Investigating regulatory grammar for a disease-associated craniofacial enhancer

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) or perturbation of 3D genome topology (Chen, Long et al, 2023) impact expression of a human disease gene. There are many exciting projects available in the lab on the themes of gene regulation, development and human genetic disease. In one project we will explore how enhancer function is encoded in DNA (Jindal and Farley, 2021), focusing on a human disease enhancer that is ablated in patients with craniofacial malformation (Long et al, 2020), and where we have observed ancient hominin variants can drive increased regulatory activity (Uttley, Jüllig et al, 2025). This project will build our understanding of enhancer regulatory logic and in the future may help decipher non-coding patient mutations and mechanisms of disease.