GRAND RAPIDS, Mich. (May 31, 2017) – Peter Jones, Ph.D., D.Sc., chief scientific officer of Van Andel Research Institute, has received a 7-year, $7.8 million grant from the National Cancer Institute’s R35 Outstanding Investigator Award program, which will support the development of epigenetic cancer drugs.
Jones is one of 25 recipients of the award in this funding cycle. The National Cancer Institute, part of the National Institutes of Health, launched the program in 2015 to “provide extended funding stability and encourage investigators to embark on projects of unusual potential in cancer research,” according to the funding announcement.
“The NCI Outstanding Investigator Award addresses a problem that many cancer researchers experience: finding a balance between focusing on their science while ensuring that they will have funds to continue their research in the future,” says Dinah Singer, Ph.D., director of NCI’s Division of Cancer Biology. “With seven years of uninterrupted funding, NCI is providing investigators the opportunity to fully develop exceptional and ambitious cancer research programs.”
Leveraging Teamwork and Technology
Among the efforts this award will facilitate are Jones’ cancer epigenetics research, which includes collaborations in the U.S. and abroad; co-leadership of the Van Andel Research Institute–Stand Up To Cancer (SU2C) Epigenetics Dream Team; new drug development; and clinical trials.
“We are very excited about the flexibility and creativity this grant will give us to understand—at the most fundamental levels—how tumors develop and how we can arrest their growth,” says Jones. “We believe this work will result in new drugs, combinations of drugs, and clinical trials that will dramatically improve survival and quality of life for millions of people with cancer and their families.”
Jones also plans to utilize VARI’s new, $10 million suite of cryo-electron microscopes (cryo-EM)—the David Van Andel Advanced Cryo-Electron Microscopy Suite—including a state-of-the art Titan Krios, which gives scientists an unprecedented look at key enzymes, proteins and genetic material at high resolution.
Understanding Epigenomics and Cancer
Nearly 600,000 people die from cancer every year in the United States with another 1.7 million new cases expected to be diagnosed this year, according to the American Cancer Society. The research underway in the Jones Laboratory aims to diminish suffering from cancer for people around the world.
“Our goal is to have a rapid mechanistic and translational impact, leading to new clinical trials for novel cancer treatment and, ultimately, to FDA approval,” says Jones. “This award was possible because of VARI’s interdisciplinary offerings, which allow us to conduct basic science and move our discoveries quickly out of the laboratory and into patient care and clinical trials.”
At the center of Jones’ research is a field called epigenetics, which can be explained using an analogy comparing DNA and a musical score. Just as DNA is nearly identical in every cell in the body, so too do the same notes appear on every copy of a musical score—wherever it’s printed and whenever it’s performed. Musicians must interpret those notes just as epigenetic modifications help interpret the genetic code written in DNA. Subtle changes in key, pitch, instrumentation, volume and tempo vary among performances. Omission of entire movements or changes to instrumentation can more dramatically alter the output. The same is true with DNA—the presence or absence of certain epigenetic modifications affect individual cells’ identity and behavior. When epigenetic modifications go awry, they can lead to the growth and spread of malignant cells.
Advancing Discovery Through Federal Funding
Jones’ work has shed light on the promise of epigenetics and led to a litany of firsts in cancer research and other conditions. Much of this work, and the work of others in the field, builds on Jones’ seminal 1980 discovery about the role of epigenetics in cell differentiation.
These efforts have earned him significant federal funding support over the years, including an R37 Merit Award in June 2009 and a series of R01 awards. Research reported in this publication was supported by the National Cancer Institute of the National Institutes of Health under Award Number R35CA209859. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.
Beth Hinshaw Hall, email@example.com, 616.234.5519
Stephen Baylin becomes third VARI-affiliated scientist to attain the distinction
GRAND RAPIDS, Mich. (May 15, 2017) — Stephen Baylin, M.D., Director’s Scholar and professor in the Center of Epigenetics at Van Andel Research Institute (VARI), has been elected to the National Academy of Sciences (NAS), an independent and nonpartisan advisor to the federal government on matters related to science and technology.
