows in clinical research. Thus far, more than 85 faculty have enrolled in the program's first three certificate cohorts, including 6 complementary and alternative medicine practitioners from outside OHSU (National College of Naturopathic Medicine, Oregon College of Oriental Medicine). From this K30 program, Dr. Morris has recently proposed a Master of Clinical Research degree that has been approved at all level at OHSU and is now awaiting final approval by the Oregon University System for implementation in fall, 2004. Dr. Morris has a long record of mentoring physicians and medical students pursuing an MPH at OHSU; in addition, she is the primary mentor for one K23 grantee at OHSU, and is actively working with three others for K23 development. She serves on the Board of Directors of the Association of Clinical Research Training Program Directors Association.

John Nutt, M.D.

Neurology Department, OHSU

Dr. Nutt and the Movement Disorders Group focus on movement disorders with particular interest in Parkinson’s disease, gait disorders of the elderly, and experimental therapeutics of movement disorders. These interests have led to studies of coenzyme Q10 in Parkinson’s disease, effects of diet and exercise on response to levodopa in Parkinson’s disease and Kava-Kava in Huntington’s disease. Current studies examine the effects of inhibition of the dopamine transporter on the response to levodopa and the effects of infusion of glial derived neurotrophic factor (GDNF) into the striatum of patients with Parkinson’s disease.

Barry Oken, M.D.

Neurology Department, OHSU

The lab has a long history of trying to better understand the mechanisms underlying the age-related decline in human cognition, primarily visual attention, with particular emphasis on those mechanisms that may be remediable. The lab is currently studying the effects of mind-body medicine, including yoga, meditation and expectancy or placebo effects, on human cognition and physiology. Projects include both interventional as well as mechanistic studies. The current studies maintain the emphasis on aging. Human subjects for the experiments are healthy young adults, healthy older adults, and older adults with diseases neurodegenerative disorders e.g., Alzheimer’s and Parkinson's disease. Dr. Oken has a long-standing interest in human neurophysiology focusing on EEG and evoked potentials. Physiologic markers for stress are a major current interest. Assessments include experimental cognitive tasks using accuracy, reaction time, conventional clinical neuropsychologic tests, personality traits, fatigue and quality of life. Physiologic measures include conventional EEG, digital EEG signal analysis, event-related potentials, autonomic nervous system activity (e.g., heart rate variability),and scanpaths.

Joseph Quinn, MD

Neurology Department, OHSU

Dr. Quinn's research program utilizes animal models and human "biomarker" studies for the purpose of developing strategies for prevention and treatment of Alzheimer's disease, with a focus on oxidative damage as a treatable mechanism. Anti-inflammatory and antioxidant strategies have been studied in a transgenic mouse model of AD (Tg2576), and are currently being examined in human trials employing cerebrospinal fluid disease markers. The biomarker strategy reduces the numbers of subjects necessary for "proof of concept" trials, and permits conclusions regarding the biological basis of treatment efficacy, conclusions which are not possible in traditional clinical trials based solely on cognitive outcomes. The animal model strategy also permits the screening of combination therapy, which is not practical in the clinical setting. The animal studies are currently focused on co-enzyme Q and a copper-chelating agent, with plans to explore combination therapy with agents previously proven effective, including alpha lipoic acid and ibuprofen. The focus is on agents which are already approved for use in clinical trials, so that the animal studies may be quickly translated to clinical trials.

Charles Roselli, Ph.D.

Physiology and Pharmacology Department, OHSU

The lab is studying the effects of complementary herbal medicines on neuroendocrine reproductive function and prostate cancer. Projects include both in vivo animal studies and in vitro mechanistic studies. Currently we are studying the effects of Saw Palmetto (Serenoa repens) berry extract on IGF-1 signaling pathways in human prostate cell lines. We have also assessed the effects of the prostate herbal mixture PC-SPES on the neuroendocrine axis of rats. The laboratory uses a variety of experimental techniques, including hormone evaluations, molecular and cell biological techniques to measure phosphylation states of signaling molecules, gene expression, and enzymatic activities.

Lynne Shinto, N.D., M.P.H.

Neurology Department, OHSU

Center for Women's Health, OHSU  

Dr. Shinto's research focuses on evaluating complementary and alternative medicine (CAM) therapies in chronic neurologic disorders.  Specific interests are in evaluating clinical and immunomodulatory effects of omega-3 fatty acids and antioxidants (alpha lipoic acid) in people with multiple sclerosis and Alzheimer's disease (respectively).  Dr. Shinto is also interested in evaluating quality of life and pain in patients that visit clinics that utilize both CAM and conventional providers and therapies.   

Amala Soumyanath, Ph.D.

Neurology Department, OHSU

Amala Soumyanath  has a B.Pharm degree and Ph.D. both from the University of London, UK.  Her area of expertise is "Pharmacognosy", the scientific study of medicinal plants. Dr. Soumyanath joined the faculty of OHSU Neurology Department in 2003, through ORCCAMIND – the Oregon Center for Complementary and Alternative Medicine in Neurological Diseases. She is currently also affiliated with the Layton Aging and Alzheimer's Disease Center at OHSU.

