GRAND RAPIDS, Mich. (Sept. 30, 2021) — Van Andel Institute has welcomed structural biologist and epigenetics expert Evan Worden, Ph.D., to its growing faculty.

Evan Worden, Ph.D.

As an assistant professor in the Department of Structural Biology, Worden will leverage the Institute’s suite of high-powered cryo-electron microscopes (cryo-EM) to investigate the epigenetic mechanisms that contribute to cancer. Cryo-EM allows scientists to visualize molecules in stunning detail at the near-atomic level and provides extensive insights into the nuts and bolts of health and disease.

Worden hopes to shed new light on the genetic and epigenetic roots of cancer and identify targets for improved cancer treatments.

“Our understanding of how epigenetics contributes to cancer has exploded in the last decade,” Worden said. “This opened the door for us to use structural biology to answer really detailed questions about how the genetic elements expressed in cancer are regulated. I’m excited to continue this work at Van Andel Institute.”

Worden is particularly interested in parts of the genome formerly derided as “junk DNA.” In recent years, research has revealed that these areas are home to critical regulatory elements that help decide when genes should be active and when they should rest — a determination that has deep implications for cancer and other diseases.

“Dr. Worden is an exceptional scientist whose expertise and groundbreaking research bridges several fields of great importance to human health — epigenetics, cancer research and structural biology,” said Huilin Li, Ph.D., chair of VAI’s Department of Structural Biology. “He has already made significant contributions to these fields as part of his postdoctoral training. We’re thrilled to welcome him to VAI and look forward to celebrating his future contributions to science.”

Prior to joining VAI, Worden was a postdoctoral fellow at Johns Hopkins University. He has earned numerous awards for his scholarship, including the prestigious Damon Runyon Cancer Research Foundation Postdoctoral Fellowship, the Paul Ehrlich Award for Postdoctoral Research from Johns Hopkins University and the Nicholas Cozzarelli Prize for best Ph.D. thesis from University of California, Berkeley.

Worden is the third faculty member to join VAI in 2021. His recruitment is part of an ongoing strategic initiative to expand and bolster VAI’s research programs.

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ABOUT VAN ANDEL INSTITUTE
Van Andel Institute (VAI) is committed to improving the health and enhancing the lives of current and future generations through cutting edge biomedical research and innovative educational offerings. Established in Grand Rapids, Michigan, in 1996 by the Van Andel family, VAI is now home to nearly 500 scientists, educators and support staff, who work with a growing number of national and international collaborators to foster discovery. The Institute’s scientists study the origins of cancer, Parkinson’s and other diseases and translate their findings into breakthrough prevention and treatment strategies. Our educators develop inquiry-based approaches for K-12 education to help students and teachers prepare the next generation of problem-solvers, while our Graduate School offers a rigorous, research-intensive Ph.D. program in molecular and cellular biology. Learn more at vai.org.

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GRAND RAPIDS, Mich. (Oct. 20, 2021) — Van Andel Institute’s Scott Rothbart, Ph.D., has earned a four-year, $792,000 Research Scholar’s Grant from the American Cancer Society to investigate the mechanisms that power a promising class of potent anti-cancer drugs.

Scott Rothbart, Ph.D.

The drugs, called EZH2 inhibitors, work by targeting an enzyme called EZH2 that has long been of interest to cancer researchers because it interacts with the proteins that support DNA. As such, EZH2 plays a major role in switching genes that regulate cell proliferation “on” or “off” — a process that can lead to cancer if it goes awry. It also helps tumors evade attack by the immune system.

Because of their central role in all aspects of health and disease, proteins and the molecules that interact with them, such as EZH2, often are powerful targets for therapeutic development. Currently, several EZH2 inhibitors are undergoing clinical trials in cancer.

“EZH2 has immense potential to move the needle toward more targeted cancer treatments. We hope to contribute to this important work by defining the spectrum of molecules with which EZH2 interacts to help guide development of more precise therapeutic strategies,” Rothbart said. “I am honored and humbled to receive this award from the American Cancer Society and look forward to uncovering new insights that may help improve treatment for people with cancer.”

In 2018, Rothbart and his collaborators developed a new method to study lysine methyltransferases, the family of enzymes to which EZH2 belongs. Their work revealed that these important molecules interact with far more proteins than previously thought. Proteins are the molecular workhorses of the body and are responsible for carrying out all biological processes.

“We are proud to fund the innovative research by Dr. Scott Rothbart at Van Andel Institute, made possible by dedicated American Cancer Society supporters,” said Kathy Goss, Ph.D., vice president of Regional Cancer Control at the American Cancer Society. “By investing in the research community’s brightest minds and best ideas, we continue to improve the lives of cancer patients and their families and, ultimately, move closer to a world without cancer.”

