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2015 Fall Highlights of Hope

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FALL

FALL 2015 VAN ANDEL INSTITUTE’S HIGHLIGHTSof HOPE The Self-Mending Heart When esteemed scientist and cardiologist Dr. Stefan Jovinge was a medical student he learned human heart cells did not possess the capacity to regenerate. Now, as head of a laboratory at Van Andel Research Institute (VARI), director of the DeVos Cardiovascular Research Program (a joint effort between VARI and Spectrum Health) and medical director of research at the Frederik Meijer Heart and Vascular Institute, Jovinge has proven that theory wrong. In a groundbreaking paper published this summer in the scientific journal Cell, Jovinge and collaborators at Karolinska Institute in Sweden outlined a striking discovery—not only does the human heart have the capacity to regenerate muscle cells, which they demonstrated previously, but this regeneration occurs in multiple sites throughout the heart muscle. Additionally, cellular turnover occurs several times in a human life span, but the number of cells hits a threshold at 3.2 billion. The Path Toward Regenerative Therapies This recent finding builds on the group’s 2009 Science paper, where Jovinge and his collaborators first described the heart’s potential for regeneration via the production of cardiomyocytes, the heart’s muscle cells. Still, the discovery left Jovinge with many unanswered questions that led to their new study. “Is the generation of cardiomyocytes restricted and generated from certain locations in the heart? Is the heart increasing in size mainly by adding more cells? And how does the growth and expansion of the other cells in the heart occur?” Jovinge said. “The prospect of using the heart’s inherent capacity to Dr. Stefan Jovinge generate heart muscle cells in adults to make the heart repair itself requires answers to these questions. Our new discoveries do that.” Annually, about 735,000 people in the U.S. have a heart attack, according to the Centers for Disease Control and Prevention. These latest findings provide avenues to understand the source for heart cell regeneration and bring the field one step closer to developing therapies that regenerate heart tissue to repair damage from injuries, such as heart attack. Revolutionizing Treatment Options Annually, about 735,000 people in the U.S. have a heart attack, according to the Centers for Disease Control and Prevention. Current therapies for injury to the heart muscle may involve lifelong drug treatment or surgery such as a heart transplant—none of which actually repair damage. Jovinge and his team are working diligently to find the individual cell types responsible for heart muscle regeneration, and aim to uncover how this process is regulated in order to develop the next generation of cardiac therapies. Jovinge’s work changes the way these treatments will be developed and provides hope that one day the heart can be stimulated to mend itself. Learn more or support Dr. Jovinge’s work at vai.org. Dr. Karsten Melcher Dr. H. Eric Xu Two VARI Scientists Make Big Waves with Recent Discoveries It was a busy summer for Van Andel Research Institute (VARI) structural biologists Dr. H. Eric Xu and Dr. Karsten Melcher. In recent months, the duo made two groundbreaking discoveries, each of which were highlighted in prestigious journals. The first was a highly anticipated paper in Nature that describes the molecular structure of a major pharmacological target. Using the brightest X-ray laser in the world, housed at SLAC National Accelerator Laboratory in California, Xu and Melcher’s teams, along with collaborators at 25 institutions around the globe, uncovered the structure of a signaling protein bound to a receptor that belongs to one of the largest protein superfamilies. Named G protein–coupled receptors (GPCRs), this group of molecules is targeted by more than 30 percent of the drugs currently on the market, and has great promise for future drug development. In the first week of its publication, Xu and Melcher’s Nature paper was viewed more than 20,000 times by scientists from across the world. The groundbreaking work provides investigators searching for new therapies for cancer, Parkinson’s disease and other disorders with much needed information to develop better and more effective treatments. The second paper, published in Science Advances, describes how components of a molecular switchboard in plants interact to turn certain genes on or off in response to a multitude of stressors, including temperature fluctuations. The findings provide further insight into human molecular mechanisms and give scientists a general model across species for this type of gene silencing. Each of these discoveries is important in its own right, but taken together they provide an extensive look into molecular pathways that may be harnessed to treat cancer and other diseases. Your donations make a difference. Please visit www.vai.org or call (616) 234-5030 to support Dr. Xu and Dr. Melcher’s work. 2 | Van Andel Institute Highlights of Hope Van Andel Institute Highlights of Hope | 3

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