About the Lab
Glycosylation is the most common post-translational modification of extracellular 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-glucose 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. We have reported a mouse model for a human developmental disorder called Alagille syndrome (ALGS), which is mostly caused by dominant mutations in the Notch pathway ligand JAG1. Our work suggests that Poglut1 is a dominant genetic suppressor of Jag1[+/-] phenotypes in mice. Part of our efforts is dedicated to understanding the mechanisms underlying Jag1 haploinsufficient phenotypes in mice and their suppression by decreasing Poglut1 levels. In another project, we are using Drosophila to understand the regulation of animal development by N-glycanase 1 (NGLY1), an enzyme mutated in a multisystem developmental disorder called NGLY1 deficiency. We hope that our findings will shed light on the pathophysiology of these human diseases and provide a framework to identify mechanism-based therapies for them.
See a list of projects for more details.