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Exploring the Epigenetic Landscape of Parkinson’s Disease Neuroepigenetics offers unique insight into Parkinson’s disease risk and future therapies. An emerging area of research, known as neuroepigenetics, could provide a new avenue for the development of novel diagnostics and therapies for Parkinson’s—a disease that affects seven to 10 million people globally. If the genetic code is a musical score, then epigenetics represent the various ways in which it may or may not be played. Although the actual notes on the sheet music do not change, the choice of key, instrument, volume and even the omission of parts of the piece alters what the listener hears. In much the same way, epigenetic modifications do not change the DNA sequence—which is virtually identical in all cells in a person’s body— rather, they regulate how the DNA is expressed. Epigenetics control how the DNA is used, switching particular genes “on” or “off” to determine cell type and function. Disruptions in these epigenetic controls also may play significant roles in the development of Parkinson’s and many other diseases. “We know a fair amount about the role of epigenetic mechanisms in cancer, specifically how genes
are switched ‘on’ and ‘off’ inappropriately, but we know far less about how these processes occur and Peter Jones, Ph.D., D.Sc. function in the brain,” said Peter Jones, Ph.D., D.Sc., VARI’s research director and a world renowned epigenetics expert. “There is great potential for epigenetics to revolutionize our understanding of how neurodegenerative diseases occur and progress.”
New appointments, new insights Gerhard (Gerry) Coetzee, Ph.D., and Viviane Labrie, Ph.D., recently joined the Institute to explore the genetic and epigenetic underpinnings of Parkinson’s. Both scientists will utilize cutting-edge techniques to better identify and understand risk factors and causes of neurodegeneration, paving the way for new therapies that slow or stop disease progression. Coetzee, an expert with more than 30 years of experience in molecular biology and large scale genomic studies who joined the Institute from University of Southern California, is well known in the cancer field and
has made several discoveries in both breast and prostate cancers. Currently, he applies his expertise in genetic and epigenetic cancer research to pinpointing specific risk factors for Parkinson’s. “Joining VARI is an incredible opportunity to apply the techniques we’ve used to further our understanding of Gerhard Coetzee, Ph.D. cancer risk factors to Parkinson’s,” Coetzee said. “I have a long career in cancer research and in order to apply my work in genetics to Parkinson’s I require strong, active collaborators. I have found that in my colleagues in the Center for Neurodegenerative Science.”
Less than 10 percent of Parkinson’s cases have a known genetic link. The remaining majority of cases occur have no known cause, although scientists theorize a combination of genetic, epigenetic and environmental factors may be involved. Continued on page 2
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Highlights of HOPE Coetzee’s research utilizes genomewide association studies (GWAS) to link pieces of the genome to physical traits, helping narrow down regions that may be associated with a particular disease. Dozens of pieces of genome variations—called SNPs— have been linked to Parkinson’s, and Coetzee’s research aims to narrow these SNPs down even further and define how they influence risk for neurodegenerative diseases. His work could lead to a roadmap for genomically-based diagnostics and targeted, effective therapies for Parkinson’s. Labrie, who joined the Institute in March from University of Toronto, also searches for risk factors. In particular, her research will identify abnormally regulated regions of the genome and investigate how these areas contribute to Alzheimer’s and Parkinson’s, the two most common neurodegenerative diseases. Labrie’s discoveries could reveal the underlying mechanisms that contribute to the onset and progression of neurodegenerative
diseases and provide new opportunities for early diagnosis and treatment. “Epigenetics may be an important Viviane Labrie, Ph.D. crossroads for both genetic and environmental risk factors for Alzheimer’s and Parkinson’s diseases,” Labrie said. “We know that epigenetic marks are central to the function of healthy brain cells, yet do change within an individual over time and in response to environmental triggers. Knowing how these changes accumulate with age may be important in better understanding Alzheimer’s and Parkinson’s—both of which occur later in life.”
Building on a solid strategy Patrik Brundin, M.D., Ph.D., leads the Institute’s Center for Neurodegenerative Science and looks forward to applying the Institute’s work in neuroepigenetics to the Center’s three strategic areas of focus—disease modification,
identifying biomarkers and restoring brain function.
