Unlike other mutations that cause Cornelia de Lange Syndrome, little is known about SMC3 mutations as they only comprise of < 2% of the cases.
GOALS:
- Create SMC3-CdLS animal models (especially one that mimics the A485del mutation)
- Characterize the phenotype of a SMC3-CdLS animal model with respect to:
- Structural or functional abnormalities, including similarities or differences with existing NIPBL-animal models.
- Whether the causal SMC3 mutant allele behaves as a loss-of-function or gain-of-function allele, and the extent to which SMC3 is a haplosufficient gene.
- Molecular pathways that are dys-regulated in SMC3-CdLS (e.g. transcriptional abnormalities, disruptions of signaling pathways)
- Investigate therapeutic approaches that can potentially be borrowed and tested from other transcriptomopathies (e.g. gene editing, gene replacement, protein replacement, RNA editing, RNA trans-splicing, etc)
- Investigate the effects of pharmacological agents (e.g. HDAC inhibitors, WNT activators, etc) on SMC3-CdLS animals or cells.
- Identify relevant signals or pathways that could be affected by drugs.
- Identify cells in which genetic intervention (e.g., gene editing, antisense oligonucleotides, etc.) would need to be carried out to achieve therapeutic benefit.
- Use models of SMC3-CdLS for pre-clinical research to test potential pharmacological or genetic interventions (Anti-sense oligos, CRISPR etc)
Help us give HOPE
to Vihaan and other kids
affected by CdLS
