Constitutional activation of molecular signaling pathways that transduce growth factor stimuli leads to both vascular and pigment cell anomalies. In humans, these take the form of a wide variety of congenital malformations and cancers. Our group studies how these pathways impact differentiation of a multipotent progenitor population known as neural crest cells (NCC).
We are exploring how a limited number of mutations in key molecules contribute to such diverse pathologies as common arterial trunk, giant congenital melanocytic nevus, cleft palate, microphthalmia, arteriovenous malformations in the skin and head, but also under other circumstances to melanoma and neuroblastoma. A whole-genome approach in families with giant congenital melanocytic nevus is enabling us to analyze inherited, non-coding modifier elements that may affect outcomes. Current projects are to characterize and identify the effects of signal modulation in our animal models and primary cell cultures from embryos and affected patients, with the goal of developing novel therapeutic approaches to treating or curing a wide class of individually often rare diseases and associations.