The exposome, the totality of a person’s exposures and their biological effects, is an increasingly popular research subject. In recent years, researchers have made significant advances in devising ways to measure those exposures and determine how they relate to the risk of developing a disease or certain health outcomes.

Andrea Baccarelli, M.D., Ph.D., presented his work on the subject at the 2024 NIEHS Hans L. Falk Memorial Lecture. Baccarelli, the dean of the faculty at the Harvard T.H. Chan School of Public Health, discussed his efforts to identify the hallmarks of environmental exposures on human cells.

The Nov. 5 lecture was hosted by Alexandra White, Ph.D., NIEHS Environment and Cancer Epidemiology Group lead.

“His work transcends a lot of different research areas across NIEHS, from epidemiology to more basic lab science,” said White. “He's had such a large impact in public health, which is why I think his talk was so meaningful.”

Molecular fingerprints

Baccarelli and his team work to identify the effects of chemical exposures that can result in a variety of consequences to human health. His research has homed in on two biomarkers of environmental exposures. The first is epigenetic changes, modifications to DNA that affect the way genes function without changing the underlying sequence. The second is extracellular vesicles or exosomes, little packages that cells send out to communicate with each other.

He believes that studying epigenetics and exposomes could offer new insights into what a person was exposed to over time. They may also show how those exposures affect various tissues and lead to disease.

“In my research, we use molecular biology together with data science,” said Baccarelli. “We are lucky because environmental exposures leave many types of fingerprints on human cells.”

Epigenetic research

Epigenetic changes can occur via DNA methylation, whereby methyl groups are added to DNA segments. The process can control whether a gene is turned on or off and change its expression over time. As a result, DNA methylation sites can indicate a person's past environmental exposures. Researchers demonstrated the effectiveness of this approach when looking at DNA methylation in smokers.

In one study, Baccarelli and colleagues tested blood DNA samples from nearly 16,000 people. They found that smoking was associated with DNA methylation at more than 7,000 sites, or roughly 40% of a long-term smoker’s genes, compared to someone who had never smoked. In people who only smoked for a few months, more than half of the genes went back to nonsmoking levels. A few years later, almost all went back to nonsmoking levels, but a subset never went back.

“[Studying DNA methylation] creates ways to tell whether someone is a smoker or not, how much someone smoked, and even for how long,” Baccarelli said. “In principle, we can even tell if people quit, how long they quit.”

In the future, Baccarelli said, researchers may be able to assess health with methylation profiling, where a blood test could show how many genes are reacting to certain exposures, such as alcohol, metals, and unhealthy diet.

Extracellular vesicles

Extracellular vesicles are small particles released by various tissues that can be detected in bodily fluids, like blood, saliva, and urine. These particles can reveal information about the cell’s status or environment. If a person inhales particulate matter from air pollution, for example, the lungs may start to produce extracellular vesicles that travel in the blood to the brain, which may increase inflammation and oxidative damage.

NIEHS grants have helped Baccarelli make advances in research on extracellular vesicles, such as exploring their role in environmental epidemiology studies of aging. In the future, he hopes to create an atlas of vesicles created by multiple tissues and make it publicly available.

“We will be able to create data-driven algorithms that predict whether we have been exposed to air pollution or not,” said Baccarelli. “Down the line, they could tell us about our individual risk.”