Baylin serves as co-leader of the Van Andel Research Institute-Stand Up To Cancer (VARI-SU2C) Epigenetics Dream Team, in collaboration with VARI Chief Scientific Officer Peter Jones, Ph.D., D.Sc. The VARI-SU2C team currently is conducting four clinical trials that are investigating potential new therapies for colorectal cancer, acute myeloid leukemia, myelodysplastic syndrome and chronic myelomonocytic leukemia.
Baylin is also a professor of oncology at Johns Hopkins University’s School of Medicine and co-director of the Cancer Biology program at the Sidney Kimmel Comprehensive Cancer Center. His research interests include cell biology and epigenetics—the study of modifications that affect how DNA is expressed. He has examined the mechanisms through which variations in tumor cells develop and cell differentiation in cancers, such as medullary thyroid carcinoma and small-cell lung carcinoma.
Additionally, Baylin served on the American Association for Cancer Research Board of Directors from 2004 through 2007 and is an associate editor of Cancer Research. He has authored or co-authored more than 400 publications. In April, he was elected to the Association of American Physicians.
Baylin’s election into the National Academy of Sciences is the latest in a string of honors for Van Andel Institute-affiliated scientists. In addition to three members of the Academy, the Institute also is home to:
The National Academy of Sciences was established in 1863 by an Act of Congress, signed by President Abraham Lincoln as a private, nongovernmental institution to advise the nation on issues related to science and technology. The National Academy of Engineering (NAE) and the National Academy of Medicine (NAM, formerly the Institute of Medicine) were founded under the NAS charter in 1964 and 1970, respectively.
The three Academies work together as the National Academies of Sciences, Engineering, and Medicine to provide independent, objective analysis and advice to the nation and conduct other activities to solve complex problems and inform public policy decisions.
The National Academy of Sciences announced the election of 84 new members and 21 foreign associates in recognition of their distinguished and continuing achievements in original research. To read the entire release, click here.
Peter Jones, Ph.D., D.Sc., is one of 228 new members elected to this year’s class of the American Academy of Arts and Sciences, welcoming him into the company of more than 250 Nobel laureates and 60 Pulitzer Prize winners.
Dr. Jones is the chief scientific officer here at Van Andel Research Institute (VARI). His career traces a path of remarkable firsts—starting with pursuit of epigenetics when few understood its relevance in medicine and there were even fewer willing to embrace this area of research.
Thirty years later, Dr. Jones now leads VARI’s Center for Epigenetics and co-leads the Van Andel Research Institute-Stand Up To Cancer Epigenetics Dream Team, which is testing several new treatments for colon and blood cancers, including acute myeloid leukemia and myelodysplastic syndrome.
“I am honored the Academy has chosen to recognize the work we have accomplished,” says Dr. Jones. “Strong science is a team effort, and I’ve been fortunate to work with incredible colleagues over the years. Our research represents a small contribution to a dynamic field that is brimming with creative, brilliant scientists.”
Established in 1780 during the Revolutionary War, the American Academy of Arts and Sciences stands among the nation’s oldest scholarly institutions with a mission to address social and intellectual issues of common concern.
Dr. Jones’ primary research interest is epigenetics—the body’s DNA control system—and how it contributes to cancer. He ranks among a handful of scientists who pioneered this field, and his discoveries have ushered in an entirely new class of treatments for blood and solid-organ tumors.
His election to the American Academy of Arts and Sciences comes less than a year after being elected to the National Academy of Sciences, which was founded in 1863 during the Civil War and charged with providing independent, objective advice to the nation on matters related to science and technology. Dr. Jones joins VARI Founding Research Director Dr. George Vande Woude, who has been a fellow of the AAAS since 2006.
We’re proud of Dr. Jones’ achievements and recognitions, and we’re excited to see what comes next for VARI and the Center for Epigenetics.
Read more about epigenetics and Dr. Jones’ work here.
The 237th class of members includes philanthropist and singer-songwriter John Legend, award-winning actress Carol Burnett, chairman of the board of Xerox Corporation Ursula Burns, mathematician Maryam Mirzakhani, immunologist James P. Allison, and writer Chimamanda Ngozi Adichie. To read the entire release click here.
