Putting a Young Girl’s Plans into Action
”Less talk, more action,” was a common refrain for 10-year-old Gabriella Miller. Before she died from brain cancer in October 2013, Gabby pushed Congress to spend more money on children’s cancer research. In April 2014, less than six months later, Congress passed the Gabriella Miller Kids First Research Act. The law authorized funds for 10 years to the NIH Common Fund to support pediatric research.
But “pediatric research” is broad. NIH decided to develop a resource that would benefit cancer researchers and those studying structural birth defects, conditions that have profound effects on kids and their families. Because studies have suggested that babies born with birth defects are at a higher risk of developing childhood cancer, further analysis of this relationship would provide a fresh perspective.
Thus, the Gabriella Miller Kids First Pediatric Research Program began. Leadership of the program is shared across several NIH institutes, including the Eunice Kennedy Shriver National Institute of Child Health and Human Development, (NICHD), the National Cancer Institute, the National Heart, Lung, and Blood Institute, and the National Human Genome Research Institute. The mission is to develop tools and resources to better understand the relationship between specific structural birth defects, such as congenital heart defects, neural tube defects, and cleft palate, and a variety of childhood cancers.
NICHD has a long-standing research portfolio on birth defects and an overall focus on improving pediatric health. Lorette Javois, Ph.D., of NICHD’s Developmental Biology and Structural Variation Branch (DBSVB) chairs the Program’s Working Group. Javois believes the Kids First initiative provides a unique opportunity: By studying children born with birth defects who develop childhood cancer, researchers can attempt to understand what goes wrong in developing cells.
“As a developmental biologist, I’m very interested in understanding how the same genes and gene pathways involved in the formation of organs also continue to control normal cell growth later in life,” she said. “If there is a problem during development, why is there sometimes a problem later in childhood that leads to cancer?”
Developing a Data Bank
The main goal of Kids First is to create a large data bank that enables researchers to better study children with birth defects, cancer, or both. This resource will include thousands of biological samples as well as clinical data from children and their families who have agreed to participate in the research. The data bank will be accessible to researchers who work with children in the hospital, as well as those who work in laboratories doing basic research with animal models. All of the samples will be anonymous and confidential.
The biological samples and associated clinical data will help researchers determine which genetic pathways contribute to birth defects and cancers. Genes contribute to obvious physical differences, such as height or eye color. But, they also have more subtle effects. Examining changes in DNA will lead to clues about rare diseases or defects and potentially lead to better diagnoses and new methods of treatment and prevention.
The key to the resource data bank is its size. Bigger is better. Because birth defects and childhood cancers are relatively rare, researchers will need large numbers of samples. By the end of 2017, Javois expects the data resource bank to hold more than 15,000 specimens. Grantees interested in applying to have samples sequenced can submit applications by March 7th 2017, to submit applications.
“The larger the pool of data we collect, the more likely we are to find the genes causing the abnormalities,” she said.
Encouraging Research Collaboration
Once the data bank is in place, researchers can collaborate and compare findings. The Kids First initiative aims to bring together clinicians—who work with patients—and research scientists—who use animal models to study the conditions in the lab. These specialized professionals often don’t attend the same meetings or have an opportunity to collaborate.
“Some researchers are good at having a foot in both worlds—the basic research lab and the clinic,” said Javois. “But most don’t really interact that much. This resource is being designed for both to use, hopefully in a collaborative way, to maximize their collective expertise in addressing the problems of birth defects and pediatric cancers.”
In September 2017, the Gabriella Miller Kids First Working Group will host its first annual meeting for researchers and for all those receiving Kids First grants. The group will map out future goals and collaborations, including identifying research that is progressing well and areas that need greater focus or additional data.
In addition to leading the Kids First Working Group, Javois also heads the Trans-NIH Structural Birth Defects Working Group, which collaborates with Kids First. Its 11th Structural Birth Defects Meeting 
will be held in Bethesda April 3-5, 2017 and is open to anyone in the birth defects research community. The gathering is an opportunity to discuss, share, and collaborate on research activities and ideas.
NICHD’s Focus on Structural Birth Defects
Through DBSVB and other components, NICHD conducts and supports research projects on structural birth defects. Here are a few examples its work:
- Researchers found an association between exposure to certain air pollutants before or during the early months of pregnancy and cleft palate, a condition in which babies are born with a split in their top lip or in the roof of their mouth. (PMID 26099933)
- Heart defects are characteristic of the rare genetic disorder Cornelia de Lange Syndrome (CdLS). Using a mouse model of CdLS, researchers were able to track, for the first time, the way the gene responsible for CdLS interacted with specific cells as the heart developed. Their discovery could lead to preventative treatments for congenital heart defects. (PMID 27606604)
- Scientists created a model placenta, the organ that nourishes the fetus in the womb and also serves as a protective barrier from infection. The model could help researchers understand how some infections, like Zika virus, cross the barrier to cause birth defects. (PMID 26973875)
More Information
- Gabriella Miller Kids First Pediatric Research Program
- NICHD A-Z Topics
- Trans-NIH Structural Birth Defects Working Group
Originally Posted: January 26, 2017
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