Gerhard (Gerry) Coetzee, Ph.D., and Viviane Labrie, Ph.D., will join the Center for Neurodegenerative Science in November and March, respectively. They will utilize cutting-edge techniques to uncover the molecular underpinnings of Parkinson鈥檚 and Alzheimer鈥檚, helping to pave the way to new therapies that slow, stop or reverse disease progression. Their expertise in molecular biology, genome-wide association studies (GWAS) and epigenetics offer novel insight for investigating these diseases and augmenting research already underway at the Institute.
Epigenetic marks play an important role in determining whether a gene is switched 鈥渙n鈥� or 鈥渙ff,鈥� and can contribute to disease development and progression. Neuroepigenetics, or epigenetic modifications in the brain, have been linked to functions such as learning, memory and stress responses, and have been implicated in several neurodegenerative diseases.
鈥淭here is great potential for epigenetics to revolutionize our understanding of how neurodegenerative diseases occur and progress,鈥� said VARI鈥檚 Research Director Peter Jones, Ph.D., D.Sc. 鈥淭his knowledge is critical for the development of new treatment options. We are thrilled Dr. Coetzee and Dr. Labrie are joining our team.鈥�
Shifting the paradigmIt鈥檚 still not clear why people develop Parkinson鈥檚. Scientists know genetics play a role in less than 10 percent of Parkinson鈥檚 cases. The remaining majority of cases occur sporadically with no known cause, although scientists suspect a combination of genetic, epigenetic and environmental factors may be involved.
Neuroepigenetics offers a new approach to uncovering the origins of Parkinson鈥檚, a key step in developing better ways to diagnose and treat the disease and improving the quality of life for the seven to 10 million people around the world with Parkinson鈥檚.
鈥淭here is a strong sense in the global Parkinson鈥檚 community that we鈥檙e on the edge of a paradigm-shifting change in how we diagnose and treat the disease,鈥� said Patrik Brundin, M.D., Ph.D., director of VARI鈥檚 Center for Neurodegenerative Science. 鈥淲hen it comes to the 10 percent of cases that are inherited, we largely know which genes are involved. The addition of Dr. Coetzee and Dr. Labrie鈥檚 expertise will significantly strengthen our existing multidisciplinary team and help us understand how genetic risk factors play a role in the remaining 90 percent of cases, and why some people develop Parkinson鈥檚 disease while others with a similar genetic makeup do not.鈥�
Linking pieces of genetic code to Parkinson鈥檚Genome-wide association studies, or GWAS, is a method that links pieces of the genetic code to physical traits, allowing scientists to narrow down regions of the genome that may be associated with a particular disease. Although dozens of these pieces of code variations 鈥攃alled SNPs鈥攁re linked to Parkinson鈥檚, it is difficult to know precisely how they influence disease risk. It also is challenging to define exactly which gene each SNP influences; although it鈥檚 easy to assume a particular SNP affects a nearby gene,it is possible that the culprit actually is a gene that is located farther away.
As a VARI professor, Coetzee will use GWAS and post-GWAS functional characterization to determine which SNPs truly are associated with the risk of developing Parkinson鈥檚 and how they are linked to disease onset. Much of this work will utilize FunciSNP and motifbreakR, computer software tools developed by Coetzee鈥檚 team that integrates GWAS data along with other genomic and epigenomic information to differentiate functional SNPs from non-functional ones. Coetzee鈥檚 work could provide a roadmap for the development of genomically based diagnostics for Parkinson鈥檚 as well as more targeted and effective therapies.
鈥淕enome-wide genetic associations with complex diseases are at the forefront of modern genetics,鈥� Coetzee said. 鈥淭his has become topical after the human genome was sequenced and the unexpected realization was made that most of our genome does not code for proteins but rather how their expression levels are regulated. The uncovering of such regulatory genetic lesions in the genomes of people with Parkinson鈥檚 will not only lead to a better understanding of the etiology of the disease but also to the development of therapies slowing or halting the disease.鈥�
Coetzee has more than 30 years of experience in molecular biology and human genetics and most recently served as a professor at University of Southern California鈥檚 Norris Comprehensive Cancer Center. He has made several discoveries in the fields of prostate and breast cancer, and has contributed significantly to functional characterization of GWAS data and the understanding of how cancer risk factors actually operate. He plans to continue this work in parallel with his Parkinson鈥檚 disease research.
Linking faulty gene regulation to Parkinson鈥檚 and Alzheimer鈥檚 diseaseLabrie will study epigenetic processes involved in healthy brain function as well as in disease, and explore the complex interplay between genetic and epigenetic features by integrating GWAS and epigenome-wide association studies (EWAS). She aims to identify abnormally regulated regions of the genome and investigate how these contribute to the two most common neurodegenerative diseases鈥擜lzheimer鈥檚 and Parkinson鈥檚. These studies will provide a better understanding of the underlying causes of these diseases and reveal new opportunities for early diagnosis and treatment.
鈥淓pigenetics may be an important crossroad for both genetic and environmental risk factors for Alzheimer鈥檚 and Parkinson鈥檚 diseases,鈥� Labrie said. 鈥淲e 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. The accumulation of these changes with age could be important in Alzheimer鈥檚 and Parkinson鈥檚, both of which occur later in life.鈥�
She currently is an assistant professor at University of Toronto and a project scientist in the Krembil Family Epigenetics Laboratory at the Centre for Addiction and Mental Health. Labrie was among the first to characterize the role of a novel neurotransmitter in the brain and its role in schizophrenia. She also created a new method for mapping epigenetic marks, and has contributed extensively to the field鈥檚 understanding of a particular mark called 5-hydroxymethylcytosine and its impact on brain function.
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ABOUT VAN ANDEL RESEARCH INSTITUTEVan Andel Institute (VAI) is an independent nonprofit biomedical research and science education organization committed to improving the health and enhancing the lives of current and future generations. Established by Jay and Betty Van Andel in 1996 in Grand Rapids, Michigan, VAI has grown into a premier research and educational institution that supports the work of more than 330 scientists, educators and staff. Van Andel Research Institute (VARI), VAI鈥檚 research division, is dedicated to determining the epigenetic, genetic, molecular and cellular origins of cancer, Parkinson鈥檚 and other diseases and translating those findings into effective therapies. The Center for Neurodegenerative Science focuses on the development of novel treatments that slow or stop the progression of neurodegenerative diseases, in particular Parkinson鈥檚. The Center鈥檚 work revolves around three main goals: disease modification, biomarker discovery, and brain repair. The Institute鈥檚 scientists work in onsite laboratories and participate in collaborative partnerships that span the globe. Learn more about Van Andel Institute or donate by visiting . 100% To Research, Discovery & Hope庐
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