GRAND RAPIDS, Mich. (March 28, 2017)—Van Andel Research Institute (VARI) is now home to one of the world’s most powerful microscopes—one that images life’s building blocks in startling clarity and equips VARI’s growing team of scientists to push the limits of discovery in search of new treatments for diseases such as cancer and Parkinson’s.
Cryo-electron microscopy (cryo-EM) is a revolutionary technique that reveals in unprecedented detail the molecular and atomic interactions at the foundation of life, allowing scientists to observe exactly how viruses enter cells, how DNA replicates, how chemical compounds assemble into functional biological components, and much more.
“Our new state-of-the-art cryo-EM facility, which includes significant investments in technology and talent, is part of our unwavering commitment to improve human health through scientific innovation,” says David Van Andel, the Institute’s CEO and chairman. “Not only will it fuel the discovery of life-changing treatments for devastating diseases, but it also will enhance Grand Rapids’ reputation as a destination for outstanding biomedical research.”
Already, cryo-EM has helped uncover the complex structure of Alzheimer’s-related proteins in the brain, overturned long-held assumptions about DNA replication and elucidated the structure of hundreds more molecules implicated in a variety of diseases.
The centerpiece of VARI’s cryo-EM facility is an FEI Titan Krios from Thermo Fisher Scientific, the world’s highest-resolution, commercially available cryo-EM. The Institute’s Krios is only the second in Michigan and one of fewer than 100 in the world. The facility also houses an FEI Talos Artica and an FEI Tecnai Spirit G2 BioTWIN. Overall, VARI invested $10 million in cryo-EM equipment and related construction.
“The resolution available with the Krios, compared to earlier methods, is akin to upgrading from a road atlas to Google Earth,” says Peter Jones, Ph.D., D.Sc., VARI’s chief scientific officer. “It offers exquisite detail of complex systems, which will help us find new therapies so desperately needed for patients around the world.”
Part of the expansion also included hiring three cryo-EM experts: Huilin Li, Ph.D., an established investigator in the field with more than 20 years of experience; Wei Lü, Ph.D., an early career investigator who joined the Institute this month; and Gongpu Zhao, Ph.D., the cryo-EM facility’s manager, who played a key role in the 2013 discovery that revealed the structure of the HIV-1 virus’s outer shell.
Although cryo-EM has been around for decades, recent advances in both techniques and technology have revolutionized the approach, giving researchers powerful new tools to more quickly and more precisely see some of the smallest yet most important biological components in their natural state. These advances led to it being named as the Method of the Year in 2015 by the scientific journal Nature Methods.
“We are very pleased that VARI has chosen the Titan Krios. We have worked hard with leading life science researchers to perfect the capabilities they need to advance their understanding of living systems and disease processes,” says Peter Fruhstorfer, vice president and general manager of Life Sciences, Materials and Structural Analysis, at Thermo Fisher. “The advanced imaging capabilities of the Titan Krios allows scientists to visualize delicate biological structures at the molecular level without damage and in a nearly-natural context, helping them understand the essential relationships between structure and function that are the basis for life itself.”
Before the advances in cryo-EM, a technique called X-ray crystallography was the dominant method of determining molecular structure. However, the approach is very slow and painfully difficult because biological molecules are hard to crystallize. In cryo-EM, the need for crystallization is entirely circumvented. Scientists simply flash freeze molecules or cells in solution. The molecules, now embedded in a transparent thin layer of glassy ice, are then scanned with a powerful electron beam, generating hundreds of thousands of two-dimensional images that are then assembled in a computer into a detailed three-dimensional portrait.
“In a way, biologists are like locksmiths,” says Li. “We use tools such as cryo-EM or X-ray crystallography to see all of the facets of the lock— a normal protein doing its job in a cell or an abnormal protein in cancer, for example—and then use that information to design a key to fit the lock—a drug with the right shape to link up with the protein and alter its function, which may correct the error, ultimately treating the disease.”
Huilin Li, Ph.D.
Cryo-EM Core Director
Professor, Center for Epigenetics
Wei Lü, Ph.D.
Assistant Professor, Center for Cancer and Cell Biology
Gongpu Zhao, Ph.D.
