Investigating long-range enhancers and 3D genome topology at a human craniofacial disease locus

Perturbation of gene regulation is central to many human genetic developmental disorders. In our lab, we study human facial development motivated by the wide diversity in facial appearance between individuals and the high frequency of birth malformations impacting the face. As our model, we focus on the SOX9 regulatory domain where non-coding mutations have been associated with facial dysmorphology. To explore mechanisms of disease, we leverage in vitro differentiation of facial progenitor (cranial neural crest) cells and have previously demonstrated that loss of extreme long-range enhancers (Long et al, 2020) and perturbation of 3D genome topology (Chen*, Long* et al, in preparation) can be implicated in human disease. There are a number of exciting projects available in the lab. In one project, we will further explore the role of local 3D chromosomal structure in gene regulation. To do so, we will leverage human embryonic stem cells coupled with genetic engineering, reporter assays, genomics, and chromosomal imaging to explore the role of novel structural features in gene regulation across craniofacial development at loci implicated in craniofacial disease.