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42 Robert WoodJohnson
I
MEDICINE
W
e see preterm labor far too often," explains Dr.
Rosen, who also is director of the Regional
Perinatal Center at Robert Wood Johnson Uni-
versity Hospital. "It is the number one cause of infant death
in the United States, and children who do survive may have
disabilities throughout their lifetime."
Dr. Rosen knows he has arrived at yet another critical junc-
ture in what has become his life's work. He and his research
team, which is working to understand the basic processes of
labor, may have achieved a breakthrough that could lead to
understanding the underlying causes of some case of preterm
labor.
"In the United States, preterm births are substantially
higher than they were in 1990, and the majority of avail-
able therapies do not help prevent preterm labor," he says.
"If we can understand what drives typical labor with a full-
term pregnancy--why women go into labor when they
do--then we may be able to find a therapy to avoid or stop
early labor and prevent death or disabilities in infants as a
result of preterm birth."
Dr. Rosen's excitement is palpable as he shares the news
of an impending publication, even as he cautions that it is
only a breakthrough, one that will take more study before
it has a direct benefit on his high-risk pregnancy patients.
Valeria Di Stefano, MD, assistant professor of obstetrics,
gynecology, and reproductive sciences, who previously
worked in Dr. Rosen's research lab as a fellow in maternal-
fetal medicine, concurs.
"It is very hard to predict when our discovery could benefit
expectant women," she says. "However, I am confident that
the information we obtained thus far will provide the building
blocks to understand the mechanisms that surround the onset
of labor, and therefore uncover possible targets for therapy."
As a physician and mother of two--who was on mater-
nity leave when the team's research study was published--
Dr. Di Stefano understands the importance of melding
research and clinical care.
"As physicians, we are constantly reviewing the newest
studies and the latest literature to provide our patients with the
most up-to-date, evidence-based treatments," Dr. Di Stefano
explains. "Completing a fellowship in maternal-fetal medicine
has afforded me the opportunity to treat women experiencing
high-risk pregnancies and participate in various cutting-edge
research projects.
"Within our lab, we test theories and possible mechanisms
of actions that I believe will ultimately become the foundation
for determining future standards of care," she says. "We are
filling a void of knowledge in the field of obstetrics."
Three floors above where Dr. Rosen and Dr. Di Stefano
provide care to mothers-to-be is the perinatal research labo-
ratory, an ideal location for the translational research that
could end the leading cause of major illness and mortality in
newborn infants.
In this clean and unusually orderly lab, Bingbing Wang,
PhD, assistant professor of obstetrics, gynecology, and repro-
ductive sciences, has been working since 2010 to determine
the molecular mechanism that regulates labor in a full-term
pregnancy. A physician in his native China, Dr. Wang came
to the United States to obtain a doctoral degree in the molec-
ular biosciences and has since focused on translational
research, first in cancer and now maternal-fetal medicine.
Dr. Rosen and Dr. Wang have conceived numerous ideas
about the process of labor, with a specific focus on designing
experiments to test their hypotheses that the clock which
determines the length of pregnancy resides in the placenta. In
fact, the investigators have come to believe that the placenta
has a primitive "brain" that can decide when it is safe to
deliver the baby.
"This is an important theory, in which we hope to find
concrete answers," says Dr. Wang.
The team's latest research study, published during the sum-
mer in the journal Science Signaling, did just that by identify-
ing the signaling pathway that induces labor in full-term preg-
nancy. It is the breakthrough they have been working toward.
"We found an epigenetic switch that turns on the corti-
cotropin-releasing hormone (CRH), and cyclooxygenase-2
(COX-2) genes, in the placenta," explains Dr. Wang. The
increase in CRH and the prostaglandins produced by
COX-2 are important steps in the initiation of labor.
In other words--and no surprise to any woman who has
experienced labor--it's all about stress and hormones.
"
"I
f we can understand what drives typical labor
with a full-term pregnancy, then we may be able to
find a therapy to avoid or stop early labor and
prevent death or disabilities in infants as a result of
preterm birth," says Todd Rosen, MD, chief, division
of maternal-fetal medicine, Robert Wood Johnson
Medical School (facing page, center), with members
of his research team, Bingbing Wang, PhD,
assistant professor of obstetrics, gynecology,
and reproductive sciences (right) and
laboratory technician Natalia Parobchak.