Glycosylation is one of the most common post-translational modifications of proteins and plays major roles in various aspects of cellular and organismal biology. We use Drosophila and mouse genetics and cell culture experiments to understand the contribution of glycosylation and deglycosylation to the regulation of animal development and pathophysiology of human disease.
A major focus of our work is on POGLUT1 and other glycosyltransferases responsible for the addition of O-linked glycans to epidermal growth factor-like (EGF) repeats. Specifically, we would like to understand how these glycosyltransferases regulate the activity of the Notch signaling pathway in a dosage-sensitive and tissue-specific manner.
We have reported a mouse model for Alagille syndrome (ALGS), a multisystem disorder, which predominantly affects bile duct development and is mostly caused by haploinsufficiency of the Notch pathway ligand JAG1. We have identified a number of dosage-sensitive modifiers of ALGS phenotypes in mice (including Poglut1) and are characterizing their role in biliary development, in hopes of identifying a mechanism-based therapy for ALGS.
In another project, we are using Drosophila and mice to study N-glycanase 1 (NGLY1), a deglycosylation enzyme mutated in a multisystem developmental disorder called NGLY1 deficiency.
See a list of projects for more details.