Dr Soumyanath's research encompasses the characterization and quality control of botanicals, phytochemical isolation, preclinical and clinical evaluation of botanical extracts, and bioavailabilty and pharmacokinetic studies of  the active compounds in botanicals. The goals of her research are to (a) validate and understand the traditional use of botanicals through scientific study, and (b) investigate botanicals as a source of new treatments for disease.  Her current research focus is on the Ayurvedic herb, Centella asiatica. Recent studies in collaboration with neuroscientists and neurologists at OHSU, have shown that Centella asiatica extracts may stimulate peripheral nerve regeneration and also be useful as a neuroprotective agent in central nervous system. Preclinical and clinical studies are currently being pursued on the use of Centella asiatica extracts in the treatment of diabetic neuropathy, Alzheimer's Disease and mild cognitive impairment.  Maret Traber, Ph.D.

Fred Stevens, PhD

Linus Pauling Institute, OSU

The research mission of the Stevens Lab is to determine the role of phytochemicals and vitamins in preventing or treating age-related diseases, including cardiovascular and metabolic diseases. This research group develops LC-MS/MS methods for targeted and untargeted metabolomics experiments to determine the biological effects of phytochemicals/vitamins in supplementation/deficiency studies using cell culture, animal models and humans. The lab has developed novel biomarkers to examine the role of oxidative stress and the protective effects of dietary supplements in human health and disease. One research project aims to elucidate the mechanisms by which xanthohumol, a prenylated flavonoid from the hops plant (Humulus lupulus), mitigates abnormal glucose and lipid metabolism in animal models of obesity. Using an untargeted metabolomics approach, the group discovered that oral administration of xanthohumol to obese rats leads to reduced formation of lipotoxicity products by improving beta-oxidation of fatty acids. Dr. Stevens has studied the chemistry and biology of xanthohumol since 1997 and has published 22 papers on this compound. Other projects in the lab focus on the role of vitamin C in the prevention of tolerance to nitrate therapy and on the development of bioherbicides and skin care products derived from the enzymatic degradation of glucosinolates naturally present in meadowfoam (Limnanthes alba), an oilseed crop grown in the Willamette Valley of Oregon.

Maret Traber, PhD

Linus Pauling Institute, OSU

This laboratory investigates the function and bioavailability of vitamin E in humans. To define alpha-tocopherol functions at the molecular level, several tools are available. The lab uses different forms of vitamin E to test specific functions. For example, despite having identical antioxidant activities, natural and synthetic alpha-tocopherols are utilized differently, because they have different stereochemistries. The alpha-tocopherol transfer protein (TTP) in liver is critical in this regard. We have developed an alpha-TTP-knockout mouse in which the gene for this protein has been deleted. Hence, this mouse is unable to discriminate between natural and synthetic alpha-tocopherols. Plans are underway to use this mouse to define specific molecular functions and pathways that are susceptible to alpha-tocopherol deficiency. Additionally, other naturally occurring forms of vitamin E, such as gamma-tocopherol and the tocotrienols, are being investigated to assess whether they have specific roles in human nutrition. Studies of vitamin E metabolism serve to determine whether there is sufficient vitamin E in the face of oxidative stress. Preliminary data in smokers and extensive exercisers who are under increased oxidative stress suggest that oxidative stress increases the need for vitamin E. Studies of the kinetics of deuterated tocopherols in smokers compared with non-smokers, or in athletes during exercise and at rest, will allow assessment of the vitamin E requirements and their relationship to vitamin E metabolites. The availability of deuterated tocopherols has now made it possible to carry out extensive measurements of the biokinetics and bioavailability of vitamin E in humans. The Traber laboratory has developed new methodologies using liquid chromatography-mass spectrometry that are 100-fold more sensitive than previous methods. The purpose of these measurements is to detail the requirements of normal humans and those with diseases related to oxidative stress, such as atherosclerosis, cancer, diabetes and Alzheimer's disease.

Vivek Unni, MD, Ph.D.

Parkinson's & Movement Disorders, OHSU

The lab is interested in understanding the mechanisms of neurodegeneration that occur in Parkinson's Disease (PD) and related disorders. Specifically, we are interested in the role of the protein alpha-synuclein. Several lines of evidence suggest that overexpression of this protein can lead to the formation of alpha-synuclein aggregates that are toxic to brain cells and lead to the symptoms of PD. Our approach has been to use mouse models that overexpress alpha-synuclein to study this process in the living brain, using advanced fluorescence microscopy techniques, like multiphoton imaging. Projects include testing the possible role of genetic influences and environmental toxins that have been implicated in PD on alpha-synuclein aggregation. We are also testing the ability of the natural product curcumin, the active compound in the spice turmeric, to remove preformed aggregates. The lab uses a variety techniques to complement our in vivo imaging work, including protein biochemistry, immunohistochemistry, and animal behavior.

 

T32 Executive Committee

Barry Oken, MD, Professor, Neurology Dept, Oregon Health & Science University

Dennis Bourdette, MD, Chair, Neurology Dept, Oregon Health & Science University

Heather Zwickey, PhD, Director, Helfgott Research Institute; Research Dean and Professor of Immunology, National College of Natural Medicine

Chris Cunningham, PhD, Professor, Behavioral Neuroscience Dept, Oregon Health & Science University

Balz Frei, PhD, Director and Professor, Linus Pauling Institute at Oregon State University

OHSU and OSU are Equal Opportunity/Affirmative Action Employers