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2020 Spring/Summer Highlights of Hope

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RESEARCH 10 RESEARCH

RESEARCH 10 RESEARCH TRENDS WE’RE EXCITED TO WATCH IN THE NEXT DECADE With a new decade comes a new world of possibility, and innovation waiting to be unleashed in labs at Van Andel Institute and across the globe. As we take our first steps into the 2020s, here are 10 promising research trends to keep an eye on now and in the coming years. Our understanding of Parkinson’s disease will continue to evolve, spurring new research and breakthroughs Parkinson’s disease has long been considered a movement-related disorder that originates in the brain. Recent research, however, suggests that Parkinson’s disease might represent a group of closely related disorders. While they share key clinical features, they may have roots in different anatomical locations, such as the gut and nose. Even if the anatomical starting points differ, there is evidence that cell metabolism, inflammation and poor handling of certain proteins are common features. In the coming years, these insights could lead to the development of new therapies to slow or stop its progression. Breakthroughs in common diseases like Parkinson’s, dementia with Lewy bodies and Alzheimer’s might help us better understand rare disorders It’s become increasingly clear that an improved understanding of one disease may provide new insights into another. For rare and understudied diseases like multiple system atrophy, this provides a particularly important opportunity to gain the insight required to develop new diagnostics and treatments. Inflammation will increasingly be linked to disease — and give rise to new treatments Inflammation is a normal part of the immune system, responsible for marshalling resources to the site of a wound, infection or disease (like cancer) to help the body fight back. When inflammation remains longer than needed, it can cause or contribute to a host of health problems. Researchers are hard at work sorting out exactly how and why this happens, which could be the findings that serve as the foundation for new therapies for cancer, neurodegenerative diseases, depression and many others. Understanding how the body processes, uses and stores energy will be critically important Metabolism powers every aspect of the human body, from keeping the immune system running to ensuring our hearts have enough energy to beat. We’ve known for some time that metabolic dysfunction plays a central role in diseases like diabetes and even in cancer, thanks to malignant cells’ voracious appetites for energy. But new breakthroughs also have linked issues with metabolism to neurodegenerative diseases like Parkinson’s and Alzheimer’s, among others. As we better understand our bodies’ incredibly complex web of metabolic processes, it’s likely that we will continue to find metabolism at the center of many disorders — and many future treatments. Cancer treatment will harness combinations of medications designed to give cancer a one-two punch We now know that cancer comprises more than 100 different diseases, each with its own litany of subtypes (for example, breast cancers can be defined based on the presence or absence of certain molecular receptors). This expansive diversity means that there is likely no silver bullet cure. Instead, we can expect to see more combination therapies that utilize multiple medications whose effects complement or enhance each other’s ability to fight cancers. A prime example is pairing an immunotherapy drug, which bolsters the body’s natural defenses against cancer, with an epigenetic drug that makes cancer cells more recognizable, more susceptible to immune attack, and is thought to reinvigorate exhausted immune cells and get them back in the fight. We will better understand how the health and diet of one generation can affect the next Can a parent’s diet, experiences and lifestyle impact their children? Or subsequent generations? Mounting evidence suggests that nutrition does indeed have a ripple effect across generations, even altering individuals’ predisposition to disease. Efforts are underway to better understand how nutrition and other environmental factors reprogram the genome and epigenome, and how this information traverses generations. The goal: developing ways to prevent and treat diseases including diabetes, cancer, and Parkinson’s, and to protect our children from the unwanted consequences of our own lifestyles. We will see the translation of structural findings into actionable therapies Structural biology seeks to determine the shape and architecture of life’s smallest building blocks, such as proteins. These efforts are vitally important, helping us understand in intricate chemical detail how the body works and laying the earliest foundations for new medications. In the past five years, there has been a boom in structural research, based on technological advances in cryoelectron microscopy (cryo-EM), a technique that helps scientists view molecules down to the atomic level. In the next decade, we will continue to build on these foundational discoveries, which could give rise to new treatments. 2 | VAN ANDEL INSTITUTE HIGHLIGHTS OF HOPE

We’ll learn more about microenvironments and microbiomes and their role in cancer and other diseases In many ways, the future will be “micro.” Our technology is miniaturizing; we are able to study the tiniest components of life in ways never before possible and scientists are increasingly understanding the importance and diversity of microenvironments, the mini ecosystems that exist throughout the body. In cancer, the microenvironment is the area immediately surrounding a tumor, which can comprise blood vessels, immune cells and structural cells, among others. These areas offer windows into how specific cancers grow and proliferate, and may even offer new solutions for stopping them. We’re also learning more about the role of microbiomes, the host of microscopic organisms such as bacteria that inhabit specific areas of the body like the gut. For example, researchers who are sleuthing out the links between the gut and Parkinson’s disease are taking a look at the gut microbiome as a possible factor in disease onset. Technology will spur even more innovation Editing genes using CRISPR. Determining molecular structures with high-powered cryo-EM. Decoding the genome through nextgeneration sequencing. The advent of these powerful technological tools, paired with increasingly robust computational capabilities, have revolutionized how we study health and disease, and already have contributed to critical biomedical breakthroughs. With technology continually advancing, we can only expect the innovation to continue in years to come. Big Data will continue to yield new insights Big Data refers to the massive amounts of information generated by certain types of research, such as genomics. With technology improving every day, the amount of data being churned out will only continue to balloon, presenting opportunities and challenges to scientists working to get to the root of disease. By closely analyzing large datasets (a monumental task itself), scientists can look for patterns linked to disease. A prime example is The Cancer Genome Atlas, a National Institutes of Health-led effort that molecularly mapped 33 different types of cancer. These highly detailed and vast datasets helped identify important variations in cancer types and subtypes that may form the foundation of new targeted therapies. To read more about Van Andel Institute’s research in these areas, visit vai.org/10-trends-2020s. VAN ANDEL INSTITUTE HIGHLIGHTS OF HOPE | 3