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2022 Spring/Summer Highlights of Hope

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This is the 2022 Spring/Summer edition of Van Andel Institute's Highlights of Hope donor publication.

RESEARCH VAI scientists

RESEARCH VAI scientists recognized as top of their fields It’s no secret that VAI scientists are among the world’s best. This year, five of our investigators were honored with inclusion on the Clarivate Highly Cited Researchers List, a distinction marking them as leaders in their fields. The annual list identifies scientists from around the world who demonstrate significant influence in their area of study through the publication of multiple highly cited papers during the last decade. Citations, or references, to a scientist’s published work by other researchers is universally considered to be a measure of influence and impact in the scientific community. Only about 1 in 1,000 scientists in the world make this elite list, according to Clarivate. Peter A. Jones, Ph.D., D.Sc. (hon) Chief Scientific Officer Director, VAI Cancer Center Patrik Brundin, M.D., Ph.D. Deputy Chief Scientific Officer Director, VAI Parkinson’s Disease Center Read more online at vaihrc21 Russell Jones, Ph.D. Chair, Department of Metabolism and Nutritional Programming Peter Laird, Ph.D. Professor, Department of Epigenetics X. Edward Zhou, Ph.D. Senior Research Scientist, Li Lab Department of Structural Biology 8 | VAN ANDEL INSTITUTE HIGHLIGHTS OF HOPE

Research highlights Looking for the latest from VAI’s scientists? Here’s a snapshot of advances from the Institute’s labs. Understanding gut inflammation may hold clues to mitigating Parkinson’s onset Chronic inflammation in the gut may propel processes in the body that give rise to Parkinson’s disease, according to a study by Dr. Patrik Brundin’s lab at VAI and colleagues at Roche. The findings add to a growing list that links the gut and the immune system to Parkinson’s, and track with several large-scale studies that show an association between Parkinson’s and inflammatory bowel diseases, such as ulcerative colitis and Crohn’s disease. 1 Read more at ‘Roadmaps’ of the brain reveal regions vulnerable to Alzheimer’s disease Much like a supply truck crossing the countryside, the misfolded proteins that damage neurons in Alzheimer’s disease travel the “roads” of the brain, sometimes stopping or even re-routing to avoid roadblocks, reports a study by VAI’s Dr. Michael Henderson and collaborators at University of Pennsylvania. Understanding how and why this happens could clear the way for the development of new therapies to slow or stop disease progression. 2 Read more at ‘Tasty’ protein may lead to new ways to treat metabolic and immune diseases The same taste-sensing molecule that helps you enjoy a meal from your favorite restaurant may one day lead to improved ways to treat diabetes and other metabolic and immune diseases. TRPM5 is a specialized protein concentrated in the taste buds, where it helps relay messages to and from cells. It has long been of interest to researchers due to its roles in taste perception and blood sugar regulation. VAI scientists Dr. Wei Lü and Dr. Juan Du have published the firstever high-resolution images of TRPM5, which reveal two areas that may serve as targets for new medications for diseases like diabetes. These structures also may aid in the development of low-calorie alternative sweeteners that mimic sugar. 3 Read more at Study sheds light on how DNA mutates in melanoma, a deadly skin cancer The mutations that give rise to melanoma result from a chemical change in DNA fueled by sunlight — not just a DNA copying error as previously believed, reports a study by VAI’s Dr. Gerd Pfeifer. The findings upend long-held beliefs about the mechanisms underlying the disease, reinforce the importance of prevention efforts and offer a path forward for investigating the origins of other cancer types. 4 Read more at An overactive sweet tooth may spell trouble for our cellular powerplants Although we’ve long known that eating too much sugar can contribute to Type 2 diabetes and other disorders, the exact way this overconsumption sets the stage for metabolic diseases on a cellular level has remained elusive. But now, a study led by VAI’s Dr. Ning Wu has shown that surplus sugar may cause our cellular powerplants — called mitochondria — to become less efficient, reducing their energy output. The findings highlight the cellular implications of excessive sugar consumption and provide an important new model to study the initial metabolic events that may contribute to diabetes development. 5 Read more at Funding Acknowledgements Research reported in this publication was funded by: 1 Van Andel Institute and Roche. Early work on this project was supported in part by the European Research Council. 2 Michael J. Fox Foundation for Parkinson’s Research award no. 16879 (Henderson); the National Institute on Aging of the National Institutes of Health under awards T32AG000255 (Lee), P30AG10124 (Trojanowski) and U19AG062418 (Trojanowski);the National Institute of Neurological Disorders and Stroke of the National Institutes of Health under award nos. P50NS053488 (Trojanowski) and R01NS099348 (Bassett); the National Institute of Mental Health of the National Institutes of Health under award no. F30 MH118871-01 (Cornblath); and the National Science Foundation under award nos. PHY1554488 (Bassett) and BCS1631550 (to Bassett). Bassett also acknowledges support from the John D. and Catherine T. MacArthur Foundation, the ISI Foundation, the Alfred P. Sloan Foundation, and the Paul G. Allen Foundation. 3 Van Andel Institute; the National Heart, Lung, and Blood Institute of the National Institutes of Health under award no. R56HL144929 (Lü) and R01HL153219 (Lü); a McKnight Scholar Award (Du); a Klingenstein-Simons Scholar Award (Du); a Sloan Research Fellowship in neuroscience (Du); and a Pew Scholars in Biomedical Research Award from the Pew Charitable Trusts (Du). 4 Van Andel Institute and the National Cancer Institute of the National Institutes of Health under award no. R21CA228089 (Pfeifer). 5 Van Andel Institute; the National Institute of General Medical Sciences of the National Institutes of Health under award no. R01GM120129 (Wu); and the National Institute on Aging of the National Institutes of Health under award no. RF1AH061872 (Han). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health or other granting organizations. VAN ANDEL INSTITUTE HIGHLIGHTS OF HOPE | 9

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