Cyro-EM Core Manager
The Cancer Genome Atlas Research Network recommends clinical trials organizers and drug manufacturers focus on newly discovered molecular subtypes
GRAND RAPIDS, Mich. (Jan. 4, 2017) – A comprehensive analysis of 559 esophageal and gastric cancer samples, collected from patients around the world, suggests the two main types of esophageal cancer differ markedly in their molecular characteristics and should be considered separate diseases.
The study, published today in Nature from The Cancer Genome Atlas (TCGA) Research Network, includes two key takeaways. First, upper esophageal cancers more closely resemble cancers of the head and neck, while tumors further down in the esophagus are virtually indistinguishable from a subtype of stomach cancer. Second, cancer clinical trials should group patients according to molecular subtype—in general, grouping lower esophageal tumors with stomach cancers, while evaluating upper esophageal cancers separately.
“These findings add several layers of depth and sophistication to our current understanding of esophageal cancer genomics,” said Adam Bass, M.D., co-leader of TCGA’s esophageal cancer study and physician-scientist at Dana-Farber Cancer Institute. “Our hope is this work settles several long-standing uncertainties in the esophageal cancer field and will serve as the definitive reference manual for researchers and drug developers seeking more effective clinical trials and new treatment approaches.”
Physicians have known for decades that esophageal cancers, when looked at under the microscope, fall into one of two categories—adenocarcinomas, which resemble stomach or colorectal cancers, and squamous cell carcinomas, which are similar to some lung, skin, and head and neck cancers. What remained unknown was the extent to which adenocarcinomas and squamous esophageal cancers differ molecularly and the relationship between esophageal adenocarcinoma and stomach adenocarcinoma.
“We have shown that these clinical subtypes differ profoundly at the molecular level,” said Peter W. Laird, Ph.D., a principal investigator in the international TCGA Research Network and a professor at Van Andel Research Institute. “These findings suggest that whether the tumor originates in the esophagus or the stomach is less relevant than the molecular characteristics of the individual tumors.”
Esophageal cancer represents just 1 percent of new cancer diagnoses in the U.S. However, it kills 4-in-5 patients within five years of diagnosis, and current treatment approaches often fail to help. Additionally, cases of esophageal adenocarcinoma have skyrocketed over the last four decades, increasing seven-fold since the mid-1970s. Within the field, there has been great uncertainty regarding the relationship between this growing burden of esophageal adenocarcinoma and adenocarcinomas that occur in the stomach.
Results from this new report argue against the need to continue to debate the demarcations of esophageal and gastric adenocarcinoma and instead view gastroesophageal adenocarcinoma as a more singular entity, analogous to colorectal cancer. Specifically, this study revealed that esophageal adenocarcinomas have striking molecular similarity to a class of stomach cancers called chromosomally unstable tumors, the hallmark of which are significant structural chromosomal aberrations.
Oncologists say this nuanced view of the disease, including the detailed molecular taxonomy of esophageal adenocarcinomas, will likely change their approach to studies and treatment.
“It is clear from the TCGA data that esophageal squamous and esophageal adenocarcinomas are completely different diseases and should never be included in the same therapeutic trial,” said Yelena Y. Janjigian, M.D., a gastrointestinal oncologist from Memorial Sloan Kettering Cancer Center who contributed samples to the study and served as a co-author. “In esophageal adenocarcinoma, it is likely a combination of pathways and therapeutic strategies that will be successful. The therapeutic significance of these alterations will be explored in follow-up studies.”
Members of the TCGA Research Network team say these studies represent the work of dedicated collaborators, who seek to maximize results in search of new ways to battle cancer.
“Studies from TCGA transcend the work of any one institution or individual,” said Ilya Shmulevich, Ph.D., a principal investigator in the international TCGA Research Network and a professor at the Institute for Systems Biology. “These are massive undertakings that are possible only through contributions from hundreds of specialists and scientists around the world—people dedicate years of their lives to these projects in the hope of finding new treatments for people who are very sick.”
Peter W. Laird, Ph.D.
Professor, Center for Epigenetics
New data published today shows drug preserves critical brain function in laboratory models of Parkinson’s
GRAND RAPIDS, Mich. (Dec. 7, 2016)—A new investigational drug originally developed for type 2 diabetes is being readied for human clinical trials in search of the world’s first treatment to impede the progression of Parkinson’s disease following publication of research findings today in the journal Science Translational Medicine.