Scott B. Rothbart, Ph.D., is supported by a Research Scholar Grant, RSG-21-031-01-DMC, from the American Cancer Society.

Click here to learn more about Dr. Rothbart and his scientific journey.

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ABOUT VAN ANDEL INSTITUTE
Van Andel Institute (VAI) is committed to improving the health and enhancing the lives of current and future generations through cutting edge biomedical research and innovative educational offerings. Established in Grand Rapids, Michigan, in 1996 by the Van Andel family, VAI is now home to nearly 500 scientists, educators and support staff, who work with a growing number of national and international collaborators to foster discovery. The Institute’s scientists study the origins of cancer, Parkinson’s and other diseases and translate their findings into breakthrough prevention and treatment strategies. Our educators develop inquiry-based approaches for K-12 education to help students and teachers prepare the next generation of problem-solvers, while our Graduate School offers a rigorous, research-intensive Ph.D. program in molecular and cellular biology. Learn more at vai.org.

Media Contact

Beth Hinshaw Hall
Van Andel Institute
Beth.HinshawHall@vai.org
Office: 616-234-5519
Cell: 616-822-2064

The post American Cancer Society grant to support Van Andel Institute research into anti-cancer medications appeared first on VAI.

Earlier today, we announced that Van Andel Institute Associate Professor Dr. Scott Rothbart has been awarded a Research Scholar Grant from the American Cancer Society. The award will support research into mechanisms that power a promising new class of anti-cancer drugs. 

VAI Voice caught up with Dr. Rothbart to discuss his new project, his scientific journey and the importance of mentorship.

Tell us about the research project funded by the American Cancer Society.

Dr. Scott Rothbart

Dr. Rothbart: My lab studies a set of control switches that help tell our genes when they should be on and when they should off. These “epigenetic” switches play major roles in human development, and faulty switches play causal and reinforcing roles in diseases such as cancer.

For this project, we want to map the precise locations of these switches inside the cell, and we want to better understand which switches are faulty in cancer. Our studies will focus on one type of switch called methylation, which is the target of a promising new class of anticancer drugs called EZH2 inhibitors.

At the molecular level, EZH2 is an enzyme that methylates other proteins. EZH2-dependent methylation of proteins that are tightly associated with our genes has been long-studied for its role in switching genes on and off. This project will consider the extent to which proteins loosely associated with our genes are targets of EZH2, and whether disrupting EZH2 activity toward these loosely associated proteins contributes to the anti-cancer properties of EZH2 inhibitors.

A Research Scholar Grant from the American Cancer Society will support this exciting project and help reveal new insights that we hope will lead to improved cancer treatments.

Notably, my first independent research grant was a postdoctoral fellowship award through the American Cancer Society. It really helped catalyze my research and career — I’m very grateful for their support then and now. 

Why did you become a scientist?

Dr. Rothbart: Science and writing were my two favorite subjects in grade school. Growing up, the way I appreciated the application of science was through medicine, and I thought I would become a medical doctor. My sophomore year of college, I took summer classes at New York University. Through a family friend, I was fortunate to join a lab at NYU Medical Center as an undergraduate research intern. That was a life-changing moment.

This immersive biomedical science research experience had me hooked. Before this experience, I knew little about how scientists do what they do. It’s sounds silly now, but I didn’t really appreciate at the time that I could make an impact in biomedical research and that there was a profession out there where I could wake up in the morning with an (sometimes crazy) idea and go to work to test it. I also realized that there is a lot of writing involved in science. I thought, “This is great! I can pursue this career where I can make scientific discoveries and write all about them.”

This “foot-in-the-door” experience that I had as an undergrad has left a lasting impression on me. I try to pay it forward now that I have my own lab by hosting undergraduate summer interns with the hope that I can provide them with that same “aha” moment that I had back at NYU.

(Interested in an undergraduate research internship at VAI? Learn more here.)

How did mentorship shape your path and your mentorship style?

Dr. Rothbart: My experience as a postdoctoral fellow really shaped the way I think about science, design projects and even how I mentor trainees in my lab. In many ways, my mentorship style is a mix of all the good things I’ve learned from my undergrad, graduate and postdoc mentors.

For example, my graduate and postdoc mentors gave me a good degree of freedom in the lab, which forced me to think independently. I struggled a bit with this early on in my Ph.D., but I think it ultimately helped me become a better scientist and gave me a lot of confidence to lead.

My style is similar in that I don’t micromanage my trainees, but I do ensure that I keep up with people in the lab. One way I do this is through weekly one-on-one meetings. That time is dedicated to the trainee. We talk about experimental progress and plans, big-picture ideas, future directions, and the nuts and bolts of projects. These discussions are a great opportunity to set short- and long-term goals, reset if needed and keep our eyes on the prize. My goal is to support trainees while also building their confidence and empowering them.

