On an average New Jersey evening in 1990, Marisa Bartolomei, a post-doctoral student at Princeton University, was up well past her bedtime.
She was working in her epigenetics laboratory, waiting on the results of an experiment she ran on a mysterious gene her and her post-doctoral advisor suspected might be imprinted. The gene, called H19, was highly active during embryonic and fetal development, and since over expression of the gene led to lethality in mice, Dr. Bartolomei hypothesized the gene might be imprinted—a novel concept in 1991.
Imprinted genes are different from traditional genes, which exist as two copies in DNA (one coming from each genetic parent) and are expressed from both copies. Imprinted genes are different, as they express only one of their copies.
Late into that night, Dr. Bartolomei saw that the experiment was complete. She was overwhelmed with the results: H19 was an imprinted gene, and she had just discovered it. As only the third imprinted gene discovered—there have been about 200 more named since—the news was electric.
And the rest, as they say, was history.
Dr. Bartolomei published her findings in Nature; went on to make vital connections between imprinted gene defects and developmental diseases affecting babies in the womb; helped the scientific community understand the importance of properly functioning imprinted genes on healthy pregnancy and development; and continued to publish work that helped lead to new screening tests for developmental diseases.
Just this month, she won the coveted March of Dimes Richard B. Johnston, Jr., MD Prize, one of science’s biggest lifetime achievement awards. The Prize honors an outstanding researcher who has advanced understanding of pregnancy, birth, and prenatal development.
“We are truly just getting started with imprinted genes,” Dr. Bartolomei, who is a Co-Director of the Epigenetics Institute at the University of Pennsylvania’s Perelman School of Medicine and the Perelman Professor of Cell and Developmental Biology, told March of Dimes.
“As scientists like me continue to discover the vital role these genes have on development, others are working on new screening tests, therapeutics, and interventions to ensure we can create treatments for imprinted gene mutations so babies can avoid the worst outcomes.”
Over the course of her career, Dr. Bartolomei has made instrumental discoveries in how imprinted genes are expressed or suppressed. Her work has also illuminated the negative effect environmental exposures such as air pollution, Bisphenol A (BPA), phthalates, lead, and dioxins can have on imprinted genes and fetal development throughout life and pregnancy.
March of Dimes Chief Scientific Officer Dr. Emre Seli called her body of work “truly astounding,” adding that without her efforts, “we would be much further from the development of critical diagnostic and therapeutic interventions” for babies with rare yet severe developmental diseases.
In three plus decades, Dr. Bartolomei has made indispensable contributions to the complex and uncharted field of imprinted genes, several hundred of which exist in each human being.
Unlike traditional genes, which are capable of expressing both copies (one from the mom and one from the dad), imprinted genes operate normally when they only express one copy, not two. In the case of an epigenetic mutation in an imprinted gene, that gene will behave abnormally and express either both of its copies or none of them, leading to developmental errors in the embryo and resulting fetus.
After discovering H19 to be imprinted, Dr. Bartolomei and her laboratory discovered connections between two imprinted genes—H19 and IGF2—and a pair of developmental disorders affecting babies in the womb: Beckwith-Wiedemann Syndrome, which causes babies to grow too big in the womb and predisposes them to cancer, and Silver-Russell Syndrome, which causes babies to grow too slowly in utero.
Just as important, she discovered the exact pathways of gene imprinting defects; namely, that abnormalities in DNA methylation, a vital biochemical process, cause imprinted gene mutations that result in under- or over-expression of the gene, both problematic for the developing fetus.
She also uncovered that while most genes get reprogrammed after egg and sperm come together in fertilization, imprinted genes remain as they were prior to the union, persisting in this way over a lifetime.
Finally, she’s also shown that an imperfect in vitro fertilization (IVF) embryo culture (the liquid environment embryos are created in inside a laboratory) may be linked with gene imprinting defects and disease.
“We’ve come a long way since that day in 1991,” Dr. Bartolomei said, “and we’ve still got a ton to learn from imprinted genes.”
“And I’m just as eager to uncover the mysteries as I was more than 30 years ago.”
March of Dimes will present the award to Dr. Bartolomei at the 2024 Annual Meeting of the Society for Reproductive Investigation (SRI) in Vancouver, British Columbia on March 16, 2024.
Find more information about the PRIZE here, and read the press release on Dr. Bartolomei’s win here.