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Charleston, SC 29425
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January 2008
Children's Research Institute News Brief
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Bernard L. Maria, MD, MBA
Executive Director
Darby Children's
Research Inst. |
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Inderjit Singh, PhD
Scientific Director
Darby Children's
Research Inst. |
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New research could be a start for early diagnosis of congenital birth defects
Dr. Ed Krug expects his research may ultimately lead to a blood test that provides early diagnosis of congenital heart defects.
In his lab in the DCRI, Dr. Krug, of the Department of Cell Biology and Anatomy, is developing new technology to determine how the valves and septa (internal partitions) of the heart are formed, and under what conditions they might be altered.
"Valvuloseptal defects are a significant problem, occurring in approximately one out of 10,000 live births," says Dr. Krug.
If the heart lacks the correct separation of chambers and proper "plumbing," oxygenated and deoxygenated blood are mixed, resulting in what is commonly called a blue baby.
Though many of these congenital defects can be corrected surgically, Dr. Krug hopes his research will provide the foundation for a discovery that will allow clinicians to detect abnormal patterns of protein expression in the developing heart long before the structural defects become apparent, offering the potential for non-surgical intervention.
He and other DCRI researchers are looking at protein changes during the critical period that occurs just two to four weeks after fertilization. "The heart is the first organ system to form in an embryo, and if development within this brief window doesn't go properly, most likely the embryo is not going to survive."
It's detailed and intricate work: at this embryonic stage, the heart is smaller than the head of a pin. Dr. Krug works with chicken and mouse embryos, which are excellent models of human heart development.
His lab is looking at the impact of physical and nutritional environments, including the effects of trichlor-ethylene (a major contaminant found at Superfund hazardous waste sites, where women experience high rates of infertility and miscarriage) and low levels of alcohol. "Our results show that very early in development, these conditions have an effect on the formation of the cells that become components of the valves and septa of the heart," he notes.
Lots of researchers are studying protein changes in embryos, but what's different about his research is a novel use of MALDI-TOF mass spectrometry, says Dr. Krug: "This technology allows us to characterize individual phases of early heart development that differ by as little as two hours."
Developed in conjunction with Dr. Kevin Schey in the Department of Pharmacology and Dr. John Schwacke in the Department of Biostatistics, Bioinformatics and Epidemiology, the new application came out of the Cardiovascular Proteomic Center at MUSC, funded by a seven-year, $15.3 million contract awarded by the National Heart, Lung and Blood Institute in 2002. It's one of just ten such centers in the US.
"The application of MALDI-TOF is exciting because it's an inexpensive and rapid methodology that determines changes in protein expression in minute amounts of tissue. It gives us new potential for studying the mechanisms of early heart development towards identifying factors that might lead to congenital abnormalities or spontaneous miscarriages."
It's technology that he hopes will lead, simply, to more research, to more information that will help interpret more experiments. "To really understand what affects heart development, researchers must be able to detect subtle differences over short intervals of time and at high sensitivity - in a highly reproducible manner," he notes.
Dr. Krug believes his is a jumping-off point that could result in genetic screenings and susceptibility issues that offer better predictability.
"The way we analyze congenital defects now is structurally - that is, after they have occurred," he says. "If we can ultimately pick up changes in protein expression that predict changes later on, a physician could alert the expectant mother to potential problems and perhaps circumvent their occurrence with medication and altered lifestyle choices."
The potential? Reducing congenital heart defects, and possibly even early diagnosis. "Those are really far out, because a lot more work remains to be done," says Dr. Krug. "But you build from the foundation up."
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