Email

hamedj@bcm.edu

Positions

Professor

Department of Molecular & Human Genetics
Baylor College of Medicine

Professor

Genetics & Genomics Graduate Program
Baylor College of Medicine

Professor

Program in Developmental Biology
Development, Disease Models & Therapeutics Graduate Program
Baylor College of Medicine

Education

MD from Tehran University Of Medical Sciences

06/1994 - Tehran, Iran

Post-Doctoral Fellowship at University Of Ottawa

03/2000 - Ottawa, Ontario Canada

Post-Doctoral Fellowship at Baylor College Of Medicine

12/2006 - Houston, Texas United States

Honors & Awards

Harrington Scholar-Innovator Award, Harrington Discovery Institute (2025)

Alagille Syndrome Accelerator Award, The Medical Foundation (2019)

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

The long-term goals of our research are (1) to understand the roles of glycosylation and deglycosylation in the regulation of developmental signaling pathways, animal development, and human disease pathophysiology, and (2) to identify and characterize dosage-sensitive genetic modifiers of select human rare diseases in animal models, followed by establishing the most promising candidates as potential therapeutic targets for those diseases. A long-term area of interest has been the role of O-linked glycosylation in animal development and human disease. Our efforts in this area have led to the identification of the glycosyltransferase POGLUT1, which adds O-glucose glycans to epidermal growth factor-like (EGF) repeats of the receptors and ligands of the Notch signaling pathway, and characterization of this enzyme and its downstream glycosyltransferases in Notch signaling. More recently, we and our collaborators have identified a new form of limb-girdle muscular dystrophy caused by recessive mutations in POGLUT1 and have elucidated the roles that this enzyme plays in the generation and maintenance of muscle stem cells.

A major focus of our group over the last decade has been the development of the biliary system in the context of Alagille syndrome (ALGS), a multisystem disorder characterized by bile duct paucity and primarily caused by mutations in the Notch pathway ligand JAG1. Alarmingly, only 24-40% of patients with ALGS with early cholestasis reach their 18th birthday without a liver transplant. Coexisting cardiovascular and renal anomalies often preclude liver transplantation in ALGS, and even among transplant recipients, complications are common. Currently, no FDA-approved therapies exist to promote biliary development in ALGS or other diseases with bile duct paucity. To address this unmet need, we have developed mouse models that span the spectrum of ALGS liver disease severity. Through genetic studies, we identified two dosage-sensitive suppressors of the liver phenotypes in these models: the glycosyltransferase Poglut1 and the transcription factor Sox4. We have reported that postnatal knockdown of these genes—via antisense oligonucleotides for Poglut1 and adeno-associated virus for Sox4—dramatically improves liver phenotypes in ALGS models. Ongoing work includes mechanistic and preclinical studies aimed at advancing these candidates toward clinical trials, as well as exploring their relevance to other cholestatic diseases.

We are also investigating the role of N-linked glycosylation and deglycosylation in animal development, with a focus on intestinal development, innate immunity, and metabolism. Using Drosophila as a model, we found that loss of the deglycosylating enzyme NGLY1 disrupts gut barrier integrity, triggers innate immune activation, and induces severe lipid catabolism. Our data suggest that altered gut microbiome contributes to the developmental delay in Ngly1-mutant Drosophila larvae. Current efforts focus on determining the molecular basis and the physiological consequences of altered gut microbiome in Ngly1-deficienct Drosophila and in mutants for select N-glycosylation pathway components. We are also examining the consequences of loss of these genes in the intestine on other organs, including the fat body (equivalent to mammalian liver and immune system) and the nervous system. These studies aim to uncover shared and distinct roles of glycosylation-related genes in shaping the gut microbiome and modulating the host’s response to it, as well as inter-organ communication. Ultimately, this work may provide novel insight into the pathophysiology of congenital disorders of glycosylation and deglycosylation.

Websites

Selected Publications

• Galeone A*,#, Solazzo E*, Lavezzari F, Han SY, My B, Rizzo R, Gigli G, Jafar-Nejad H# and Vaccari T# "TUSC3 serves as a rate-limiting gatekeeper of a glycan-mediated ER Triage Checkpoint for BMP4/Dpp." bioRxiv. 2025;
• Cho S*, Servián-Morilla E*, Garrido VN, Rodriguez-Gonzalez B, Yuan Y, Cano R, Rambhiya AA, Darabi R, Haltiwanger RS, Paradas C#, Jafar-Nejad H# "The glycosyltransferase POGLUT1 regulates muscle stem cell development and maintenance in mice." PLOS Genetics. 2025 Aug 18;21(8):e1011806. Pubmed PMID: 40825068
• Fox D, Xie J, Burwinkel JL, Adams JM, Chetal K, Keivandarian M, Faingelernt Y, Subramanian S, Lopez MF, Salomonis N, Zarrin-Khameh N, Gao G, Huppert SS and Jafar-Nejad H "AAV-mediated silencing of Sox4 leads to long-term amelioration of liver phenotypes in mouse models of Alagille syndrome." Gastroenterology. 2025 Oct;169(5):1000-1016. Pubmed PMID: 40446945
• Pandey A, Galeone A, Han SY, Story BA, Consonni G, Mueller WF, Steinmetz LM, Vaccari T and Jafar-Nejad H "Gut barrier defects, intestinal immune hyperactivation and enhanced lipid catabolism drive lethality in NGLY1-deficient Drosophila." Nature Communications. 2023 Sep;14:5667. Pubmed PMID: 37704604