Genome sequencing is transforming medicine, yet many patients still remain without a clear genetic diagnosis because candidate variants are difficult to interpret. Our group addresses this gap by generating experimental evidence that links genetic variation to cellular function and clinical phenotypes.

We work closely with Clinical Genetics, Genome Diagnostics, and other groups within the Department of Genetics at University Medical Center Utrecht to tackle unsolved cases and accelerate variant reclassification. We prioritize candidate variants using genetics and bioinformatics, model them with genome editing in relevant cellular systems, and measure their effects with molecular and cellular readouts.

Our research brings together three connected lines of work. First, we develop high-throughput functional assays, including multiplexed assays of variant effect, to resolve large numbers of variants of uncertain significance. Second, we study disorders caused by mutations in chromatin regulators, focusing on how these variants disrupt gene regulation and three-dimensional genome organization. Third, we investigate genetically unresolved primary ciliary dyskinesia by integrating genomics with functional testing in patient-derived airway models.

By building robust pipelines from variant prioritization to functional evidence and return of results, we aim to increase diagnostic yield, reduce uncertainty for families, and create a foundation for future targeted therapies.