Craniofacial Biobank Provides Clues to Causation

How can an in-house biobank unlock clues to the genetic variants underlying craniofacial conditions?

The Craniofacial Program at Children’s Hospital Colorado sees 400 patients annually, boasting some of the highest volumes nationwide. Although these conditions, such as cleft palate and craniosynostosis, are not rare, they are notorious for their variation in physical presentation. This makes it difficult for providers and researchers to draw conclusions about the genetic variations driving these diseases. University of Colorado senior researcher Cristan Carter is teaming up with Antonio Porras, PhD, Director of Research in the Department of Pediatric Plastic and Reconstructive Surgery, and Brooke French, MD, Co-Director of the Craniofacial Program, to create a repository that will not only uncover these missing links of causation — but also key routes to treating them.

In the past two decades alone, myriad areas of pediatric care have become more targeted thanks to advancements in genetic testing and precision medicine. But for craniofacial researchers, genetics knowledge specific to their field has remained elusive. “We don’t know the causes for the pathology in 80% to 90% of these children,” Dr. Porras says. “That’s a very big deal because you cannot really move toward personalized medicine if you don’t fully understand what is causing the disease in the first place.”

The barriers preventing more precise treatment of pediatric craniofacial conditions range far and wide. From a research perspective, investigations on craniofacial conditions have been meager, as there aren’t many clinics with high enough volumes to conduct significant patient cohort studies. Funding has also been scarce, making it hard to get research projects off the ground.

With few children to study and even fewer financial opportunities to go around, the landscape for genetic research on pediatric craniofacial conditions has been difficult, but it’s also been even further impeded by human nature itself. “These children grow very fast and look very different at different ages, so it’s very hard to identify common abnormal patterns between children that are at different stages of development,” Dr. Porras says.

Building a biobank

More than 30 years ago, the Craniofacial Program at Children’s Colorado became one of the first centers focused on multidisciplinary care and long-term treatment. The program grew in scale and scope over time, attracting more patients and specialty providers while expanding its data science research capabilities.

This created the perfect environment for conducting the kind of genetic research that had rarely been performed on craniofacial conditions. In 2020, Carter and Drs. Porras and French stepped in to realize this vision. “We saw a unique opportunity because we had high enough volumes to consider creating a biobank and putting data together that will start giving answers to these questions,” Dr. Porras says. “We have become one of the national leaders in data science research for craniofacial conditions. The only thing missing was the link with genetics.”

Under the leadership of Dr. French, who served as principal investigator, Carter executed all the steps needed to create an in-house biobank, which included everything from institutional review board approval paperwork to the logistics of how to store and process tissue samples. The team began collecting blood and affected bone and cartilage in March of 2023, and now gives each patient and family the option to join the research project. After tissue has been collected, Carter extracts cells containing genetic material and takes the sample to the lab — a space lent to the team by University of Colorado School of Medicine medical genetics researcher Tamim Shaikh, PhD. There, research teams can perform a combination of different analyses, from genomic sequencing to changes in RNA and protein expression levels.

“The idea is that once we can process all this information, we actually have a database of not only tissue samples, but also genetic information, which can be used infinitely,” Carter says.

A foundation for craniofacial research

Unlike traditional science research projects in pediatrics, which receive funding from the National Institutes of Health, the biobank is fully supported by the Center for Children’s Surgery at the University of Colorado Anschutz Medical Campus. The center’s Director of Operations, Sandra Talley, played an important role in ideating the project and bringing the biobank to life. Plus, this is a strategic partnership because patients visiting the Craniofacial Program benefit from a multidisciplinary care approach that often includes surgery.

“Our surgical interventions are already more personalized than anywhere else in the country right now, but with treatments more targeted to the specific causes of diseases, we can take a multi-perspective, personalized approach that addresses or treats every patient differently depending on what exactly their condition is,” Dr. Porras says.

With this support, the researchers hope the biobank can serve as a hub for other craniofacial researchers, as it is not just limited to studies on craniosynostosis — its initial pilot research project. In turn, the biobank’s creators hope that these collaborations and the findings that result will bring notoriety and resources back to their project. “Because the Center for Children’s Surgery has been kind enough to fund this data collection program, we’re hoping that basic scientists now are able to leverage the biobank by doing their investigations in partnership with us,” Dr. Porras explains.

French points out that the team encourages other investigators to submit their ideas for new areas of research in craniofacial conditions and hopes this will expand the capacity and benefits of the biobank they worked so hard to create.

“We are excited to explore opportunities with colleagues to diversify and broaden applications through the craniofacial biobank,” French says. “This is an incredible time to deepen our understanding and improve the care of children with craniofacial differences.”