“As part of our efforts to modify course of Parkinson’s disease, we hope to learn about epigenetic disease mechanisms that we can Patrik Brundin, M.D., Ph.D. target for treatment,” Brundin said. “It’s possible we will find epigenetic biomarkers in blood or peripheral tissues that will tell us who is at risk for getting Parkinson’s before disease onset. We also hope to use epigenetic strategies in cell reprogramming in order to restore brain function. It’s truly an exciting and promising field.”
GLOSSARY Epigenetics: Epigenetics is the study of how the modification and packaging of DNA influences which genes are turned “on” or “off” in a cell. Without changing the actual structure of the genetic code, epigenetic marks control the way genes are expressed. Some epigenetic changes are known to cause cancer and other diseases.
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Searching for the Origins of Ovarian Cancer All cells in the human body have an “epigenetic fingerprint” that acts as a molecular memory. Cancer cells are no exception. By determining and comparing the “epigenetic fingerprints” of specific genomic regions of ovarian cancer cells to those of normal ovarian cell types, Van Andel Research Institute (VARI) Assistant Professor Hui Shen, Ph.D., plans to determine Hui Shen, Ph.D. which of the normal cell types are the origin of the cancer cells. This information will give scientists and physicians a crucial piece of the puzzle when developing new therapies and determining appropriate therapies. To recognize and support her efforts, the Ovarian Cancer Research Fund (OCRF) awarded Shen the Liz Tilberis Early Career Award, a prestigious award given to junior scientific investigators who demonstrate a substantial commitment to an investigative career in ovarian cancer research. OCRF is the oldest and largest charity in the U.S. that funds ovarian cancer research.
Shen joined VARI in 2014 after serving as a research associate at the University of Southern California. She plays an integral role in The Cancer Genome Atlas, a National Institutes of Health-funded, multi-institutional effort to characterize many different cancers. Shen also participates in the work of the VARI–Stand Up To Cancer (SU2C) Epigenetics Dream Team.
“Although researching the origin of ovarian cancer is complex, the goal of my work is simple— to better understand ovarian cancer and to use this knowledge to find ways to intervene earlier,” Shen said. Shen will be speaking about her work during the Institute’s A Conversation About Women’s Health: Common cancers affecting women event on Nov. 16, 2016.
Save the Date! A Conversation about Women’s Health: Common cancers affecting women Presentation and Q+A with Hui Shen, Ph.D. Nov. 16, 2016 11:30 a.m. – 1:30 p.m. Van Andel Institute – 333 Bostwick Ave., NE, Grand Rapids, MI 49503
Become a monthly donor online — it’s easy! Visit www.vai.org/monthly today to set up an automatic monthly donation. Your dedicated support ensures that we can continue to fight diseases and inspire young minds now and in the future—and offer hope to patients and families throughout the world.
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Highlights of HOPE Van Andel Institute Graduate School - Training Top-Tier Scientists Emily Machiela, a Ph.D. candidate at Van Andel Institute Graduate School (VAIGS), investigates new ways to slow and reverse the effects of neurodegeneration caused by diseases like Parkinson’s and Huntington’s. While pursuing her degree, Emily has worked closely with Jeremy Van Raamsdonk, Ph.D., assistant professor in Van Andel Research Institute’s Center for Neurodegenerative Science. Emily joined VAIGS after completing clinical research internships in 2013 at both Mercy Health Saint Mary’s and Mary Free Bed. Her decision to pursue a Ph.D. at VAIGS was based on the program’s distinctive inquiry-based approach. “The opportunity to become an expert who specializes in one area of biomedical research motivated me to enroll in the Van Andel Institute Graduate School,” Emily said. “The program forces me to think critically, ask questions and design creative solutions to problems associated with neurodegenerative diseases. It is the most fascinating and challenging experience of my life.” Collaborating with a small cohort of four people alongside physicians and scientists from a variety of backgrounds has helped Emily develop her professional skill set. Her work in the lab is an integral part of the VAIGS educational experience, and after spending hours conducting research, her peers feel more like coworkers than classmates.