What are some things trainees can do to prepare for careers as independent scientists?

Dr. Rothbart: For me, it goes back to writing. I encourage trainees to write as often as possible — applications for fellowships, manuscript drafts, and so on. As a Ph.D. student, I remember being thrown into the process of manuscript preparation — my advisor and I would end up with 40 to 50 drafts going back and forth. There’s a lot of growth and development that comes from being actively involved in the writing process.

As a postdoc, I realized that strong writing skills are key for punching your ticket to the next level as an independent researcher. Writing successful grant applications is an important skill set, not only because it helps secure research funding but because it forces you to really think about the project design and the specific aims, and articulate those ideas clearly to readers. Additionally, the grants I was able to attain as a trainee, such as the American Cancer Society fellowship, were a springboard for my career.

Scott B. Rothbart, Ph.D., is supported by a Research Scholar Grant, RSG-21-031-01-DMC, from the American Cancer Society.

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GRAND RAPIDS, Mich. (Nov. 16, 2021) — Van Andel Institute scientists Patrik Brundin, M.D., Ph.D., Peter A. Jones, Ph.D., D.Sc. (hon), Russell Jones, Ph.D., Peter W. Laird, Ph.D., and X. Edward Zhou, Ph.D., have been included in this year’s Clarivate Highly Cited Researchers List, a distinction marking them as leaders in their fields.

The greatly anticipated annual list identifies researchers who demonstrated significant influence in their chosen area or areas of study through the publication of multiple highly cited papers during the last decade. Their names are drawn from the publications that rank in the top 1% by citations for field and publication year in the Web of Science citation index. Only about 1 in 1,000 scientists in the world make this elite list, according to Clarivate.

Citations, or references, to a scientist’s published work by other researchers is universally considered to be a measure of influence and impact in the scientific community.

“It is increasingly important for nations and institutions to recognize and support the exceptional researchers who are driving the expansion of the world’s knowledge,” said David Pendlebury, senior citation analyst at the Institute for Scientific Information at Clarivate. “This list identifies and celebrates exceptional individual researchers at Van Andel Institute who are having a significant impact on the research community as evidenced by the rate at which their work is being cited by their peers. The research they have contributed is fueling the innovation, sustainability, health and security that is key for our society’s future.”

Patrik Brundin, M.D., Ph.D.

Patrik Brundin, M.D., Ph.D.
Deputy Chief Scientific Officer, Van Andel Institute
Patrik Brundin, M.D., Ph.D., investigates the mechanisms that give rise to Parkinson’s disease, a progressive neurological disorder that affects more than 7 million people worldwide. Brundin’s research is redefining our understanding of Parkinson’s, from how it spreads in the brain and throughout the body to investigating the role of infections in the disease’s earliest stages. His goal is to develop new therapies that slow or stop disease progression or that repair the brain — feats not possible with existing treatments. Along with research in his lab, Brundin chairs the scientific committee of the International Linked Clinical Trials initiative, a program spearheaded by Cure Parkinson’s and supported by VAI that moves repurposed medications into clinical trials for Parkinson’s.

Peter A. Jones, Ph.D., D.Sc. (hon)

Peter A. Jones, Ph.D., D.Sc. (hon)
Chief Scientific Officer, Van Andel Institute
Peter A. Jones, Ph.D., D.Sc. (hon) is a pioneer in epigenetics, a growing field that explores how genes are regulated and that has vast implications for the development of new therapies for cancer and other diseases. His discoveries have helped usher in an entirely new class of drugs that have been approved to treat blood cancer and are being investigated in other tumor types. Jones is a past president of the American Association for Cancer Research (AACR), a fellow of the AACR Academy, a fellow of the American Association for the Advancement of Science, a member of the National Academy of Sciences and a fellow of the American Academy of Arts and Sciences.

Russell Jones, Ph.D.

Russell Jones, Ph.D.
Chair, Department of Metabolism and Nutritional Programming, Van Andel Institute
Russell Jones, Ph.D., investigates metabolism at the cellular level to understand how it affects cell behavior and health, with a specific eye on cancer and the immune system. By revealing how cancer cells use metabolic processes to fuel their growth and spread, he hopes to develop new treatments that help patients by changing the standard of care for cancer. He is an elected member of the College of New Scholars, Artists and Scientists of the Royal Society of Canada and an Allen Distinguished Investigator in Immunometabolism.

Peter Laird, Ph.D.

