The University of Nebraska Medical Center has received a five-year,
$5.6-million federal grant to study the causes of congenital heart defects.
The grant called a program project grant was awarded by the National
Heart, Lung and Blood Institute, one of the institutes that comprise the
National Institutes of Health in Bethesda, Md. Thomas Rosenquist, Ph.D.,
interim vice chancellor for research at UNMC, is the principal investigator
of the grant.
Were optimistic that at the end of these five years, well be able
to make some predictions about congenital defects, and with prediction,
the possibility of prevention, said Dr. Rosenquist, who also is the vonHousen
professor and chairman of the department of cell biology and anatomy at
UNMC.
Program project grants are significant because they typically are significantly
larger than grants awarded to individual scientists, as they bring together
groups of researchers who use different methods to study a highly specific,
unified hypothesis. The grants are extremely competitive.
During the duration of this five-year grant, three teams of scientists
will investigate the way that selected genes may interact with certain
drugs, environmental exposures and vitamin deficiencies to cause abnormal
heart development.
This is the first NIH-funded program project that will test a unifying
hypothesis for this type of gene/environment interaction. Our hypothesis
is that these birth defects all have a common, fundamental cause, Dr.
Rosenquist said. At present, it is impossible to predict the probability
that birth defects will occur, based on genetic makeup or environmental
exposures. Were hoping to find some answers, so that these birth defects
can be prevented.
The three groups of investigators will consist of Dr. Rosenquists team,
which will utilize chicken embryos as their experimental model; a team
that includes Richard Finnell, Ph.D., director of Texas A&M Universitys
Institute of Biosciences and Technology, and Janee Gelineau-van Waes, DVM,
Ph.D., UNMC assistant professor of cell biology and anatomy, which will
study mice that have undergone genetic engineering to change their susceptibility
to congenital defects; and a team led by Gary Shaw, Ph.D., and Ed Lammer,
M.D., of the California Birth Defects Monitoring Project, which will study
congenital heart defects in human babies and the relationship that those
defects may have to the genetics and pre-natal behaviors of their mothers.
For several years, research has shown that a moderate intake of folic
acid during a mothers pregnancy decreases the risk of birth defects. In
this study, Dr. Rosenquist said, investigators will look at the way folic
acid helps prevent heart defects and how a deficiency of the vitamin may
interact with drugs such as alcohol or certain kinds of cough medicine
to increase the chances that a baby might have a heart defect.
Over the past few years, Dr. Rosenquists laboratories have developed
the idea that specific kinds of receptors in developing embryos may respond
to a large array of environmental exposures that previously hadnt been
recognized as having anything in common. Those may include a variety of
recreational and therapeutic drugs, as well as environmental exposures
including certain kinds of air and water pollution.
Using this grant money, Dr. Shaw will take what has been learned in
the animal labs of Dr. Rosenquist and Dr. Finnell and apply it to human
mothers and babies. As well, hell seek other genes and environmental exposures
that may be linked to increased probabilities of birth defects.
Well go back and test our animal models if he finds something in the
humans that might indicate a environment/gene relationship that may cause
a birth defect, Dr. Rosenquist said.
Dr. Shaws project will be the largest study every undertaken to determine
the relationship among heart defects, drugs, environmental exposures and
vitamin deficiencies in human babies.
Congenital heart defects are the most common birth defect and are the
top cause of death from birth defects during the first year of life, according
to the American Heart Association. Out of 1,000 births, eight babies will
have some form of congenital heart disorder. About 35,000 babies are born
with a defect each year. Charges for care exceed $2.2 billion annually,
for inpatient surgery alone.
This research could mean a tremendous amount for a lot of families,
both emotionally and financially, Dr. Rosenquist said. Were interested
in finding answers that will help children be at their playful, spirited
best.