Emily Machiela—Ph.D. candidate at Van Andel Institute Graduate School
“Van Andel Institute Graduate School is not a traditional university setting—I am treated like a working scientist and given a lot of freedom to pursue what I am interested in,” Emily said. “More importantly, I am also held accountable for my ideas by top experts in my field and given access to the tools that help me grow as a scientist.”
NEXGEN INQUIRYTM EXPANDS ITS REACH In 2015, the Institute launched NexGen Inquiry, a web-based science education platform that connects students and teachers from around the world to inquiry-based science education methods. The Institute is in the process of rolling out this exciting new platform. Through a successful outreach campaign, NexGen Inquiry has established: Geographic footprint includes all 50 states and 7 countries
163,000+ browser sessions since launch
1,750 teacher accounts
8,725 student accounts
3,150 investigation templates (made by teachers)
You can help provide NexGen Inquiry for students and teachers by making a gift at www.vai.org/supportnexgen. For more information, contact Teresa Marchetti at 616.234.5040. 4 | Van Andel Institute Highlights of Hope
A Donor’s Story: Love at First Sight— Robin and Mike Schwark Robin met Mike Schwark during their junior year at the University of Michigan. Robin was the business manager of the U-M hockey band and Mike was a young saxophone player. On the first day of rehearsal, Robin noticed Mike looking at her from across the room, and when their eyes met, it was love at first sight. Mike and Robin were married on Halloween. It was a day picked by coincidence, but instead of changing the date, the two embraced the craziness of the holiday and incorporated costumes and decorations into their wedding reception. Mike was a gorilla and Robin was Groucho Marx. Their wedding was the beginning of a beautiful family that would grow to include three sons and serve as a source of strength during Mike’s battle with brain cancer.
Robin and Mike Schwark with their three sons Kallen, Aaron and Adam.
Mike passed away in the family home on Oct. 27, 2014—four days before their anniversary. After Mike’s passing, Robin received an outpouring of support from friends and those who had known Mike professionally. Mike, a financial advisor at Wells Fargo Advisors LLC, had developed a network of hundreds of clients that he treated like family. His long-time business partner and friend, Barbara Paneral, was one of the speakers at Mike’s funeral. “When Mike died in 2014, Barbara and the employees in Mike’s office wanted to honor him, so they hosted fundraisers throughout 2015 to collect funds for Van Andel Institute,” Robin said. “It started out with a pancake breakfast, because Mike loved pancakes, and the fundraisers took off from there.” Mike’s co-workers raised more than $10,000 to benefit brain cancer research at the Institute, and Mike’s name will be added to the Institute’s donor wall during the Leadership and Legacy event in May 2016.
Robin is encouraged by the Institute’s work in brain cancer and is pleased that the funds collected in her husband’s memory went directly to fund research.
“The more I read, the more I discovered that there is real lack of funding for brain cancer research,” Robin said. “When I found out that the Institute was studying brain cancer, I was thrilled.” Mike Schwark was a proud father, a loving husband and a person who touched many lives. Robin believes his legacy is evident in the way he lived, up until the very last moment.
“Mike always said, ‘Whatever can be learned from my experience will help the next person with this cancer,’ Robin said. “He was never angry, nor sad, and he showed our boys how to live during adversity—with love, faith and humor. It was a glorious marriage.”
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Register for the Purple Community® 5K Run/Walk + Fun Run! Get ready for the warm weather running season with Purple Community. Our second annual 5K Run / Walk + Fun Run is scheduled for Saturday, April 30, and 100 percent of the proceeds benefit cancer and neurodegenerative disease research at Van Andel Institute. The 5K takes place at Fifth Third Ballpark in Comstock Park, Michigan. You can get involved in the Purple Community 5K in a variety of ways: • Register as an individual • Form a team by becoming a team captain • Join a team to begin fundraising • Donate and make a difference
Register at purplecommunity.org For information on the Purple Community 5K Run/Walk contact Ashley Owen at Ashley.Owen@vai.org.