Peter W. Laird, Ph.D.
Professor, Department of Epigenetics, Van Andel Institute
Peter W. Laird, Ph.D., is an expert in epigenetics, a field that explores when and how the instructions in our genetic code are carried out. Epigenetic mistakes play major roles in cancer and, as such, serve as important targets for new treatments. Laird has developed several cutting-edge technologies, which he leverages to identify crucial epigenetic alterations that convert otherwise healthy cells into cancer cells. He is a principal investigator for the National Cancer Institute’s Genome Data Analysis Network and served in a leadership role for The Cancer Genome Atlas, a now-completed multi-institutional effort to molecularly map 33 different types of cancer.

Edward Zhou, Ph.D.

Edward Zhou, Ph.D.
Senior Research Scientist, Li Lab, Department of Structural Biology, Van Andel Institute
X. Edward Zhou, Ph.D., is a structural biologist whose research explores how the architecture of molecules governs how they work — and how abnormal changes to molecular shape can influence disease. He has contributed to numerous paradigm-shifting discoveries including identification of the structure of a major molecular drug target that can be leveraged to treat a host of diseases, as well as structures that provided revelatory new insights into drought resistance in plants.

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ABOUT VAN ANDEL INSTITUTE
Van Andel Institute (VAI) is committed to improving the health and enhancing the lives of current and future generations through cutting edge biomedical research and innovative educational offerings. Established in Grand Rapids, Michigan, in 1996 by the Van Andel family, VAI is now home to nearly 500 scientists, educators and support staff, who work with a growing number of national and international collaborators to foster discovery. The Institute’s scientists study the origins of cancer, Parkinson’s and other diseases and translate their findings into breakthrough prevention and treatment strategies. Our educators develop inquiry-based approaches for K-12 education to help students and teachers prepare the next generation of problem-solvers, while our Graduate School offers a rigorous, research-intensive Ph.D. program in molecular and cellular biology. Learn more at vai.org.

Media Contact
Beth Hinshaw Hall
Van Andel Institute
Beth.HinshawHall@vai.org
Office: 616-234-5519
Cell: 616-822-2064

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What is cancer?

Cancer is a blanket term for more than 100 related diseases that have a core characteristic in common — unchecked cell growth.

At the most basic level, cancers occur when cells divide out of control, eventually interfering with important processes that keep us healthy. Cancer cells also may spread to other tissues, a process called metastasis.

Cancer cells have an arsenal of tools to help them spread. They can hide from the immune cells that comprise the body’s defense system. They can cause the other cells around the tumor, called the tumor microenvironment, to reroute resources to supply the tumor with needed nutrients. And, unlike healthy cells, malignant cells can divide endlessly.

What causes cancer?

Our bodies are made up of an estimated 37.2 trillion cells, each of which has a particular job and usually operates on a set life cycle. Normally when a cell grows old or becomes damaged, it dies, which makes room for new cells. In cancer, old or abnormal cells survive and continue to divide. In many cancers, they may then form masses of tissue called tumors. In blood cancers, such as leukemia, lymphoma and myeloma, cancer cells are found in the blood, bone marrow, lymphatic system and plasma, respectively.

But what goes wrong? How does a normal cell become a cancer cell?

The answer lies in the instructions that make us human — our genetic code. Ultimately, cancer is the result of errors in these instructions (our genetics) or in the way they are read and acted upon (our epigenetics). There are many ways that this can occur, including:

• DNA replication mistakes: During the normal cell division process, our genetic code is copied and passed on to new cells. Occasionally, mistakes occur, and the code is copied incorrectly. These errors are usually fixed by a cell’s quality control process, but sometimes errors slip through the cracks. Cancer can arise when these errors occur on certain genes, such as those that tell cells when to stop dividing.
• Epigenetic errors: Every cell in the body has the same set of genetic instructions but not all these instructions are needed at any given time or by every single cell. That’s where epigenetics comes in. Epigenetics refers to the processes by which the instructions in DNA are selected and acted upon — akin to reading a single recipe in a cookbook while ignoring the others. Epigenetic errors are present in essentially all cancers; for example, epigenetic errors can switch off a cell’s ability to die when it is damaged, allowing it to grow uncontrollably.
• Genetic inheritance: Some genetic mutations that increase cancer risk may be passed down from generation to generation. An example is mutations to the BRCA1 and BRCA2 genes, which increase the risk of developing breast and ovarian cancers.
• External factors: Many things can cause DNA mutations that may eventually give rise to cancer. Examples include sunlight (skin cancers); viruses, such as certain strains of human papillomavirus (cervical cancer), and bacteria such as Helicobacter pylori (stomach cancer); substances such as asbestos (mesothelioma); and lifestyle choices, such as smoking cigarettes (lung, throat and oral cancers).