“We hope this will be a watershed moment for millions of people living with Parkinson’s disease,” says Patrik Brundin, M.D., Ph.D., director of Van Andel Research Institute’s Center for Neurodegenerative Science, chairman of The Cure Parkinson’s Trust’s Linked Clinical Trials Committee, and the study’s senior author. “All of our research in Parkinson’s models suggests this drug could potentially slow the disease’s progression in people as well.”
Until now, Parkinson’s treatments have focused on symptom management. If successful in human trials, MSDC-0160 would be the world’s first therapy to treat the underlying disease and slow its progression—potentially improving quality of life and preventing the occurrence of falls and cognitive decline. It may also reduce or delay the need for medications that can have debilitating side effects, says Brundin.
Parkinson’s disease afflicts between 7-10 million people worldwide, including an estimated 1 million Americans, and these numbers are expected to increase dramatically as the average human lifespan increases. There is currently no cure, and first-line treatment has remained relatively unchanged since the introduction of levodopa in the 1960s.
Tom Isaacs, a co-founder of The Cure Parkinson’s Trust who has lived with Parkinson’s for 22 years, says MSDC-0160 represents one of the most promising treatment the Trust’s international consortium has seen to date.
“Our scientific team has evaluated more than 120 potential treatments for Parkinson’s disease, and MSDC-0160 offers the genuine prospect of being a breakthrough that could make a significant and permanent impact on people’s lives in the near future,” says Isaacs. “We are working tirelessly to move this drug into human trials as quickly as possible in our pursuit of a cure.”
MSDC-0160 was developed by Kalamazoo, Michigan-based Metabolic Solutions Development Company (MSDC) to treat type 2 diabetes. In 2012, Brundin recognized it as an exciting drug candidate because of its mode of action, proven safety in people, local availability and the start-up company’s interest in collaborating on drug repurposing initiatives. After four years of work, the effects of the drug in the laboratory exceeded Brundin’s expectations.
The novelty of MSDC-0160 stems from a recently revived revelation that Parkinson’s may originate, at least partially, in the body’s energy metabolism. The new drug appears to regulate mitochondrial function in brain cells and restore the cells’ ability to convert basic nutrients into energy. Consequently, the cells’ ability to handle potentially harmful proteins is normalized, which leads to reduced inflammation and less nerve cell death.
“Parkinson’s disease and diabetes may have vastly different symptoms with unrelated patient outcomes; however, we’re discovering they share many underlying mechanisms at the molecular level and respond similarly to a new class of insulin sensitizers like MSDC-0160,” says Jerry Colca, Ph.D., co-founder, president and chief scientific officer of MSDC.
While Brundin says he is eager to see MSDC-0160 launched into a clinical trial in Parkinson’s disease, he’s equally excited about the possibility of testing the drug in Lewy body dementia and other cognitive decline conditions, such as Alzheimer’s disease.
“This is an immensely promising avenue for drug discovery,” says Brundin. “Whatever the outcome of the upcoming trial for Parkinson’s, we now have a new road to follow in search of better treatments that cut to the root of this and other insidious diseases.”
The Cure Parkinson’s Trust and Van Andel Research Institute are currently working with MSDC to address regulatory issues and obtain funding to organize the clinical trial, which Brundin hopes can begin sometime in 2017.
Funding for the research was provided by Van Andel Research Institute, The Cure Parkinson’s Trust, the Campbell Foundation, and the Spica Foundation.
The paper’s authors include Anamitra Ghosh, Trevor Tyson, Sonia George, Erin N. Hildebrandt, Jennifer A. Steiner, Zachary Madaj, Emily Schulz, Emily Machiela, Martha L. Escobar Galvis, Jeremy M. Van Raamsdonk and Patrik Brundin, all of Van Andel Research Institute; William G. McDonald and Jerry R. Colca, both of Metabolic Solutions Development Company; and Jeffrey H. Kordower, of Rush University Medical Center and Van Andel Research Institute.
Patrik Brundin, M.D., Ph.D.
VARI Associate Director of Research
Professor and Director of the Center for Neurodegenerative Science
Jay Van Andel Endowed Chair in Parkinson’s Research