Only a small fraction of the genome is active at any one point. Much of the genome, such as transposable elements, need to be silenced at all times. We study epigenetic repressors, proteins which keep parts of the genome silent. One such epigenetic repressor is SMCHD1. In humans, mutations in SMCHD1 cause two distinct diseases with different timings of onset and affecting different tissues. Loss of function mutations in SMCHD1 are known to be part of the cause of a muscle degenerative disorder known as facioscapulohumeral muscular dystrophy (FSHD). Missense mutations in the extended ATPase domain cause Bosma arhinia microphthalmia syndrome (BAMS) where patients are born without a nose. We aim to understand how mutations in SMCHD1 cause different outcomes and develop therapeutic options for patients.
Craniofacial anomalies are amongst the most common birth defects, either in isolation, or as part of a syndrome. Using human cells and animal models, we study the two cell types that give rise to cells in the face, namely neural crest and cranial placodes. We aim to understand the genes and pathways involved in forming these lineages and what goes wrong in diseases affecting craniofacial development.
Rare genetic diseases
A rare disease is defined as one that affects less than 1 in 2000 people. While each rare disease is rare, together they affect 3-6% of the world’s population. We study rare genetic diseases to help provide genetic diagnosis for patients, discover the functions of new genes and learn about human development. We focus on congenital diseases, especially those affecting craniofacial and skeletal development. Once a new mutation is discovered, we can model the disease using patient-derived cells and animal models, to elucidate the disease mechanism.
Do you know someone with a rare genetic disease? We welcome collaborations with clinicians, scientists and patients.