2022 Annual Report

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Department of Epigenetics Scientists in VAI’s Department of Epigenetics seek to understand how epigenetic changes may either protect us from or predispose us to complex diseases such as cancer, Parkinson’s and metabolic disorders. They do so by: Building on the basics: From uncovering the underpinnings of disease to understanding the mechanisms that propel the spread of diseases like cancer, VAI scientists are dedicated to revealing the molecular machinery that underlies a variety of complex disorders. Translating discovery: Institute scientists are committed to putting laboratory discoveries to work in the real world by helping translate them into actionable new treatments that can better combat disease and save lives. Moving new therapies into the clinic: VAI works closely with leading medical organizations in the U.S. and abroad to take new therapies into the doctor’s office through clinical trials, which are vital for ensuring that new treatments are safe and effective. The Institute is home to the Van Andel Institute–Stand Up To Cancer (VAI–SU2C) Epigenetics Dream Team, a multiinstitutional, collaborative effort that brings together several of the world’s most respected research and clinical organizations to translate scientific discoveries into new standards of patient care. The goal is simple — get new and more effective cancer therapies to patients faster. For more information on our clinical collaborations, please see page 16. <strong>2022</strong> HIGHLIGHTS New cellular ‘clock’ offers fresh way to measure cellular age Cellular aging is a major risk factor for many chronic diseases, but accurately measuring it is difficult. Now, VAI scientists have developed a new method for pinpointing cellular age that evaluates the number of times a cell has divided rather than relying on chronological time. The more cells replicate, the more likely they will accumulate errors over time that contribute to diseases such as cancer. The findings, published in Nature Communications, are a vital step toward realworld applications for assessing disease risk and guiding treatment decisions in the doctor’s office. The research was led by Dr. Jamie Endicott, a recent graduate of Van Andel Institute Granduate School who worked in the lab of Dr. Peter W. Laird. Laird and Dr. Hui Shen are the corresponding authors of the study. 1 VAI, The Scientist launch podcast mini-series on health and the environment How do our environment and diet set the stage for future health? That’s one of the big questions VAI and The Scientist tackled in the podcast mini-series Exposed: Environmental Echoes in Health, part of The Scientist’s Lab Talk podcast series. The three-episode series featured VAI scientists Dr. Nick Burton, Dr. Yvonne Fondufe-Mittendorf and Dr. Heidi Lempradl, who explored how the factors to which we are exposed in our environment can impact our health and the health of future generations. All episodes of Exposed: Environmental Echoes in Health are available at The Scientist and on all major podcast platforms. The podcast accompanies a Q&A with VAI’s Dr. J. Andrew Pospisilik, who explores the long-lasting impacts of environmental exposures. Data Insights grant fuels computing projects at VAI, GVSU A collaboration between VAI’s Dr. Tim Triche, Jr. and Grand Valley State University’s Dr. Zach DeBruine to make data more accessible to researchers worldwide received support through a $200,000 Data Insights grant from the Chan Zuckerberg Initiative. The project addresses a central problem in modern, data-intensive biomedical research: how to efficiently store and analyze the massive data output from today’s technologies in a way that allows researchers and citizen-scientists to unlock insights within. For example, scientists can now catalog the differences between individual cells in extreme detail, illuminating variations that may contribute to cancer, Parkinson’s and many other diseases. But these answers are buried in vast swathes of data that must be analyzed and stored, a task that can be challenging even for highpowered computers. DeBruine is a former postdoctoral fellow in Triche’s lab who earned his doctorate from Van Andel Institute Graduate School. As part of his Ph.D. dissertation, DeBruine developed an elegant solution that repackages data files that are too big to run on a single computer into a compressed form that requires 1/10th the computing space without losing data or performance. 8
Scientists redefine obesity with discovery of two distinct subtypes A team led by VAI scientist Dr. J. Andrew Pospisilik has identified two distinct types of obesity with physiological and molecular differences that may have lifelong consequences for health, disease and response to medication. The findings, published in the journal Nature Metabolism, offer a more nuanced understanding of obesity than current definitions and may one day inform more precise ways to diagnose and treat obesity and associated metabolic disorders. The study also revealed new details about the role of epigenetics and chance in health and provides insights into the link between insulin and obesity. 