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2021 Annual Report

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This is the 2021 Annual Report for Van Andel Institute.

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Department of Epigenetics Scientists in Van Andel Institute’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 to 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 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 multi-institutional, collaborative effort that brings together several of the world’s most respected research and clinical organizations in an effort 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 15. 2021 HIGHLIGHTS Early study points to potential therapeutic avenue for a pair of rare pediatric diseases (Dr. Piroska Szabó) — VAI scientist Dr. Piroska Szabó and colleagues have devised a new approach for detecting and potentially heading off the effects of two rare pediatric diseases before birth. The study, performed in lab models of the diseases and published in Cell Reports, represents an important step toward much-needed early interventions for Beckwith- Wiedemann syndrome and Silver-Russell syndrome. Both diseases result in growth-related symptoms in children and often lead to additional problems later in life, such as increased cancer risk from Beckwith- Wiedemann syndrome and increased metabolic disease risk from Silver-Russell syndrome. 1 Study explores how environmental exposures before conception may impact fetal development (Dr. Peter A. Jones) — A report published in Proceedings of the National Academy of Sciences suggests older age and alcohol consumption in the year leading up to conception may epigenetically alter a specific gene during development of human eggs, or oocytes. Although the study did not determine the ultimate physical effects of this change, it provides important insights into the intricate relationship between environmental exposures, genetic regulation and human development. 2 Study reveals source of DNA mutations in melanoma (Dr. Gerd Pfeifer) — The mutations that give rise to melanoma result from a chemical conversion in DNA fueled by sunlight — not just a DNA copying error as previously believed, reports a study by Van Andel Institute scientists published in Science Advances. 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. 3 Coriell Institute for Medical Research, Van Andel Institute awarded estimated .4 million SPORE grant from National Cancer Institute (Dr. Peter A. Jones and Dr. Stephen Baylin) — The Coriell Institute for Medical Research and VAI were awarded a prestigious Specialized Programs of Research Excellence (or SPORE) grant from the National Cancer Institute (award P50CA254897). The five-year grant valued at an estimated .4 million supports nearly 20 scientists as they work to improve epigenetic therapies for cancer. The project is co-led by Coriell’s President and CEO Dr. Jean-Pierre Issa, VAI’s Chief Scientific Officer Dr. Peter A. Jones and Johns Hopkins University and VAI’s Dr. Stephen Baylin. 6

RESEARCH Van Andel Institute, Maine Medical Center Research Institute scientists earn .6 million Transformative Research Award from National Institutes of Health (Dr. J. Andrew Pospisilik) — VAI’s Dr. J. Andrew Pospisilik and Maine Medical Center Research Institute’s Dr. Joseph Nadeau earned a five-year, .6 million Transformative Research Award from the National Institutes of Health to answer a set of questions that could fundamentally transform our understanding of health and disease: If you were born multiple times under the exact same circumstances, would you turn out to be the same person each time? And if not, what implications could the differences have for your health? The answers could revolutionize our understanding of how probabilistic variation influences health before birth and throughout life — and provide insights into new strategies for combating cancer, obesity and a host of other health concerns and diseases. This groundbreaking research is made possible by a Transformative Research Award, part of the NIH Common Fund’s High-Risk, High-Reward Research Program. The award promotes cross-cutting, interdisciplinary approaches to projects that have potential to create new paradigms or challenge existing ones, according to NIH. 4 American Cancer Society grant to support Van Andel Institute research into anti-cancer medications (Dr. Scott Rothbart) — Dr. Scott Rothbart earned a four-year, 2,000 Research Scholar’s Grant from the American Cancer Society to investigate the mechanisms that power a promising class of potent anti-cancer drugs. The drugs, called EZH2 inhibitors, work by targeting an enzyme called EZH2 that has long been of interest to cancer researchers because it interacts with the proteins that support DNA. As such, EZH2 plays a major role in switching genes that regulate cell proliferation “on” or “off” — a process that can lead to cancer if it goes awry. It also helps tumors evade attack by the immune system. Because of their central role in all aspects of health and disease, proteins and the molecules that interact with them, such as EZH2, often are powerful targets for therapeutic development. Currently, several EZH2 inhibitors are undergoing clinical trials in cancer. 5 7 Funding Acknowledgements Research reported in this publication was funded by: 1 Van Andel Institute and the National Institute of General Medical Sciences of the National Institutes of Health under award no. R01GM064378 (Szabó). 2 Van Andel Institute and the National Institute of General Medical Sciences of the National Institutes of Health under award no. F32GM129987 (Carpenter). 3 Van Andel Institute and the National Cancer Institute of the National Institutes of Health under award no. R21CA228089 (Pfeifer). 4 The Office of the Director of the National Institutes of Health under award no. 1R01HG012444 (Pospisilik and Nadeau). 5 A Research Scholar Grant, RSG-21-031-01-DMC (Rothbart) from the American Cancer Society. 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.

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