IPRD funded research by Yue (Julia) Wang

Congenital hyperinsulinemia is a rare and deadly pediatric disease with an estimated incidence of 1 in 25,000 to 1 in 50,000 births and as high as 1 in 2500 births in consanguineous societies. This disease is often manifested in the neonatal and infant stages. Affected individuals have persistent and dangerously low blood glucose and high insulin levels. The latter further inhibit ketogenesis, lipolysis, and other fuel mobilization processes depleting all energy sources for the brain placing the young patients at extremely high risk of permanent brain damage and long-term neurological complications. Mutations in more than 12 genes, all critical for secretion of insulin from the pancreatic beta cells, are associated with the disease. However, the causative mutations for more than half of the cases are unknown. Furthermore, there is limited understanding on the genotype-phenotype correlations, including the relationship between genetic variants and drug sensitivities. This research project will establish a genomic pipeline to identify structural variants in candidate genes and design targeted genetic panels enabling rapid diagnosis and drug screening.

 

Resources

• Children's Hospital of Philadelphia
• Congenital Hyperinsulinemia International
• National Organization for Rare Disorders

IPRD-supported researcher Julia Wang, Ph.D., Assistant Professor of Biomedical Sciences at the Florida State University College of Medicine, is investigating congenital hyperinsulinism, a rare pediatric disorder characterized by excessive insulin secretion. This condition can cause dangerously low blood sugar levels, leading to seizures, brain injury, or even death. Current treatment options are limited, often relying on trial-and-error medication regimens and, in severe cases, surgical removal of pancreatic tissue.

Wang’s laboratory aims to transform this approach by applying functional genomics and CRISPR-based tools to connect specific genetic mutations with individual treatment responses. With support from research assistants Carson Mickey, Pilar Toledo, and Pamela Sandoval Sanchez, the team seeks to identify effective, tailored therapies for each patient. IPRD Director Pradeep Bhide noted that this research paves the way toward personalized precision medicine and improved outcomes for children affected by this devastating disorder.