How does research impact cancer treatment?

Understanding how cancer works on a basic level allows scientists to develop new ways to treat it more precisely. Here are some examples of areas that are at the forefront of cancer research.

• Epigenetic therapy: Sometimes it’s not a change in the genetic code that causes a problem, but rather an error in the way the code is read. Drugs that target these epigenetic errors — errors literally “on top of” the genome — have been shown to “prime” cancer cells, making them more receptive to other therapies. Van Andel Institute is a global hub for this growing area of research, which holds great promise for finding new ways to treat cancer. Read more about VAI’s epigenetics research here.
• Immunotherapy: Immunotherapies harness the robust strength of the body’s natural defenses to fight cancer. These groundbreaking treatments also may be used in combination with other cancer treatments to bolster their effect. For example, the Van Andel Institute–Stand Up To Cancer Epigenetics Dream Team is investigating whether combining immunotherapy medications with epigenetic drugs may improve treatment of non-small cell lung cancer, bladder cancer, myelodysplastic syndrome, and liver, pancreatic and gallbladder cancers. Read more about the VAI–SU2C Epigenetics Dream Team here.
• Earlier detection: Some cancers, such as pancreatic cancer, are incredibly difficult to detect early, which complicates treatment and can lead to poorer outcomes. VAI scientists are hard at work to find simpler, more effective ways to diagnose these tough-to-catch cancers early and to help sort out which cancers will respond to treatment from those that are resistant to treatment. Read more here.
• Personalized medicine: No two people are the same, and no two cancers are the same. Using cutting-edge techniques to understand an individual’s specific disease helps physicians to tailor treatments that better fit the patient.

The post What is cancer, and how can research help? appeared first on VAI.

GRAND RAPIDS, Mich. (Dec. 7, 2021) — Epigenetics expert Yvonne Fondufe-Mittendorf, Ph.D., is joining Van Andel Institute’s growing faculty, a move that will further expand VAI’s research into the relationship between environmental exposures and cancer.

Yvonne Fondufe-Mittendorf, Ph.D.

Fondufe-Mittendorf will arrive in Grand Rapids in January as a professor in VAI’s Department of Epigenetics. She currently is a professor at University of Kentucky, where she studies the relationship between environmental factors, such as arsenic in drinking water, and cancer risk. Her research has revealed how low-dose arsenic exposure transforms healthy cells into malignant ones — revelations that have significant public health implications.

“Our environment has a profound impact on our health, down to the molecular level. My research addresses some of today’s health challenges by developing a deeper understanding of the mechanisms underpinning this critical relationship,” Fondufe-Mittendorf said. “Van Andel Institute is a global center for leading-edge epigenetics research, and I am thrilled to be part of it.”

Epigenetics is a growing field that explores how and when the instructions in our DNA are used, and what happens when things go awry. Fondufe-Mittendorf investigates how environmental impacts, such as exposures to toxicants, disrupts this intricate process and influences health and disease. Her groundbreaking research — which blends epigenetics, toxicology, bioinformatics and medicine — aims to reveal insights that may be translated into new cancer prevention and treatment strategies.

“Understanding how environmental factors impact disease risk is a critical area of research with massive implications. Dr. Fondufe-Mittendorf’s exceptional work is illuminating previously unknown connections that hold great potential for improving human health,” said J. Andrew Pospisilik, Ph.D., chair of VAI’s Department of Epigenetics. “We are over the moon to welcome her to VAI and look forward to her excellent contributions as a first-rate scientist and collaborator.”

Fondufe-Mittendorf is one of six faculty to join VAI in the past year. Her recruitment is part of an ongoing strategic initiative to expand and bolster the Institute’s research programs.

She earned her bachelor’s and master’s degrees from University of Ibadan, Nigeria, and her Ph.D. in molecular genetics from Georg-August Universitaet, Germany, followed by a successful postdoctoral fellowship at Northwestern University.

Fondufe-Mittendorf has earned numerous awards and accolades for her research and mentorship, including the National Institutes of Health’s IDeA Thomas Maciag Award, University of Kentucky Research Professorship and recognition from University of Kentucky’s Chellgreen Center. She also has been profiled in National Institute of Environmental Health Sciences’ Environmental Factor and the American Society for Biochemistry and Molecular Biology’s Research Spotlight.

