New VARI Initiative Aims to Understand How Metabolism Drives Disease

Back in the 1990s, dietary fat was considered “Enemy Number One.” In the late ’80s, new research had found that a diet high in saturated fat was a major cause of poor health, so a low-fat food craze was born. Cookies, crackers, cake, ice cream, bread—just about everything had a low-fat version in the ’90s. But by 2001, Americans were fatter than ever. What happened?

My food scientist sister helped explain it to me: After removing the fat, food companies needed a way to maintain the original flavor, so they (sometimes dramatically) dialed up the sugar and salt content of the low-fat items. Plus, people patted themselves on the back for making smart food choices and then proceeded to wildly overeat. Almost as quickly as it started, the low-fat craze fizzled.

Fast forward to today, and we’re still trying to figure out how to eat for optimal health. We’ve learned more about what different diets do for our bodies, and now researchers are zeroing in on a new enemy: sugar.

We’ve long known it rots teeth and is loaded with calories, but doctors are also learning that sugar wreaks havoc on cell function and disease progression. With that in mind, the Grand Rapids, MI-based nonprofit Van Andel Research Institute (VARI) has launched what it hopes will be the most comprehensive research program of its kind to investigate the ways metabolism and nutrition drive health and disease.

“Metabolism is one of the oldest molecular sciences,” says Andrew Pospisilik, the incoming director of VARI’s Institute of Epigenetics. “Up until about a decade ago, we thought of it as housekeeping: every cell needs energy, and it’s that simple. What has exploded in the past 10 years is that it’s not true. Every cell has its own fingerprint for how to use metabolism. It drives cell outcomes and defines how they do their jobs—it shapes whether it’s a passive T cell or keeps allergies at bay or attacks cancer.”

What’s become clear to Pospisilik and other researchers is that metabolism is at the center of every single biological process. Some diseases might be “wholly metabolic in origin,” such as diabetes, while others, including cancer, are influenced by metabolic dysfunction. For example, there is increasing evidence that Parkinson’s disease, a degenerative movement and neurological disorder, appears to be partly caused by disruptions in cellular metabolism.

“In cancer, metabolism is really important for cells,” says Russell Jones, who will lead VARI’s new metabolism and nutrition initiative. “What we’re doing now is trying to understand road maps. If a cancer cell has a mutation, how does it reset metabolism to fuel growth?”

Jones says that in the past 30 years, the prevalence of “modern world diseases”—Alzheimer’s, asthma, and diabetes, for example—has skyrocketed, but the genetic pool hasn’t changed much. “There is evidence that sugar is connected. It makes cells more aggressive and it accelerates neurodegeneration.”

The team at VARI working on the initiative is made up of six scientists who each have different areas of expertise, including nutrition, genetics, and immunology. Three, including Jones, previously worked at Quebec’s McGill University, and two are coming to VARI from the Max Planck Institute of Immunobiology and Epigenetics in Freiburg, Germany.

Jones says their work will include identifying factors that contribute to cancer, diabetes, and other disorders, and then understanding how metabolism and nutrition impact cell function. From there, the scientists will aim to translate their research discoveries into products and strategies to improve public health.

Other goals include determining how a parent’s nutrition and environment can influence health of their future children, as well as to what extent people can escape their genetic fate. This last part—how parents can affect children that aren’t even a twinkle in their eyes yet—is at the vanguard of epigenetic research, Pospisilik says. (While the program is not necessarily focused on developing new drugs, VARI has an intellectual property team that will work with the medical community to commercialize findings if appropriate, Jones says. However, some companies are working specifically on drug research related to metabolism, including Kyn Therapeutics and Agios Pharmacueticals.)

“Since every organism starts with a single cell, how do parental cells go into the sperm or egg and cause lifelong changes in their offspring? It’s very difficult to study, but we already have data suggesting much of obesity is caused by genetic reprogramming,” he adds. “We’re fortunate to assemble a diverse team of scientists and top equipment, and we can get everyone together in the same room to discuss it. Within five years, we want the program to be viewed as a center of excellence for this type of research.”

Ultimately, Pospisilik says, the goal of VARI’s initiative is to fully understand metabolism’s impact on cell processes and find strategies to improve human health. “If we can identify, cure, and treat diseases, it will catalyze other centers here at VARI. Metabolism unites them all.”

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