AROUND THE WORLD
Around the World, a fine food and wine tasting event hosted by Van Andel Institute’s JBoard Ambassadors in December 2015, brought more than 200 people to the Institute for a night of fundraising and activism. All proceeds from Around the World benefited the Institute’s Pathway of Hope tuberous sclerosis research initiative.
Join the JBoard Ambassadors! JBoard Ambassadors provides a forum, a framework and an opportunity for
building engaging relationships between young professionals and Van Andel Institute (VAI). In addition to various events throughout the year, a donation of $250 includes the following opportunities:
• News and information about VAI’s biomedical research and science education programs • Quarterly Lunch & Learn events • Two complimentary tickets to VAI’s Winterfest Celebration Contact Teresa Marchetti at 616.234.5040 to join the JBoard today! 6 | Van Andel Institute Highlights of Hope
• Professional networking connections • Annual health science forums and luncheons throughout the year • Recognition on VAI’s website and in VAI’s annual report
Starting a New Conversation About Depression More than 18 million Americans have depression, yet it remains one of the most socially stigmatized conditions. It can include a host of symptoms—difficulty concentrating, feelings of guilt, disinterest in usual activities, sleep problems, unhealthy appetite changes and thoughts of helplessness—that make everyday life seem overwhelming. In severe cases, depression can lead to suicide. Last fall, Van Andel Institute addressed the topic of depression during A Conversation About Depression – Hosted by Carol Van Andel. The event was an opportunity for the community to hear directly from experts like Van Andel Research Institute Associate Professor Lena Brundin, M.D., Ph.D.; Eric Achtyes, M.D., assistant professor of psychiatry and director of the Division of Psychiatry and Behavioral Medicine at Michigan State University College of Human Medicine; and Bill Sanders, D.O., psychiatry residency program director at Pine Rest Christian Mental Health Services. Brundin and her team study the role that inflammation— the body’s primary response to infection and other triggers, including autoimmune activity—plays in depression and suicidality. Through a collaborative study with Pine Rest, one of Brundin’s research projects investigates the link between depression and neuroinflammation during pregnancy and the post-partum period. She and her colleagues are searching for better ways to identify women at risk of developing depression while also investigating new treatment options for depression and suicidality during this critical period.
“It’s exciting to think that medications currently used for the treatment of inflammation and infection could help people with depression and become part of a psychiatrist’s toolkit. Research advances are important, but family and friends also play a vital Lena Brundin, M.D., Ph.D. role in helping those with depression,” Brundin said. “It’s often these people that can help identify depressive symptoms while providing a network to help the person seek help and recover from their symptoms. It was a wonderful experience seeing so many people from the community come together to support those with depression.” For information on the Institute’s health advocacy events visit vai.org.
GLOSSARY Anti-inflammatory medication: Anti-inflammatory medications, which include aspirin and ibuprofen, reduce pain, fevers and other inflammation responses in the body. They work by inhibiting the production of chemicals in the body that cause inflammation.
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LEAVING A LEGACY FOR FUTURE GENERATIONS 333 Bostwick Ave NE Grand Rapids, MI 49503
Including Van Andel Institute (VAI) in your estate plans is a great way to make a lasting impact on biomedical research and science education that will benefit generations to come. Donors who include VAI in their estate plans are invited to join the Society of Hope and receive recognition in our annual report. Here are a few planning strategies that can help you provide for your heirs and leave your legacy:
Bequests
Beneficiary designations
Give it twice trust
A bequest made through your will or trust is one of the most common ways to provide from your estate for heirs and favorite charities. You can make a bequest of a dollar amount, specific asset or percentage of your estate.
By completing a simple form, you can designate heirs and charities as the beneficiary of retirement plans, financial accounts and life insurance policies.
You can set up a special charitable remainder trust that will pay income to your heirs and then leave the remaining principle to a charity.
For more information about gift planning, please contact Patrick Placzkowski at 616-234-5030 or Teresa Marchetti at 616-234-5040.
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