Associate Professor
Department of Molecular & Human Genetics
Genetics & Genomics Graduate Program
Baylor College of Medicine
Associate Professor
Program in Developmental Biology
Development, Disease Models & Therapeutics Graduate Program
Baylor College of Medicine


MD from Tehran University Of Medical Sciences
Post-Doctoral Fellowship at University Of Ottawa
Post-Doctoral Fellowship at Baylor College Of Medicine

Honors & Awards

Glycobiology Significant Achievement Award, Society for Glycobiology and Oxford University Press (2017)
Norton Rose Fulbright Faculty Excellence Award, BCM (2017)
Alagille Syndrome Accelerator Award, The Medical Foundation (2015)
Best Lecturer, 8-Stranded Beta-Barrel Jelly Roll Award, BCM (2014)
John S. Dunn Research Scholar, UT-Houston (2011)
Young Investigator Recognition Award, UT-Houston (2009)
Basil O'Connor Award, March of Dimes (2008)

Professional Interests

  • Biliary development and repair (Alagille syndrome)
  • Glycosylation and deglycosylation in developmental signaling
  • NGLY1 deficiency

Professional Statement

Glycosylation is the most common post-translational modification of extracellular and secreted proteins and plays major roles in various aspects of cellular and organismal biology. We use Drosophila and mouse genetics, cell culture experiments and biochemical assays (in collaboration) to understand the role of glycosylation and deglycosylation in animal development and pathophysiology of human disease. A major focus of our work is on glycosyltransferases that add O-glucose glycans to epidermal growth factor-like (EGF) repeats and their role in the regulation of the Notch signaling pathway. Another project focuses on a cytoplasmic enzyme called N-glycanase 1, mutations in which have recently been identified in a developmental disorder. We hope that our findings will shed light on the pathophysiology of the human diseases caused or modified by alterations in the function of these enzymes and will provide a framework to identify mechanism-based therapies for them.

Role of O-glucose glycans in animal development

An evolutionarily conserved enzyme called POGLUT1 (Rumi) adds an O-linked glucose to EGF repeats harboring a CXSX(P/A)C consensus motif. Several xylosyltransferases extend the O-glucose by adding one or two xylose residues to it. We have shown that O-glucose residues on the Notch receptor promote Drosophila Notch signaling in all contexts studied so far, but addition of xylose to O-glucose inhibits Notch signaling in specific contexts. We are examining the molecular mechanisms underlying the differential regulation of the Notch pathway by glucose versus xylose residues. Transgenic expression of human POGLUT1 rescues the rumi loss-of-function phenotypes in flies, and shRNA-mediated knock-down of Poglut1 in several mammalian cell lines results in decreased Notch signaling. However, given the lethality of Poglut1 mutant mice at mid-gestation, the in vivo role of POGLUT1 in various developmental contexts and the impact of O-glucose glycans on the activity of specific mammalian Notch receptors and ligands are not clear. We are using conditional loss-of-function studies and cell-based assays to understand the role of POGLUT1 in mammalian development and Notch signaling.

A mouse model for Alagille Syndrome

Alagille syndrome (ALGS) is an autosomal dominant disorder characterized by a congenital cholangiopathy of variable severity accompanied by cardiac, skeletal, renal and other abnormalities. In 94% of cases, ALGS is caused by mutations in JAG1, which encodes one of the ligands for the Notch pathway. We have recently reported a mouse model for the ALGS and have identified Poglut1 as a dominant genetic suppressor of the ALGS biliary phenotypes. Ongoing experiments are aimed at using this model to better understand the pathophysiology of ALGS and to develop a therapy for this disease.

A Drosophila model for NGLY1 deficiency

It has recently been reported that human patients with mutations in N-glycanase 1 exhibit a host of developmental abnormalities including a delay in physical and intellectual development, movement disorders and lack of tears. NGLY1 is a “deglycosylation” enzyme and is thought to remove N-linked glycans from glycoproteins destined for proteasomal degradation. However, the biologically-relevant targets of NGLY1 and the developmental processes sensitive to loss of its activity are not known. We are using Drosophila to understand the cellular and physiological defects caused by the loss of NGLY1 and to identify potential therapeutic targets for the disease. These studies are in collaboration with a group of researchers around the world who are using biochemical, cell biological, mouse genetics and systems biology approaches to understand the biology of NGLY1 and the pathophysiology of NGLY1 deficiency.

Selected Publications