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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 Structural Biology Imagine standing on the moon and having eyes so powerful that you can clearly watch a tennis match on Earth. Now imagine that same visual power packed into a high-tech microscope, and you have cryo-EM — a groundbreaking technology that allows scientists to study the smallest components of life in exquisite detail. Determining the shape of these critical molecules is vital for understanding their function in health and disease. Scientists in Van Andel Institute’s Department of Structural Biology harness cryo-EM and other state-ofthe-art techniques to visualize molecules that may serve as treatment targets for cancer, neurological disorders, metabolic diseases, infectious diseases and more. They’re revealing groundbreaking new insights into the most fundamental aspects of biology, from parsing the ways cells sense and respond to the environment to illuminating the intricacies of DNA replication. And they’re laying the foundations for new therapies by revealing how a drug molecule disables its target protein. Huilin Li, Ph.D. Chair and Professor; Director, Cryo-EM Core Dr. Huilin Li uses cryo-electron microscopy (cryo-EM) to reveal the most basic building blocks of DNA replication and other systems vital for life. He has been at the vanguard of cryo-EM for more than 20 years, and his research has implications for some of the world’s most critical public health concerns, including tuberculosis, cancer, mental illness, and many more. Juan Du, Ph.D. Associate Professor Dr. Juan Du seeks to understand the brain’s intricate communication systems using state-of-the-art structural biology approaches, such as cryo- EM. Her work has revealed new insights into critical processes such as temperature regulation in the human body, which has implications for development of new medications for neurological disorders. Wei Lü, Ph.D. Associate Professor Dr. Wei Lü is working to unravel how brain cells communicate with each other. Using techniques such as cryo-EM, his work has contributed to the field’s understanding of molecules that play crucial roles in the development and function of the nervous system. Evan Worden, Ph.D. Assistant Professor Dr. Evan Worden leverages VAI’s powerful suite of cryo-electron microscopes to explore the complex molecular interactions that give rise to cancer. To date, his research has revealed novel insights into poorly understood regulatory elements in the genetic code and illuminated how aberrations in these processes can transform healthy cells into malignant ones. 22

RESEARCH Department of Metabolism and Nutritional Programming For the human body to function properly, it must have the right amount of energy and resources in the right place at the right time. Every aspect of life is fueled by metabolism, a constant cascade of chemical reactions that ensure we have the energy to survive and thrive. But sometimes things go wrong, depriving our cells of the energy and resources required for healthy function. When energy production or distribution breaks down, the results can be catastrophic — diseases such as cancer, Parkinson’s and diabetes are all known to have varying degrees of metabolic involvement. Scientists in Van Andel Institute’s Department of Metabolism and Nutritional Programming explore the intricate mechanics of cellular metabolism and their implications for health and in disease. Using cuttingedge techniques, they are investigating metabolism’s interaction with other critical systems, such as the immune system, and revealing how environmental exposures and metabolic dysfunction contribute to diseases such as diabetes, autoimmunity, cancer and neurodegeneration. Our scientists are also parsing the ripple effect that nutrition may have through the generations, exploring how our diets could lay the epigenetic foundations for the health of our descendants. Russell Jones, Ph.D. Chair and Professor Dr. Russell Jones investigates metabolism at the cellular level to understand how it affects cell behavior and health, with a specific eye on cancer and the immune system. By revealing how cancer cells use metabolic processes to fuel their growth and spread, he hopes to develop new treatments that help patients by changing the standard of care for cancer. Connie Krawczyk, Ph.D. Associate Professor Dr. Connie Krawczyk investigates the links between metabolism, epigenetics and the immune system, with the goal of understanding how they work together to keep us healthy and, when things go wrong, to promote disease. Adelheid Lempradl, Ph.D. Assistant Professor Dr. Adelheid Lempradl is investigating how the dietary choices of parents may impact the health of their offspring in the hopes of translating her findings into new ways to prevent disease and create a healthier future. Sara Nowinski, Ph.D. Assistant Professor Dr. Sara Nowinski investigates how cells determine the amount of energy needed for everyday life and how they adjust to meet those requirements. Her research has uncovered new insights into the intricate balance between nutrient availability and cellular respiration — both critical components to maintaining health. Ning Wu, Ph.D. Assistant Professor Dr. Ning Wu investigates the interface between cellular metabolism and cellular signaling, particularly as they relate to cancer. On the most basic level, cancer is fundamentally a disease of uncontrolled cell growth, and Dr. Wu believes that understanding a tumor’s voracious energy requirements and altered signaling pathways will lead to new treatments that optimize existing combination therapies and identify novel therapeutic targets. 23

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