UNMC to Lead $5.6 Million Research Project Looking Into Causes of Congenital Heart Defects

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.