Our group is conducting translational research to understand how pathogenic CTCF variants disrupt chromatin architecture, gene regulation, and development. We welcome collaborative efforts to accelerate knowledge of CTCF-related disorder (CRD).
Aims
• To define the molecular consequences of CTCF mutations on chromatin structure and gene expression.
• To investigate how distinct mutation types influence neurodevelopmental and systemic phenotypes.
• To provide robust preclinical models and datasets for the research and clinical community.
Methods
• Generation of CTCF variant mouse models, including prevalent clinically observed missense alleles.
• Patient-relevant variant modeling in pluripotent stem cell systems.
• Application of NGS-based molecular profiling, including:
o ChIP-seq for CTCF binding and chromatin states.
o RNA-seq for transcriptional changes.
o Hi-C to map 3D genome architecture.
Phenotyping
• Comprehensive lifespan phenotyping of CTCF-variant mice:
o Neurobehavioral testing
o Growth and organ system assessment
o Immune and metabolic profiling
o Ageing-related outcomes
Timeline
• Ongoing studies: 2023–2026.
• Molecular and phenotypic datasets will be made available for research use.
Expected Outcomes
• Mechanistic insights into CTCF dysfunction in CRD.
• Improved genotype-phenotype correlations.
• Identification of candidate biomarkers and therapeutic targets.
• Publicly shared preclinical models and data.
Contact
We welcome inquiries regarding:
• Variant prioritization for modelling
• Clinical data sharing to inform genotype-phenotype studies
• Collaborative opportunities
Contact: Emma Price (emma.price2@nih.gov)
CTCF