Investigating SETBP1 pathogenic variants in lung malformation and function using human induced pluripotent stem cell-derived organoids

Awardee: Amy Wong

Institution: Toronto Hospital for Sick Children

Grant Amount: $70,000.00

Funding Period: February 1, 2025 - January 31, 2026

---

Summary:

Schinzel-Giedon Syndrome (SGS) is an ultra-rare, life-limiting multisystem disorder caused by mutations in the SETBP1 gene that results in abnormal accumulation of the protein. At the genetic level, SETBP1 helps regulate the expression of genes that drives developmental processes. Therefore disruption in how this protein functions can impact a wide spectrum of developmental programs leading to abnormalities including broad neurodevelopmental impairments, gastrointestinal complications and structural malformations in multiple organs, with no cure. Lung malformations and increased risk of respiratory infections is a clinical feature in some SGS patients, the mechanism of how SETBP1 impacts how the lung cells form and function is unknown. Here, we will create lung organoids (mini lungs in a dish) from stem cells harbouring SETBP1 pathogenic mutations to better understand how the protein impacts the formation of the airway cells and function of the airways including response to respiratory virus infections.