10/3/2018

PITTSBURGH – Magee-Womens Research Institute (MWRI) will award the $1 million Magee Prize to an international team of scientists during the inaugural Magee-Womens Research Summit Oct. 9-10 in Pittsburgh. The prize will fund innovative research in reproductive sciences and women’s health that aims to improve lives globally. 

Finalists for the prize have proposed research projects that tackle diverse problems from cardiovascular disease to congenital heart defects to infertility. On the first day of the summit, each team will present its “big idea,” and the winner will be announced that evening at the Magee Prize Dinner. The prize is funded by the Richard King Mellon Foundation.

The Magee Prize finalists: 

Maternal-Fetal Cell Exchange: Cardiovascular Consequences During and After Pregnancy

During pregnancy, cells from the fetus can pass through the placenta and take up residence within the mother’s body – a phenomenon known as microchimerism – and researchers have noticed that this happens to a greater extent in a woman whose pregnancy is complicated by preeclampsia. Adding to the need for resaerch, preeclampsia is also associated with cardiovascular disease later in life.

Putting together the pieces, team leader Hilary Gammill, M.D., of the University of Washington, hypothesizes that maternal-fetal cells contribute to heart disease in women, both during and after pregnancy.

Gammill is working with Carl Hubel, Ph.D., of the University of Pittsburgh, and Annetine Staff, M.D., Ph.D., of the University of Oslo, who for years have each been following hundreds of women post-pregnancy to determine the risk factors contributing to cardiovascular disease. 

The project allows for the combination of these two cohorts into a larger, more diverse research population, and it inspired Hubel and Staff to look to fetal cells and their gene expression patterns as a potential contributor to heart disease in mothers later in life.

“We have been collaborators and colleagues, the three of us, for a long time, but this prize really pushed us to solidify our goals together,” Gammill said. 
  
The Placental Origin of Congenital Heart Defects

About 20 years ago, Yaacov Barak, Ph.D., of Pitt, noticed that mouse embryos with a particular mutated gene – expressed only in the placenta – suffered fatal defects in both the placenta and the heart. To his surprise, fixing the gene just in the placenta corrected the heart defect.

Barak largely shelved the project until recently, when the field started to take notice of a similar trend among human babies. Those with a congenital heart defect were more likely also to have had a defective placenta during gestation. This finding is significant because heart defects occur in approximately one in 150 live births, but in most cases, what causes the heart to form improperly is not known. Barak’s previous work lead him to suspect the placenta. 

To compete for the Magee Prize, which he hopes to use to pursue this theory, Barak assembled what he refers to as a “dream team,” including placenta expert, Myriam Hemberger, Ph.D., of the University of Calgary, and heart expert Henry Sucov, Ph.D., of the University of Southern California. The team plans to develop a diverse collection of mouse models, which they will use to both solidify the placenta-heart connection and analyze its underpinnings. That information may usher in earlier detection, and potentially, prevention and treatment.

“This prize would give the project legs,” Barak said.

Editing the Human Germline 

In the United States, about 1.3 million people of reproductive age are infertile because they can’t produce viable germline cells – sperm or eggs. Faulty genes are responsible about half of the time.

Alexander Yatsenko, M.D., Ph.D., of Pitt, has spent his career discovering the genes that cause infertility, and Kyle Orwig, Ph.D., also of Pitt, aims to repair them. Together with international collaborators, their goal is to offer new hope to infertile patients.

Katsuhiko Hayashi, Ph.D., of Kyushu University in Japan, and Amander Clark, Ph.D., of the University of California Los Angeles, each bring their expertise with creating germ cells from any cell in the body. Hayashi has demonstrated in mice that skin-derived germ cells can produce eggs, sperm and babies. 

The foursome’s idea for the Magee Prize is to use skin cells of an infertile patient, reprogram them into germ cell precursors and then use gene editing techniques like CRISPR-Cas9 to repair the mutations that cause infertility. Then the team will switch to mouse models to prove that this process can produce healthy babies.

“The Magee Prize will allow us to accelerate the pace of research by combining world-leading expertise to tackle a complex problem,” Orwig, the team lead, said, “The prize also provides funding that doesn’t follow the typical conservative NIH paradigm.”