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2020 Fall/Winter Highlights of Hope

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RESEARCH VAI scientists

RESEARCH VAI scientists continue to achieve breakthroughs during pandemic Despite the challenges presented by the COVID-19 pandemic, Van Andel Institute scientists continue to make groundbreaking discoveries, collaborate with colleagues around the world and earn recognition for their efforts. Here is a snapshot of some recent advances and achievements. VAI welcomes Parkinson’s expert to its team This summer, VAI welcomed Dr. Michael Henderson to its growing team of scientists. An expert in Parkinson’s disease and dementia with Lewy bodies, Dr. Henderson investigates the role of abnormal proteins in disease onset and progression, with the goal of developing new, life-changing therapies. He has made landmark contributions to the understanding of Parkinson’s and neurodegeneration, such as showing that alpha-synuclein proteins take advantage of the brain’s own structure to spread and that an enzyme called glucocerebrosidase (GBA) plays an important role in propelling alpha-synuclein’s propagation. Scientists recognized for collaborative effort to take on cancer The American Association for Cancer Research awarded 2020 AACR Team Science Awards to VAI Professor Dr. Peter W. Laird, Director’s Scholar Dr. Stephen B. Baylin and Associate Professor Dr. Hui Shen for their pivotal roles in the establishment and success of The Cancer Genome Atlas (TCGA), a landmark National Institutes of Health-led project that revolutionized our understanding of cancer and that is hailed as an exemplar of scientific collaboration. The awards recognize more than 100 individuals who were central to TCGA from its inception through today. Baylin holds a primary appointment at Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University. Parkinson’s-related gene linked to cellular recycling Growing evidence suggests Parkinson’s disease may result, at least in part, from breakdowns in cellular recycling systems, which lead to a build-up of toxic proteins that eventually kill vital brain cells. Now, Dr. Darren Moore and colleagues have found that LRRK2, a gene linked to Parkinson’s, works with other molecular complexes to support these critical systems. As such, abnormal changes to LRRK2 disrupt normal cellular function and could contribute to disease onset. The discovery opens doors for possibly targeting LRRK2 as a new way to treat Parkinson’s. A new ‘blueprint’ reveals inner workings of drug target A team led by Dr. Wei Lü and Dr. Juan Du has for the first time described the near-atomic level structure of the pannexin1 channel. The molecular pathway plays critical roles in human development, blood pressure regulation, inflammation and cell death. Their findings, published in Nature, serve as a “blueprint” for developing new medications for a host of conditions, such as cancer and heart disease. 2 | VAN ANDEL INSTITUTE HIGHLIGHTS OF HOPE

Newly discovered potential biomarker could ‘flag’ tumors sensitive to metabolic therapy A recently identified potential biomarker could help scientists pinpoint which cancers are vulnerable to treatment with biguanides, a common class of medications used to control blood sugar in Type 2 diabetes. Biguanides have long been of interest to cancer researchers because of their ability to target cellular metabolism, which fuels the growth and spread of malignant cells. The discovery, published by Dr. Russell Jones and collaborators, may give scientists a way to objectively determine which types of cancer are sensitive to biguanide treatment and illuminates how and why some patients may respond better to biguanides than other patients. First detailed images of ‘molecular machine’ provide foundation for new therapies Dr. Huilin Li and his team have revealed the first known atomic structure of a “molecular machine” responsible for installing critical signaling proteins into cellular membranes. The findings, published in Nature, shed new light on how this process works and lay the foundation for potential future therapies for diseases like cancer, Alzheimer’s and cystic fibrosis. Releasing a molecular ‘brake’ kick-starts immune cell function The immune system’s ability to marshal specialized cells to fight off infection relies in part on tiny molecules called microRNAs, which act as a release for the “brakes” that keep cells dormant until needed, according to a study by Dr. Connie Krawczyk and collaborators. The findings reveal new insights into the nuts and bolts of immune function and add to a growing body of knowledge that could one day be leveraged to optimize vaccines or immunotherapies for a number of diseases. Early career scientists adapt to working remotely by taking science virtual For many scientists, working from home was a temporary transition away from hands-on research in the lab to more virtual projects like data analysis. As a way to ensure continued scientific discussion and collaboration, VAI postdoctoral fellows Dr. Michaela Johnson and Dr. Liza Bergkvist teamed up with The Cure Parkinson’s Trust and World Parkinson Coalition to establish the Parkinson Postdoc Program seminar series, or 3P Seminars. Launched in April, the interactive, virtual seminars give early career researchers who study neurodegenerative diseases a way to keep the intellectual part of research alive by connecting with others in their field and providing space for them to practice presenting their work. VAN ANDEL INSTITUTE HIGHLIGHTS OF HOPE | 3

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