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ABOUT VAN ANDEL INSTITUTE
Van Andel Institute (VAI) is committed to improving the health and enhancing the lives of current and future generations through cutting edge biomedical research and innovative educational offerings. Established in Grand Rapids, Michigan, in 1996 by the Van Andel family, VAI is now home to nearly 500 scientists, educators and support staff, who work with a growing number of national and international collaborators to foster discovery. The Institute’s scientists study the origins of cancer, Parkinson’s and other diseases and translate their findings into breakthrough prevention and treatment strategies. Our educators develop inquiry-based approaches for K-12 education to help students and teachers prepare the next generation of problem-solvers, while our Graduate School offers a rigorous, research-intensive Ph.D. program in molecular and cellular biology. Learn more at vai.org.

Media Contact
Beth Hinshaw Hall
Van Andel Institute
Beth.HinshawHall@vai.org
Office: 616-234-5519
Cell: 616-822-2064

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As 2021 comes to a close, so too does Van Andel Institute’s celebration of our 25th anniversary. The Institute’s story began with a vision: to make Grand Rapids a world leader in biomedical research and education, for the betterment of human health for generations to come.

Over the years, we’ve made vital breakthroughs in diseases like cancer and Parkinson’s, and in the areas of cell biology, structural biology, and metabolism and nutrition. We’ve found evidence of the origins of Parkinson’s disease in places you wouldn’t expect, such as the nose and the appendix, and are a powerhouse of epigenetics research, investigating the very code that makes us who we are.

Our commitment to translating discovery into the clinic — where it can help people live longer, healthier lives — remains strong. As part of two collaborations — the Van Andel Institute­–Stand Up to Cancer Epigenetics Dream Team and the Cure Parkinson’s–Van Andel Institute International Linked Clinical Trials initiative — we conduct and support an array of clinical trials designed to find effective new treatments for cancer and Parkinson’s disease, and are excited to continue and expand this work in the coming years.

We also are steadfastly dedicated to developing the next generation of scientists who will build on the foundations laid by our world-class faculty. The expert educators at Van Andel Institute for Education offer cutting-edge science educational programming for K–12 educators and students, and Van Andel Institute Graduate School trains the scientific leaders of tomorrow through a rigorous Ph.D. program in molecular and cellular biology.

We celebrate these achievements but also know that our work is far from done. The Institute is growing, pushing toward a future of boundless potential and innovation.

After 25 years of growth and innovation, there is an immense number of milestones and achievements we could share with you. Here are just a few recent achievements from the Institute. (For a detailed history of the last 25 years at VAI, including notable achievements, awards and honors, please read the special edition of our magazine, Highlights of Hope, here.)

• In November, five VAI scientists were named to the 2021 Clarivate Highly Cited Researchers List, a distinction marking them as leaders in their fields.
• As of winter 2021, VAI recruited six new faculty members who will expand our research capacity.
• VAI scientists earned record-breaking funding support throughout 2021 for their paradigm-shifting work. These awards include two ASAP Awards from Aligning Science Across Parkinson’s, two Maximizing Investigators’ Research Awards (R35), a Ruth L. Kirschstein National Research Service Award (NRSA) Institutional Research Training Grant (T32), a Specialized Programs of Research Excellence (SPORE) Grant from the National Cancer Institute (NCI), a Transformative Research Award from the National Institutes of Health, and many more.
• In August 2021, the Graduate School — which earlier this year moved into a newly renovated building next to the Institute — welcomed its largest and most diverse student cohort yet: 14 students from eight countries.
• Van Andel Institute for Education deftly responded to upheavals in the educational landscape by tailoring its programs to be available online, in-person or a hybrid of the two — positioning us well as a reliable asset to educators everywhere.

These achievements and others could not be accomplished without community. We thank every person, every school and organization, and every family that has contributed to our success over the years. There are countless who invested their time, energy and resources into our work, and we are immensely grateful for the support of our mission through your generosity.

In large part because of this support, VAI has come so far in just a quarter-century. From those early days, with a staff in the dozens and temporary research space at Butterworth Hospital, we’ve grown into an organization of nearly 500 scientists, educators and staff, with work that is recognized around the world.

The Medical Mile continues to spring up around VAI, and we’re proud to be part of such strong investment and growth in the health and biomedical sciences in Grand Rapids. Our founders’ vision set the pace and tone for a bright future where VAI can help lead the charge into a healthier future for all of humankind.

For the latest news and research breakthroughs from VAI, please click here.

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Throughout the year, we highlight Van Andel Institute Graduate School’s doctoral students. This month, we’re featuring Alfredo Reyes Oliveras, a Ph.D. student in the lab of Dr. Brian Haab.  Alfredo studies possible markers in blood or tissue that could help scientists detect, diagnose and better understand pancreatic cancer.

How would you describe your area of study to someone without a scientific background?

Alfredo Reyes Oliveras

My area of study focuses on finding possible biomarkers — molecules expressed only in pancreatic cancer patients — in blood or tissue that could help us detect, diagnose and understand better the disease.

