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2019 Highlights of Hope: Fall/Winter

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RESEARCH DR. JUAN DU

RESEARCH DR. JUAN DU WORKS TO SOLVE MYSTERIES OF THE BODY’S TEMPERATURE REGULATION SYSTEM The human body is an elegant machine, one whose temperature is kept in check by an intricate biological thermostat. But despite its critical role in keeping us healthy and protecting us from heat or cold-related injuries, little is known about exactly how this system works. Van Andel Institute’s Dr. Juan Du hopes to solve this problem from the ground up by determining the structures and functions of its components, namely communication hubs called ion channels that allow chemical messengers to pass into and out of cells. Her groundbreaking work, which has implications for treating fever, pain and neurodegenerative disorders among others, recently earned her federal funding from the National Institutes of Health, as well as a pair of prestigious awards — the McKnight Scholar Award and the Klingenstein-Simons Fellowship Award in Neuroscience. These awards will support her efforts to determine how specialized cells called sensory neurons monitor temperature-related information that they then convey to the brain. Currently, the precise mechanics of this process aren’t clear. “Our tissues, especially our brains, are extremely vulnerable to temperature,” Du said. “Thankfully, our bodies have an amazing sensation and regulation system to maintain body temperature within a narrow range and to warn us when we are exposed to harmful external stimuli, such as extreme heat or extreme cold. Understanding the individual components of this network and how they operate in concert could be a game-changer for treating a host of disorders, from chronic pain to neurological conditions.” Du will use a revolutionary technique in her research called cryoelectron microscopy, or cryo-EM, which allows scientists to visualize molecular structures in their natural state down to the atomic level — about 1/10,000th the width of a human hair. The structures can then be used to inform development of new compounds that could be potentially used for manipulating thermosensitive ion channels and, therefore, treating temperature-related conditions. Her earlier work with cryo-EM has already borne fruit. Since joining the Institute in 2017, she and her colleagues have resolved the structures of several major drug targets, including TRPM2, a protein integrally involved in temperature regulation. This work was supported by the Institute’s Employee Impact Campaign, which is funded by Du’s colleagues and supported generation of data required to obtain further federal and fellowship funding. “It is thrilling to shed light on such a long-standing scientific mystery,” Du said. “We hope our findings will serve as the basis for new and better treatments and improved patient care.” DR. JUAN DU (LEFT) IN HER LAB WITH VAN ANDEL INSTITUTE GRADUATE SCHOOL STUDENT EMERY HALEY 2 | VAN ANDEL INSTITUTE HIGHLIGHTS OF HOPE VAN ANDEL INSTITUTE HIGHLIGHTS OF HOPE | 3

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