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.
Recent News
- Our paper on the conserved role of NGLY1 in regulating AMPKα signaling was accepted by PLOS Genetics.
- Our paper on the direct regulation of BMP4 signaling by NGLY1 was accepted by eLife.
- Our new R01 grant of the role of POGLUT1 in muscle development and disease was funded (collaboration with Darabi, Haltiwanger and Paradas groups)
- Ashutosh Pandey and Nima Niknejad published a review article on Notch glycosylation in Glycobiology.
- We welcome Duncan Fox to the lab, our new Graduate Student from the Genetics & Genomics Program!
- Ashutosh Pandey and Hamed Jafar-Nejad were co-authors on a collaborative paper in Acta Neuropathologica on the identification of new muscular dystrophy patients with POGLUT1 mutations.
- Ashutosh Pandey published a paper (with Beth Harvey from Haltiwanger lab as co-first author) in Cell Reports on identification of critical Fringe and O-fut1 sites on Drosophila Notch.
- Josh Adams' review article on the roles of Notch signaling in liver development and disease was published in Biomolecules.
