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Linus Pauling Institute Life-Income Gifts SPRING/SUMMER 2014 Oregon State University The Linus Pauling Institute RESEARCH NEWSLETTER From the Director Metabolizing Balz Frei, Ph.D. Drugs and Toxins LPI Director and Endowed Chair Distinguished Professor of An Interview with Biochemistry and Biophysics Sharon Krueger, Ph.D. Joan H. Facey LPI Professor Assistant Professor (Senior Research) n my last column I told you about the strategic Q. Where did you earn your doctorate? I planning process that the Linus Pauling Institute A. I earned my doctorate in genetics and crop science from embarked on about a year ago and promised to update Oregon State University. you on the emerging key goals and initiatives. We are now in the process of finalizing the plan, which will be released Q. Did you work on plant breeding at OSU? in May. As we move on to the all-important implementation A. I did. I got my master’s degree in plant breeding in phase, there will be numerous changes in how we do Wisconsin, and then I moved here to pursue my Ph.D. business here in the Institute. For instance, future Research My master’s degree was involved with traditional Newsletters will be published online only, to allow for genetics and plant breeding, and I wanted to come greater flexibility in content, linking to other articles and to OSU to study genetics at a population level. I was web-based resources, and to save expenses for printing and working with a rather obscure plant called Cuphea, mailing, which are considerable for over 14,000 copies. which was being developed for its unique spectrum of Therefore, if we do not have your email address and you seed oils. would like to continue to get our Newsletter, please send Q. How did you become involved in the Department an email to [email protected]. If you do not have access of Fisheries and Wildlife? to email and would like to continue to receive a hard copy A. When I was here as a Ph.D. student, I was diagnosed of the Newsletter, please use the enclosed card to let us with a rare genetic enzyme deficiency that causes a know. We’ll be happy to send you a copy by regular mail. metabolic muscular dystrophy. I was preparing for a As part of the strategic plan, we first developed a new career as a Mendelian geneticist doing traditional crop vision and mission for the Institute. Our vision is breeding that would have placed me out in the field, “Discovering how to live longer and feel better,” which but that was not going to be compatible with my many of you will recognize from the title of Linus Pauling’s condition. Although my underlying interest was in best-selling book touting the many health benefits of genetics, I really wanted to change my research focus vitamin C and other dietary supplements as part of a to work on metabolism, which would be compatible healthy diet and lifestyle. Our vision thus links back with the constraints of muscular dystrophy. That led to our founder and his ground-breaking concept of me to Fisheries and Wildlife, where I could establish orthomolecular medicine—the right molecule at the right my ability to work with animals. concentration to achieve optimal health and prevent Q. How did that lead to you working in disease—and at the same time looks ahead to what we are environmental and molecular toxicology? trying to achieve through our work, as explained in our A. I was aware of Dr. Williams’ work—who’s now an new mission statement: LPI Principal Investigator—and he had an opening for The mission of the Linus Pauling Institute is to promote someone to work on the metabolism by enzymes of optimal health through cutting-edge research and trusted both endogenous and exogenous compounds, including public outreach. To accomplish this, we will: pharmaceutical drugs and pesticides. continued on page 2 continued on page 2 Continued from cover — From the Director • Discover basic mechanisms underlying the biology academic institutions around the country, LPI has of aging and the causes of metabolic and age-related experienced a steady decline in federal research funding diseases over the past five years. While we will continue to pursue • Develop effective approaches to slow aging and grants from the National Institutes of Health, it will be postpone metabolic and age-related diseases through imperative for LPI to aggressively diversify and increase diet, micronutrients, and phytochemicals funding from other sources. We will have to explore business opportunities, pursue grants from private • Advance the principles of healthy living and healthy industry, and increase philanthropic support to sustain aging in the public arena, thereby empowering people our current work and realize the many new initiatives of our strategic plan. everywhere to add years of health and vitality to their lives The third goal is to communicate the LPI