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2020 Annual Report

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This is the 2020 Annual Report for Van Andel Institute.

Research highlights VAI

Research highlights VAI plans an ambitious path forward In the fall of 2020, Van Andel Institute finished outlining its new strategic vision for the next five years. This plan, called Research 4.0, lays out a bold path for the future of VAI’s research and builds on the strong foundations and success of the past — all made possible in part thanks to our donors and their steadfast dedication to our mission. Importantly, the plan affirms our focus on basic research discovery in epigenetics, neurodegenerative science, cell biology, structural biology and metabolism. It also renews our commitment to cancer and Parkinson’s through the establishment of two new Focal Centers — the VAI Cancer Center and the VAI Parkinson’s Disease Center — which serve as hubs for translating groundbreaking discoveries into clinical trials. In addition, Research 4.0 kick-started an ambitious campaign to recruit new scientists to VAI in order to grow our scientific capacity and broaden our impact. Understanding how brain cells maintain balance to keep us healthy Imagine standing on the moon and having eyes so powerful that you can clearly watch a tennis match on Earth. Now imagine that same optical power packed into a high-tech microscope, and you have cryo-EM — a groundbreaking technology that helps scientists study the smallest components of life in exquisite detail. Using the Institute’s state-of-the-art cryo-EM, VAI scientists Dr. Wei Lü and Dr. Juan Du, in collaboration with Dr. Zhaozhu Qiu of Johns Hopkins University, captured highresolution images that help explain how cells sense and respond to their environment. The images depict molecular “gates” that open and close, letting chemical messages in and out while also helping maintain pH balance within brain cells — a critical function that keeps cells alive and helps prevent stroke and other brain injuries. 5 5 Research reported in this publication was supported by Van Andel Institute; McKnight Scholar Awards in Neuroscience (Du, Qiu), Klingenstein-Simons Scholar Awards (Du, Qiu); Sloan Research Fellowships (Du, Qiu); the National Institute of General Medical Sciences of the National Institutes of Health under award no. R35GM124824 (Qiu); the National Institute of Neurological Disorders and Stroke of the National Institutes of Health under award no. R01NS118014 (Qiu), R01NS112363 (Lü) and R01NS111031 (Du); the National Heart, Lung and Blood Institute of the National Institutes of Health under award no. R56HL144929 (Lü); a Pew Scholar in Biomedical Sciences award (Du); and the American Heart Association under award no. 20POST35120556 (Ruan) and 18PRE34060025 (Osei-Owusu). The content is solely the responsibility of the authors and does not necessarily represent the official views of the granting organizations. Releasing a molecular ‘brake’ kick-starts immune cell function The immune system’s ability to marshal specialized cells to fight off infection relies in part on tiny molecules called microRNAs, which act as a release for the “brakes” that keep cells dormant until needed, according to a study by Dr. Connie Krawczyk and collaborators. The findings reveal new insights into the nuts and bolts of immune function and add to a growing body of knowledge that could one day be leveraged to optimize vaccines or immunotherapies for a number of diseases. 6 6 Research reported in this publication was supported by the National Sciences and Engineering Research Council (NSERC) under grant nos. RGPIN/2018-06257 and RGPIN/419537-2012 (Krawczyk). Brendan Cordeiro was supported by the McGill Integrated Cancer Research Training Program, the Fonds de la Rescherche du Quebec-Santé and the Canadian Institutes of Health Research. The content is solely the responsibility of the authors and does not necessarily represent the official views of the granting organizations. First detailed images of ‘molecular machine’ provide foundation for new therapies Dr. Huilin Li and his team have revealed the first known atomic structure of a “molecular machine” responsible for installing critical signaling proteins into cellular membranes. The findings, published in Nature, shed new light on how this process works and lay the foundation for potential future therapies for diseases like cancer, Alzheimer’s and cystic fibrosis. 7 7 Research reported in this publication was supported by Van Andel Institute and the National Cancer Institute of the National Institutes of Health under award no. CA231466 (Li). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. A search for the genetic roots of Alzheimer’s disease Alzheimer’s disease is the most common cause of dementia worldwide. Now, Van Andel Institute scientists believe they can strengthen our understanding of the disease’s genetic precursors and find avenues for potential new therapies by hunting for clues in one particular group with a unique genetic makeup: the Portuguese population. In the largest and first study of its kind in the country, Dr. Rita Guerreiro will identify common and rare genetic risk variants associated by mapping and analyzing the genome of a Portuguese sample population. This data will be combined with publicly available data from non-Portuguese populations to increase the diversity and statistical power of ongoing international studies. 8 8 Research reported in this publication is supported by the National Institute on Aging of the National Institutes of Health under award no. R01AG067426 (Guerreiro). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. 10 | VAN ANDEL INSTITUTE ANNUAL REPORT 2020

“Impacting human health through groundbreaking research is at the heart of VAI’s mission. Research 4.0 sets the stage for the Institute’s future and is an important reminder of how far we’ve come, particularly as we gear up to celebrate VAI’s 25th anniversary. There are great things on the horizon and, together, we can make the world a better place.” Peter A. Jones, Ph.D., D.Sc. (hon) VAI Chief Scientific Officer RESEARCH Hubs for translating impact from lab to clinic How do research breakthroughs in the lab become tangible treatments for those facing diseases like cancer and Parkinson’s? Through clinical trials, like those supported by Van Andel Institute’s Focal Centers. Established in 2020, the VAI Cancer Center and VAI Parkinson’s Disease Center provide support and infrastructure for VAI scientists seeking to develop and implement translational cancer and Parkinson’s projects in Grand Rapids, West Michigan and beyond. In the coming years, we expect the number of projects supported by the Centers to grow, multiplying the Institute’s impact in cancer and Parkinson’s. Dietary interventions may slow onset of inflammatory and autoimmune disorders Significantly reducing dietary levels of a specific amino acid, known as methionine, could slow the onset and progression of inflammatory and autoimmune disorders such as multiple sclerosis in high-risk individuals, according to a study published in Cell Metabolism by Dr. Russell Jones and his team. Autoimmune disorders occur when the immune system mistakenly attacks and destroys healthy tissue. For example, in multiple sclerosis, the immune system targets the protective covering of nerve cells in the brain and spinal cord. The subsequent damage obstructs messages traveling to and from the brain, resulting in progressively worsening symptoms like numbness, muscle weakness, coordination and balance problems, and cognitive decline. There currently are no treatments that significantly slow or stop multiple sclerosis without greatly increasing the risk of infection or cancer. These findings provide further basis for dietary interventions as future treatments for such disorders. Cancer Center The Cancer Center supports projects and clinical trials for several different types of cancer in partnership with organizations in the U.S. and abroad. Van Andel Institute–Stand Up To Cancer Epigenetics Dream Team Finding the cancer therapies of tomorrow requires visionary thinking and innovative research today. The VAI–SU2C Epigenetics Dream Team fosters collaboration between several of the world’s most respected research and clinical organizations in an effort to quickly move promising potential therapies into clinical trials. Research by the numbers 13 Trials launched 1 Trial in development 500+ Patients Parkinson’s Disease Center The Parkinson’s Disease Center supports projects and clinical trials that investigate potential therapies to slow or stop Parkinson’s progression — a feat not possible with existing treatments. International Linked Clinical Trials (iLCT) Since 2012, VAI has partnered with Cure Parkinson’s to support clinical trials of medications developed to treat other diseases that also show potential for impeding Parkinson’s progression. Research by the numbers 15 Trials launched 10 Trials in development 850+ Patients VAN ANDEL INSTITUTE ANNUAL REPORT 2020 | 11

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