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2019 Spring/Summer Highlights of Hope

RESEARCH UNCOVERING HOW

RESEARCH UNCOVERING HOW THE BODY’S FUELING SYSTEM AFFECTS HUMAN HEALTH It takes a lot of energy to keep the human body up and running. But where does this energy come from? And how does it affect every aspect of our lives? The answer is metabolism — a set of constantly occurring chemical reactions that provides the fuel for day-to-day life, from keeping the heart beating to aiding in digestion. Although metabolism is a central part of human health and well-being, there’s still much that we don’t know about how it works and how it contributes to a host of health problems. That’s why, last fall, Van Andel Research Institute (VARI) established the most comprehensive metabolism research program of its kind, aimed at developing scientifically driven strategies for improving health and for treating diseases like cancer, Parkinson’s and diabetes. This collaborative effort comprises six laboratories, four of which are new, to investigate the full spectrum of metabolism, from dietary influences to how cancer cells hijack metabolic processes. “Metabolism is involved in each and every process in the body, from big, system-level things like our immune defenses down to smallerscale things like the life cycles of individual cells,” said Dr. Russell Jones, the program’s leader, who joined the Institute from McGill University in 2018. “We have so much to learn. It is our hope that we can leverage what we find to prevent disease and to better treat it when it does occur.” To start, the program will focus on several areas, including: Understanding the role of nutrition in one generation and beyond When most people hear the word “metabolism,” food is the first thing that comes to mind. While it is a major player in metabolism, it’s important to remember that food consumption is part of a bigger story. During digestion, the body breaks food down into its most basic components — sugars, amino acids, vitamins and minerals. Some of these nutrients will be used right away to fuel everyday function, while others will be stored for later use. VARI scientists are investigating how nutrition impacts health and risk for disease and is exploring if these effects can be passed down through the generations. Better targeting and treating cancer Cancer cells have a voracious appetite for energy, which propels their invasive spread throughout the body. But this strength may also be a weakness — the by-products produced by their out-ofcontrol metabolisms may help locate and identify cancers early on, allowing for treatment of some cancers much sooner than currently possible with existing detection methods. For example, certain cancers, such as those in the pancreas, produce special carbohydrates called glycans that one day could be used for earlier and more definitive diagnoses. Think of them like molecular fingerprints that scientists can use to differentiate a sick cell from a healthy cell. But that’s not all. VARI scientists also are searching for ways to starve cancer cells of energy and, in doing so, could uncover new, more effective ways to treat the disease. Drilling down on the causes of Parkinson’s disease There’s still much we don’t know about the root causes of Parkinson’s, a neurodegenerative disorder that affects 7 to 10 million people worldwide. Today, new discoveries are pulling back the curtain on some of the metabolic mechanisms that cause cells in the brain to die off, leading to the disease’s hallmark movementrelated symptoms. Growing evidence shows that problems with cellular powerplants, known as mitochondria, may cause cells to dysfunction, allowing toxic proteins and other debris to build up, eventually clogging and killing the cells. By figuring out how and why this happens, VARI scientists hope to develop new ways to interfere with this devastating process and stop Parkinson’s in its tracks. Bringing it all together Metabolism isn’t just one thing — it’s a constellation of systems and processes working in elaborate concert to power life. The Institute’s new program reflects this connectivity and collaborative spirit, and aims to translate the promise of discovery into everyday practice — changing the way diseases like cancer and Parkinson’s are treated and improving the lives of people around the world. Learn more about the Institute’s metabolism research at vari.vai.org. 2 | VAN ANDEL INSTITUTE HIGHLIGHTS OF HOPE

Metabolic and Nutritional Programming Team RUSSELL JONES, PH.D., PROGRAM LEAD BRIAN HAAB, PH.D. CONNIE KRAWCZYK, PH.D. ADELHEID LEMPRADL, PH.D. J. ANDREW POSPISILIK, PH.D. NING WU, PH.D. VAN ANDEL INSTITUTE HIGHLIGHTS OF HOPE | 3

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