Strong Laboratory Research Overview

We have identified loss of function variants in MED12 as causal for Hardikar syndrome, a multiple congenital anomaly syndrome that includes biliary dysgenesis. We are working to understand the mechanism by which MED12 modulates biliary tree development and why its deficiency causes biliary malformations. Our data suggests that MED12 affects ciliogenesis, ciliary signaling, and YAP signaling, all critical in biliary development, and we are working to elucidate the mechanism by which MED12 affects these diverse signaling pathways.

We have identified loss of function variants in MED12 as causal for Hardikar syndrome, a multiple congenital anomaly syndrome that includes global vascular malformations. We are exploring the role of MED12 in vascular development and the mechanism by which MED12 deficiency causes vascular anomalies in humans. We are also performing drug screens to identify pharmacological agents that ameliorate vascular disease in MED12 deficient animal models.

We have identified a specific variant in TOPORS as causal for the ciliopathies oral-facial-digital syndrome and Joubert syndrome. We are working to understand the mechanism by which TOPORS deficiency causes ciliopathy-spectrum disease.