Project Description

Van Andel Institute, MHIR scientists earn $9.6M NIH Transformative Research Award

October 2021

Van Andel Institute’s J. Andrew Pospisilik, Ph.D., and MaineHealth Institute for Research’s Joseph Nadeau, Ph.D., have earned a five-year, $9.6 million Transformative Research Award from the National Institutes of Health to answer a set of questions that could fundamentally transform our understanding of health and disease: If you were born multiple times under the exact same circumstances, would you turn out to be the same person each time? And if not, what implications could the differences have for your health?

Although it may sound like science fiction, the answers could revolutionize our understanding of how “probabilistic” variation influences health before birth and throughout life — and provide insights into new strategies for combating cancer, obesity and a host of other health concerns and diseases.

This groundbreaking research is made possible by a Transformative Research Award, part of the NIH Common Fund’s High-Risk, High-Reward Research Program. The award promotes cross-cutting, interdisciplinary approaches to projects that have potential to create new paradigms or challenge existing ones, according to NIH.

“In some ways, our health is like a game of dice in which chance, or ‘variation,’ plays a major role. We want to understand exactly how variation defines our health and how we can leverage it to combat disease,” Pospisilik said. “As scientists, we’re trained to see variation as ‘error,’ but we believe that it is actually a necessary and vital biological regulatory process. We are grateful to the National Institutes of Health Common Fund for its support of this exciting project. These high-risk, high-reward funding mechanisms from the NIH are a rare opportunity to peek into the unknown — to remind ourselves how little we actually know.”

Variation is built into every species on earth and is thought to promote resilience against threats such as disease and environmental shifts. However, the genetic and epigenetic regulators that control variation have been difficult to identify and even more challenging to directly link to clinical outcomes.

“Our genes and our environment are just 50% of what makes us who we are,” Nadeau said. “We want to understand what that other 50% is so that someday we may be able to predict whether early medical interventions or lifestyle changes could improve our chances for a healthy life.”

Now, thanks to advances in technology and technique, Pospisilik, Nadeau and their collaborators will be able to detect and analyze the genetic and epigenetic factors that control variation patterns and link them to their effects.

To do so, they will leverage tools created by Nadeau and MHIR’s Christine Lary, Ph.D., (also a collaborator on the award) that allow scientists to identify molecular regulators of variation. Another team at VAI, led by Tim Triche, Jr., Ph.D., will support this effort to push current methodologies beyond their current limitations. Finally, teams lead by Ruth Loos, Ph.D., of the Icahn School of Medicine at Mount Sinai, David Carey, Ph.D., of Weis Center for Research at Geisinger, Neerja Karnani, Ph.D., of Singapore Institute for Clinical Sciences and Peter Gluckman, MBChB, MMedSc, M.D., FRS, of Singapore Institute for Clinical Sciences and University of Auckland will help place Pospisilik and Nadeau’s novel discoveries into real-world, clinical context.

By the end of the study, the team hopes to identify new sets of disease-related genes, delineate subtypes of disease, and better understand how the complex interaction between genetics and epigenetics impacts health.

The research described is supported by the Office of the Director of the National Institutes of Health under award no.1R01HG012444 (Pospisilik and Nadeau). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.