The main focus of our research is the disease mechanism of disorders caused by mutations in the transcription factor p63. Mutations in p63 cause limb defects, cleft lip/palate and ectodermal dysplasia manifested in skin and other ectodermal related appendages. Patients with similar phenotypes of p63-associated diseases but without p63 mutations might have a mutation in the genes or regulatory elements controlled by p63. We have identified a genome-wide catalogue of p63-responsive regulatory elements and shown proof-of-principle that Split Hand/Foot Malformation and cleft lip/palate can both be caused by disruption of the regulatory elements.
We are dedicated to continue the effort in the identification of regulatory network controlled by p63 and in the application of this network in genetic studies and potential interventions that can benefit patients.
Epigenetic and chromatin regulators in intellectual disability
Another focus area is the role of epigenetic and chromatin regulators in intellectual disability. One of such regulators is the Euchromatic Histone Methyltransferase 1 (EHMT1). Mutations and deletions in EHMT1 cause Kleefstra Syndrome with severe intellectual disability as the major feature. Our effort to identify the gene network and pathways regulated by EHMT1 using the functional genomics approaches aims at understanding the disease mechanisms.
We have established human Induced Pluripotent Stem cells (hiPSC) as a model system, and will use iNeurons derived from these patient iPSCs to investigate the gene regulation and neuronal deficit.
This group aims to establish disease models using patient material and model organisms to identify regulatory networks and disease mechanisms in developmental disorders. Using genomics technology, we map the genome-wide atlas of disease-associated regulatory elements beyond the coding regions.
Our main aim is to achieve a greater understanding of the molecular mechanisms of disease. By integrating fundamental and clinical research, we obtain multifaceted knowledge of (patho)physiological processes.