Advancing healthspan, not just message and raise LPI’s visibility. To this end, we will develop and implement a comprehensive lifespan, is our passion. “Discovering communications and marketing plan that will The overarching theme emerging from advance knowledge, understanding, and our strategic plan is for LPI to create, how to live support of LPI, especially among our donors, communicate, and implement new the general public, health professionals, and knowledge that will advance human longer and the media. We will also realize the full healthspan. Health is defined here not potential of the Micronutrient Information just as the absence of disease but as Center (lpi.oregonstate.edu/infocenter)—the optimal health, vitality, and resiliency into feel better” Institute’s “public face”—our comprehensive, advanced old age, free of disability and online database for scientifically accurate the deficits of daily living. The focus is on information on the roles of micronutrients and other quality of life—healthspan, “feeling better”—and on dietary factors in health and disease. closing the widening gap between lifespan and health- Finally, we will help improve public health through span in the US population and around the world. community engagement. We will support and expand The strategic plan identifies four major goals for the the efforts of LPI’s Healthy Youth Program to empower Institute. The first is to establish LPI’s leadership role youth and their families to achieve lifelong health and in advancing human healthspan through cutting-edge wellness. An important initiative will be to validate and research. This goal will be pursued through our research disseminate the high-quality outreach programs programs in healthy aging, cancer prevention and developed by the Healthy Youth Program so that they intervention, and cardiometabolic disease prevention, can be duplicated in communities around the country. supported by cross-cutting facilities offering state-of- the-art tools and technologies. One of these core You will hear a lot more about all the exciting new laboratories will develop unique screening models to initiatives going on here at LPI over the years to come. identify dietary factors and other novel compounds In the meantime, enjoy reading this Newsletter, and as that advance healthspan. always, feel free to contact us with any questions you The second goal is to diversify and increase funding may have about our work. Here’s to your good health for LPI research and outreach. Like so many other and a great spring and summer! LPI Continued from cover — Metabolizing Drugs and Toxins found where you are first exposed to a drug or a foreign chemical—the skin, lungs, liver, kidneys, and Q. When did you become a research assistant intestine. All of these organs contain flavin-containing professor in LPI? monooxygenases. A. In 2007. Q.What do FMOs do in the body? Q. You’ve been interested in a group of enzymes, the flavin-containing monooxygenases, or FMOs, for A. FMOs are similar to another family of enzymes called a long time. What do these enzymes do, and the cytochromes P450s. They are located in similar how many of them are there? places in the cell and have similar functions— metabolizing foreign substances like drugs and toxins. A. There are five different forms of flavin-containing FMOs and cytochrome P450s add an oxygen atom to monooxygenases with activity in humans. They are these molecules that makes the resulting metabolite more readily excreted from the body. 2 Spring/Summer 2014 Q. What stimulated your interest in FMOs? There is a developmental switch from FMO1 activity A. I wanted to work on enzymes that were important in in the fetal liver to FMO3 activity in the adult liver. metabolism. FMO1 declines very quickly—within three days—after birth. FMO3 is detectable by one to two years after birth Q. Are there ethnic or gender differences in the and approaches adult levels during the teenage years. activity of FMOs? Q. Are FMOs affected by diet? A. There are five different families of FMOs in humans, A. Yes, they can be. There have been a couple of studies and much of the work that I’ve done has been with where people were given about 300 grams (10.6 FMO form 2. This form is primarily located in the ounces) a day of Brussels sprouts to eat, and that lungs of humans and most other mammals. There is a depressed FMO3 activity in the liver. major mutation in this particular enzyme in people of African or Hispanic descent. Everyone else who has Q. Does that have to do with the indole-3-carbinol been tested so far has a version of the FMO2 that is in the Brussels sprouts? nonfunctional. Other FMOs also have different A. Yes, that is what we think, since indole-3-carbinol versions, called polymorphisms, but none are as wide- reduces FMO activity in animal studies.
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