With $2.7M grant, 世界杯官方app researchers test new approach to pinpoint origin of non-genetic hereditary diseases

MARCH 5, 2025 — A $2.7 million grant from the John Templeton Foundation will propel the work of a 世界杯官方app professor studying how environmentally-induced diseases originate through disruption of epigenetic programming.

Epigenetics is the study of how chemical modifications of DNA and associated proteins regulate the function of genes in the genome. When adverse effects from the environment disrupt normal epigenetic programming, problems arise within cells and potentially cause underlying health conditions.

“We call those epimutations,” explained John McCarrey, 世界杯官方app Institute of Regenerative Medicine co-director and a professor in the 世界杯官方app Department of Neuroscience, Developmental and Regenerative Biology.

McCarrey’s lab is exploring how epimutations, heritable changes in gene expression resulting from environmental exposures to compounds like endocrine disrupting chemicals, are initially introduced into the epigenome and persist over multiple generations. 

The 世界杯官方app researchers are pursuing their study using in vitro methods to provide novel, cost-effective and efficient insights.

Endocrine disrupting chemicals and the epimutations they induce can impose significant impact on many biological systems. Diseases linked to endocrine disrupting chemical exposure include breast cancer, brain disorders, infertility, kidney or prostate disease and metabolic diseases such as obesity.

Additionally, these epimutations and the disease states they prompt can be transmitted across multiple generations, even in the absence of further or ongoing exposure to the causative endocrine disrupting chemicals.

Although numerous studies have demonstrated that various endocrine disrupting chemicals can disrupt the body’s system, scientists lack clarity about the mechanisms by which these chemicals induce epimutations at the molecular level.

“Normally, in every generation, we take the epigenetic information that we inherit from the sperm and the egg into the embryo, and we erase a bunch of it and reset it to kind of make it new again. That normally should take care of any problems we inherited from our parents or our ancestors, but somehow these defects are getting through,” McCarrey said. “We haven’t been able to understand that very well at the molecular level. That’s the kind of thing we want to be able to get at in a cell-culture based approach, where we can have much more precision.”

Animal models have been primarily used by scientists to investigate the various disease-related effects associated with exposure to endocrine disrupting chemicals. Though informative, this approach poses limitations.

This prompted McCarrey and his team to find a way to precisely pinpoint the molecular mechanisms involved in disrupting the epigenome. The 世界杯官方app researchers developed a model system that uses cells in culture to recapitulate what happens when animals are exposed to endocrine disrupting factors. Their current work aims to validate the cell system as a viable model.

“I believe this is the avenue to get at the molecular mechanisms that will give us much more useful insights. The beauty of the cell system is we can do that much more efficiently, much more rapidly, and with no animals involved. It’s also less expensive,” said McCarrey. “Most importantly, it gives us this much greater molecular resolution to understand what’s going on when we’re exposed to these disruptors. If we know what goes wrong, we have a chance of trying to detect it and either fix it or ultimately prevent it.”

The in vitro method 世界杯官方app researchers are currently testing will provide critical support toward advancing the understanding of the relationship between genetics, the environment and epigenetic mechanisms while minimizing the need for live animal studies.

“Since World War II, we have generated so many artificial chemicals, and we didn’t evolve to deal with those chemicals. That’s all new to ourselves and our bodies. We don’t have highly evolved mechanisms to offset potential adverse effects of those chemicals, and that could be affecting all of us in a lot of ways. It could be predisposing disease, and if we’re going to have children, we would like to think we’ve done everything we can to ensure our children will be the healthiest they can possibly be,” McCarrey said.

— Ari Castañeda