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2021 Annual Report

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This is the 2021 Annual Report for Van Andel Institute.

Van Andel Institute

Van Andel Institute Principal Investigators DEPARTMENT OF EPIGENETICS (CONTINUED) Peter W. Laird, Ph.D. Professor Dr. Peter W. Laird seeks a detailed understanding of the molecular foundations of cancer, with a particular focus on identifying crucial epigenetic alterations that convert otherwise healthy cells into cancer cells. He is an international leader in this effort and has helped design some of the world’s state-of-the-art tools to aid in epigenetics research. Laird also is a principal investigator for the National Cancer Institute’s Genome Data Analysis Network and played a leadership role in The Cancer Genome Atlas, a multi-institutional effort to molecularly map cancers. Gerd Pfeifer, Ph.D. Professor Dr. Gerd Pfeifer studies how the body switches genes on and off, a biological process called methylation that, when faulty, can lead to cancer or other diseases. His studies range from the effect of tobacco smoke on genetic and epigenetic systems to the discovery of a mechanism that may help protect the brain from neurodegeneration. Scott Rothbart, Ph.D. Associate Professor Dr. Scott Rothbart studies the ways in which cells pack and unpack DNA. This elegant process twists and coils roughly 2 meters of unwound DNA into a space less than one-tenth the width of a human hair. Although this process is impressive, it is also subject to errors that can cause cancer and other disorders. Rothbart seeks new targets for drug development in this process. Hui Shen, Ph.D. Associate Professor Dr. Hui Shen develops new approaches to cancer prevention, detection and treatment by studying the interaction between genes and their control systems, called epigenetics. Her research focuses on women’s cancers, particularly ovarian cancer, and has shed new light on the underlying mechanisms of other many cancer types. Xiaobing Shi, Ph.D. Professor Dr. Xiaobing Shi investigates the mechanisms that regulate DNA and gene expression to better understand how they impact cancer development. His research has led to the discovery of several new “readers” of epigenetic marks that may serve as targets for cancer treatment. Piroska Szabó, Ph.D. Associate Professor Dr. Piroska Szabó studies the flow of epigenetic information from parents to their offspring, with a focus on how epigenetic markers are remodeled during egg and sperm production, and how these markers are rewritten after fertilization. These processes have profound implications on fertility and embryo development. Timothy J. Triche, Jr., Ph.D. Assistant Professor As a statistician and computational biologist with an interest in clonal evolution and cancers of the blood, the work of Dr. Tim Triche, Jr., focuses on wedding data-intensive molecular phenotyping to adaptive clinical trial designs in an effort to accelerate the pace of drug targeting and development in rare or refractory diseases. Hong Wen, Ph.D. Associate Professor Dr. Hong Wen investigates the molecular underpinnings of pediatric cancers, with a focus on how epigenetic dysregulation impacts gene expression and drives malignancy. Her work holds great promise for developing new, improved therapies for these devastating diseases. 18

RESEARCH Department of Neurodegenerative Science Worldwide, between 7 million to 10 million people have Parkinson’s disease, a progressive neurological condition marked by tremor, rigidity and the gradual loss of voluntary movement, along with a host of other symptoms such as loss of sense of smell, cognitive issues, constipation, trouble sleeping and pain. Additionally, more than 30 million people have Alzheimer’s disease and related dementias. Currently, there is no cure and no effective way to slow or stop disease progression in Parkinson’s and Alzheimer’s. VAI scientists aim to change that by investigating the complex factors that give rise to neurodegenerative and psychiatric disorders, from genetics and epigenetics to aging, inflammation and the structure of the brain itself — even the role of the gut and the immune system. With the exception of a small number of people whose Parkinson’s is directly linked to family genetic inheritance, most cases are sporadic, meaning they have no known cause. A growing body of evidence suggests that genetic and epigenetic predisposition coupled with environmental factors, such as exposure to certain inflammatory agents, may trigger the disease, which progresses for years or even decades before the onset of its signature movementrelated symptoms. With an aging global population, the number of people with Parkinson’s or Alzheimer’s is expected to significantly increase in the coming years, underscoring the importance and urgency of developing improved treatment strategies. By leveraging discoveries made in VAI’s labs and collaborating with researchers around the world, our scientists are working to translate breakthroughs into lifechanging new treatments. Darren Moore, Ph.D. Chair and Professor Dr. Darren Moore seeks new diagnostic and treatment approaches for Parkinson’s by investigating the inherited form of the disease, which comprises 5% to 10% of cases. He aims to translate the understanding of these genetic mutations into better treatments and new diagnostic tools for Parkinson’s, both inherited and non-inherited. Discoveries from Moore’s lab routinely elucidate the faulty molecular interactions that transform healthy, functioning neurons into diseased ones. José Brás, Ph.D. Associate Professor Dr. José Brás investigates how variations in our genes impact the onset and progression of neurodegenerative diseases such as Parkinson’s, Alzheimer’s and dementia with Lewy bodies. Using cutting-edge technologies and bioinformatic approaches, he has identified new genetic mutations that impact disease risk. Lena Brundin, M.D., Ph.D. Professor As a psychiatrist and a scientist, Dr. Lena Brundin seeks ways to diagnose and treat depression and suicidality by studying inflammation of the nervous system. Her findings may lead to earlier interventions for depressive patients and to development of a new class of antidepressants that targets the immune system. She also investigates how inflammatory mechanisms can damage nerve cells in Parkinson’s disease. Hong-yuan Chu, Ph.D. Assistant Professor Dr. Hong-yuan Chu investigates how and why dopamineproducing cells die off in Parkinson’s, a process that underlies many of the disease’s hallmark symptoms. He plans to leverage this new knowledge to develop new, more precise ways to slow or stop disease progression. Gerhard Coetzee, Ph.D. Professor Dr. Gerhard Coetzee searches the human genome for minuscule changes that contribute to the onset, progression and drug resistance of many diseases, including cancer and Parkinson’s. His team deploys genome sequencing technologies and high-powered computational arrays to tease out patterns and interactions of markers and treatment targets from among the human genome’s more than three billion DNA base pairs. 19

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