2 Creation of new tool represents a paradigm shift in epigenetics research of model systems for human disease Epigenetics plays a role in virtually every aspect of health and disease, but studying exactly how and why epigenetic changes affect us has been a challenge due to a lack of appropriate tools and techniques. Now, VAI scientists and their collaborators have developed a powerful new tool that will help us better understand how epigenetics maintains health and, when things go wrong, promotes diseases such as cancer. The research was led by VAI’s Dr. Peter W. Laird and Dr. Hui Shen and will facilitate groundbreaking research around the world. 3 New technique helps scientists run circles around cancer Rampant inflammation has long been linked to cancer, but exactly how it pushes healthy cells to transform into malignant ones has remained a mystery. Now, VAI scientists have found one culprit behind this connection: oxidative stress, a process that disrupts the genetic code by damaging DNA. The findings, published in Science Advances, provide crucial new insights into the roles of inflammation and oxidative stress in certain cancers and offers new opportunities for potential prevention strategies. This work was made possible using a new technique called circle damage sequencing developed by the lab of VAI’s Dr. Gerd Pfeifer. In 2021, Pfeifer’s lab also used circle damage sequencing to determine that the mutations that give rise to melanoma result from a chemical conversion in DNA damaged by sunlight — not just a DNA copying error as previously believed. 4 Dr. Yvonne Fondufe-Mittendorf joins VAI Epigenetics expert Dr. Yvonne Fondufe-Mittendorf joined VAI’s growing faculty as a professor in January <strong>2022</strong>, a move that expanded the Institute’s research into the relationship between environmental exposures and cancer. Fondufe-Mittendorf studies the relationship between environmental factors, such as arsenic in drinking water, and cancer risk. Her research has revealed how low-dose arsenic exposure transforms healthy cells into malignant ones — revelations that have significant public health implications. Funding Acknowledgements Research reported in this publication was supported by: 1 Van Andel Institute and the National Institute on Aging of the National Institutes of Health under award no. R01AG066764 (Laird and Shen). Approximately 50% of the funding for this study came from federal sources; approximately 50% came from nonfederal sources. 2 Van Andel Institute; Max Planck Gesellschaft; the European Union’s Horizon 2020 Research and Innovation Program under Marie Skłodowska-Curie grant agreement no. 675610; the Novo Nordisk Foundation and the European Foundation for the Study of Diabetes; the Danish Council for Independent Research; the National Human Genome Research Institute of the National Institutes of Health under award no. R21HG011964 (Pospisilik); and the NIH Common Fund, through the Office of the NIH Director (OD), and the National Human Genome Research Institute of the National Institutes of Health under award no. R01HG012444 (Pospisilik and Nadeau). Approximately 5% ($50,000) of funding for this study is from federal sources; approximately 95% ($950,000) is from non-U.S. governmental sources. 3 Van Andel Institute; Children’s Hospital of Philadelphia; and the National Cancer Institute of the National Institutes of Health under award nos. R01CA157918, R01CA212374 and R01CA234125 (Laird). Shen is supported by the National Cancer Institute of the National Institutes of Health under award no. R37CA230748. Jones is supported by the National Cancer Institute of the National Institutes of Health under award no. R35CA209859. 4 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. CA228089 (Pfeifer). 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 funders. RESEARCH 727 9
Page 1 and 2: 2022 Annual Report
Page 3 and 4: Table of Contents 2 A letter from D
Page 5 and 6: “From all of us at Van Andel Inst
Page 8 and 9: Department of Neurodegenerative Sci
Page 12 and 13: Department of Cell Biology Our heal
Page 14 and 15: Department of Structural Biology Sc
Page 16 and 17: Department of Metabolism & Nutritio
Page 18 and 19: Translating impact from lab to clin
Page 20 and 21: Core Technologies & Services Van An
Page 22 and 23: Van Andel Institute Principal Inves
Page 30 and 31: A modern approach to graduate educa
Page 32 and 33: A modern approach to graduate educa
Page 34: Van Andel Institute for Education W
Page 37 and 38: K-12 EDUCATION 35
Page 39 and 40: K-12 EDUCATION 37
Page 42 and 43: Carol Van Andel Angel of Excellence
Page 44 and 45: Design & Discovery Merging the insp
Page 46 and 47: Around the World Hosted by VAI’s
Page 48 and 49: Couture for a Cure Michigan’s pre
Page 50 and 51: Hope on the Hill & The Chocolate Fa
Page 52 and 53: Signature special event sponsors We
Page 54 and 55: A decade of support: Inside Jeffery
Page 56 and 57: Positivity & perseverance: Richard
Page 58 and 59: From Purple Community to JBoard Amb
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Running for family & research Nearl
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Philanthropy Circle of Hope Anonymo
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Van Andel Institute Board Members V
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Van Andel Institute Board of Govern
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333 Bostwick Ave. NE, Grand Rapids,
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2022 Annual Report

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