What do you want to do with your degree?

Once I obtain my degree, I want to be involved in translational research, where I can apply the skills I have learned in grad school towards a more direct impact on human health.

What is your primary motivation for persevering through graduate school?

I consider myself a very curious, resilient and ambitious person. These qualities help me persevere and thrive during dark days when experiments are not going as planned.

What accomplishment (academic or other) are you most proud of?

I feel very proud to be the first member of my family to go to grad school.

Why did you choose Van Andel Institute Graduate School?

I chose Van Andel Institute Graduate School because I was looking for a smaller institution with a lot to offer. VAI has appropriately sized classes, problem-based learning coursework and a very specialized focus on research.

Did you take time off before starting your Ph.D. degree or come directly from an undergraduate or master’s degree program?

I did not take time off after my undergraduate degree. I completed a dual degree in chemistry and biology that took me six years. After that, I applied to grad school and came directly to Grand Rapids, Michigan.

How has your previous coursework contributed to your breadth of knowledge?

I would say that doing a dual degree in chemistry and biology came in handy in grad school. Most of the coursework covered during the first year of grad school I had learned during my undergrad years as a biology major. My chemistry degree came in handy in regard to the benchwork, where many assays, techniques and instrumentations are based on chemical approaches.

Do you think there is value in networking with other graduate students in non-related fields?

I consider myself a social butterfly, so I think networking in any aspect has value. You never know who you will encounter in the future. Having connections with people in different fields can help you open doors you thought you could not reach.

Did your past experiences in life or education help prepare you for graduate school, or did you have to develop different strategies to succeed?

Every experience I’ve had has helped me prepare for a challenge like grad school. I have been interested in science since I was young. My parents always supported me in doing science fairs in school, which led me to enroll in a specialized science and math school in Puerto Rico. I also participated in undergraduate research, science clubs, internships, and the MARC program at University of Puerto Rico at Mayagüez, which provides honors students with research-related activities and a specialized science curriculum. All these experiences built my curiosity for science.

Interested in Van Andel Institute Graduate School? Learn more at vaigs.vai.org and read previous student spotlights here. Read more about the M.D./Ph.D. program here.

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Throughout our lives, we’ve been reminded that eating a nutritious diet is important for our overall good health and helps reduce the risk of many cancers, including colorectal cancer.

But there also are many risk factors that are simply part of us. The most familiar are genetics and family history. One you might be less familiar with is epigenetics. Epigenetics is a complex set of processes that determine when and to what extent certain genetic instructions are carried out. Epigenetic processes are essential for healthy cellular function. However, when things go awry, they can play major roles in disease.

One epigenetic process is known as methylation, which acts like a switch that tells the body’s cellular machinery when specific genes should be turned on or off. In cancer cells, these patterns change, impeding the normal checks-and-balances on cell growth and allowing malignant cells to flourish and spread. UHRF1 is a protein involved in epigenetics — a key regulator of biological processes— that can drive colorectal and other cancers. In fact, research from the Rothbart Lab at Van Andel Institute has shown that blocking specific parts of UHRF1 switches on hundreds of cancer-fighting genes, impairing cancer’s ability to grow and spread.

Understanding all the various factors that influence colorectal cancer is crucial. Colorectal cancer is the third most common cancer diagnosed in both men and women in the United States (excluding skin cancers). It’s estimated that 151,030 men and women will be diagnosed with colorectal cancer in 2022. And this year, colorectal cancer is also projected to take the lives of 52,580 men and women in the U.S., the second leading cause of cancer-related death for men and women combined.¹ Rates of colorectal cancer also are rising in younger people who haven’t yet reached the age in which regular screening is recommended. ²

VAI researchers continue to study the role of UHRF1 in an effort to develop new, improved inhibitors to treat colorectal cancer. They’re exploring whether medications that target other epigenetic factors may be a viable approach for better treating the disease. And they hope to leverage molecular profiling of epigenetic processes to help better identify colorectal cancer subtypes and disease stages, improving physicians’ ability to take a personalized approach to treatment.

To learn more about colorectal cancers, visit: vai.org/colorectal-cancer-month-explainer.

References

¹ American Cancer Society. 2022. 2022 estimates. https://cancerstatisticscenter.cancer.org/?_ga=2.239342531.1759875586.1646672622-244632275.1646672621#!/

² Simon S. 2020. Colorectal cancer rates rise in young adults. American Cancer Society. https://www.cancer.org/latest-news/colorectal-cancer-rates-rise-in-younger-adults.html

The post How do molecular ‘switches’ impact colorectal cancer? And what could they mean for treatment? appeared first on VAI.

