We are interested in the structural aspects of components of the Hedgehog pathway that generate the diversity of cellular responses to the Hedgehog ligands in normal cells, during mammary gland development and in transformed (cancer) cells.
We have had a long-standing interest in studying the role and activities of the essential developmental pathway, the Hedgehog pathway, during mammary gland development. This has lead us to work in two interacting areas.
The first is to understand how Hedgehog-signalling contributes to morphogenesis of the mammary gland during puberty. In this context we are interested further in understanding how this same pathway interacts with other signalling pathways that give rise to cancer in the mammary gland.
This focus stems from a second line of investigation in which we are defining the structural aspects of the receptor of the Hedgehog ligands, called Pathced-1, that give rise to its activities. In particular, we are defining novel pathways that are stimulated by the Hedgehog ligands due to the interaction of components of these alternative pathways to the unique cytoplasmic region of Patched-1 predicted to form an Intrinsically Disordered Protein Region.
As a final area of investigation, we have begun a collaboration with a number of labs that are defining the role of a related protein, called PtchD1, that plays a role in Autism Spectrum Disorder (ASD) and ADHD. These investigations will define the activities of PtchD1 and how, upon their mutation in humans, ASD/ADHD arises.