Functional genomics for rare genetic diseases

Research aim

Improve diagnosis and lay groundwork for precision therapies for rare genetic diseases by turning genomic findings into experimentally validated functional evidence that can guide patient care.

About us

Genome sequencing is transforming medicine, but many patients still remain without a clear genetic diagnosis because candidate variants are hard to interpret. We address this gap by generating scalable, experimental evidence that links genetic changes to cellular function and clinical phenotypes.

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

Our research combines three connected lines of work: (1) high-throughput functional testing using multiplexed assays of variant effect to resolve large numbers of variants of uncertain significance; (2) functional genomics of disorders caused by mutations in chromatin regulators, focusing on how variants disrupt gene regulation and three-dimensional genome control; and (3) solving 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.