About the Lab
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.
View a list of projects for more details.
Recent News
- Duncan’s manuscript on a new therapeutic approach for Alagille syndrome liver disease was accepted by Gastroenterology.
- Yaniv presented a poster at the Digestive Disease Center Annual Symposium in Houston.
- Our lab presented three posters (Ashutosh, Soomin, and Yaniv) at the Annual Retreat of the Department of Molecular and Human Genetics
- We uploaded a preprint of Soomin's manuscript in collaboration with Paradas, Haltiwanger and Darabi groups to bioRxiv.
- Hamed was an invited speaker at the Annual Symposium of Sanford Center for Pediatric Research in Sioux Falls.
- Hamed gave a talk at the Notch Gordon Conference in Lewiston.
- Our R35 grant from NIGMS was renewed.
- Dr. Yaniv Faingelernt, a Pediatric Gastroenterologist from the Schneider Children's Medical Center in Israel, has joined our lab to work on mouse models of cholestatic disorders.
- Our lab presented a talk (Hamed) and three posters (Ashutosh, Soomin, and Duncan) at the Annual Retreat of the Department of Molecular and Human Genetics.
- Hamed presented our work at the 26th International Symposium on Glycoconjugates (Glyco26) in Taiwan.
- Ashutosh’s paper on the role of fly NGLY1 in gut permeability, innate immunity and lipid catabolism was accepted by Nature Communications.
- Nima and Hamed were co-authors on a paper from the Darabi lab in Molecular Therapy - Nucleic Acids on modeling a muscle disease using iPSCs.