Van Andel Institute Postdoctoral Fellow Dr. Ben Johnson has earned a Mentored Investigator Grant from Ovarian Cancer Research Alliance to support a groundbreaking approach to ovarian cancer research — adding barcodes to ovarian cancer cells to study how these cancers start, recur and resist treatment. Dr. Johnson, who works in the lab of VAI Associate Professor Dr. Hui Shen, also uses other computational techniques to better understand how ovarian cancers work and how we might be able to better treat them.

We caught up with Dr. Johnson to chat about ovarian cancer research, his project and how Big Data is changing research.

What are some of the challenges in studying and treating ovarian cancer?

Dr. Johnson: Ovarian cancer traditionally has been treated as one disease but, in recent years, it has become clear that multiple subtypes exist with distinct features that present unique challenges in the clinic to treat each type.

The most common subtype is called high-grade serous ovarian cancer and comprises about 75% of total cases — making it one of the most intensely studied types. We have a pretty good idea which tissue it starts in — which is important for understanding how to treat it — but the process of normal tissue transforming into a tumor remains poorly understood. One idea is that a rare population of cells called ovarian cancer stem-like cells might provide a way for high-grade serous ovarian cancer tumors to start, restart and resist treatment.

Understanding this process matters because it contributes to two key challenges of treating ovarian cancer — that is, ovarian cancer usually is detected in the late stages of the disease and comes back in about 80% of cases within five years. By understanding how ovarian cancer stem-like cells turn into all cells that make up a tumor, we can design tests to detect cancer sooner and treatments to specifically target these cells and processes.

Another challenge of studying ovarian cancer is that these tumors are composed of many different cell types, with each individual cell interacting with other cells, all of which function slightly differently. Ideally, we would be able to break the tumor apart into the individual cells and study it in its constituent pieces — single cells. At VAI, we have recently made significant strides to studying these single cells at higher resolution than what has been shown before. These insights help us understand which genetic switches are flipped “on” and which are flipped “off” in the cells — an important indicator of the processes that drive each malignant cell. This new technology (STORM-seq) is helping us understand the roles each single cell is playing in a tumor and begin to answer questions that were not previously able to be addressed.

Tell us about your project. What do you hope to find?

Dr. Johnson: One of the ways ovarian cancer tumors might start is through ovarian cancer stem-like cells. This has significant implications both from a basic understanding of tumor development and impacting treatment decisions in the doctor’s office. If this population of cells is the one that can lead to starting and restarting tumors, we need to develop treatments that specifically target these cells. However, it still isn’t clear how ovarian cancer stem-like cells give rise to the cells that make up an ovarian cancer tumor.

In this project, we are using a system in the lab to give each ovarian cancer stem-like cell a unique barcode that we can then trace as each cell divides into two cells, keeping track of which original cell it came from. This type of system allows us to ask questions about the specific genes and environmental cues, such as those seen within a patient, influence the cell types produced from ovarian cancer stem-like cells.

We hope to find patterns of gene expression that define how an ovarian cancer stem-like cell can “decide” to either make more of itself or produce the cell types that make up an ovarian cancer tumor. These patterns will hopefully reveal targets that we can ultimately develop treatments against, leading to better patient outcomes. I am deeply grateful to Ovarian Cancer Research Alliance for their support of this important project.

What is Big Data and how can it help us move the needle on ovarian cancer?

Dr. Johnson: Within the context of biomedical research, Big Data can be defined as vast data sets collected across hundreds to hundreds of thousands of patients with the goal of identifying patterns or associations that could lead to better patient outcomes. These improvements include earlier detection of disease, stratifying people based on risk or guiding treatment plans.

Notably, during the last decade, The Cancer Genome Atlas (TCGA) consortium made landmark discoveries in many different types of cancer, including ovarian cancer, using large data sets built by profiling many different aspects of tumors. The impact of this work continues to have real-world effects by couching new discoveries in a broader context that would otherwise not be possible.

However, as more and more data are collected by researchers, we need to come up with ways to effectively manage and process all this information to ensure it is used effectively. I believe that large-scale analyses will continue to make significant strides that would otherwise not be possible, but at the same time, there exists a need for high-resolution techniques within individual patients to uncover key processes that might be missed otherwise.

I think this is where the technology we are developing, STORM-seq, fits as a complement to other approaches by providing a precise tool, like a scalpel, to dissect out how these processes are occurring by measuring more features within and across single cells. Together, I think Big Data approaches and our more zoomed-in view of single cells can have a significant impact on ovarian cancer patient outcomes.

Research reported in this publication is supported by Ovarian Cancer Research Alliance [Mentored Investigator Grant, no. 891749}. The content is solely the responsibility of the authors and does not necessarily represent the official views of Ovarian Cancer Research Alliance.

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