A5021045099- Glycosylation and Glycoproteins Research
- Carbohydrate Chemistry and Synthesis
- Lysosomal Storage Disorders Research
- Myeloproliferative Neoplasms: Diagnosis and Treatment
- Autoimmune and Inflammatory Disorders
- Galectins and Cancer Biology
- Pancreatic function and diabetes
- Eosinophilic Disorders and Syndromes
- Genomics and Rare Diseases
- Cellular transport and secretion
- Genetics and Neurodevelopmental Disorders
- Biochemical and Molecular Research
- Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis
- Ubiquitin and proteasome pathways
- Cancer Research and Treatments
- Genomic variations and chromosomal abnormalities
- RNA modifications and cancer
- Metabolism and Genetic Disorders
- Connective tissue disorders research
- Amino Acid Enzymes and Metabolism
- Infant Nutrition and Health
- Chromosomal and Genetic Variations
- Congenital limb and hand anomalies
- Endoplasmic Reticulum Stress and Disease
- Ion Transport and Channel Regulation
Discovery Institute
2015-2024
Sanford Burnham Prebys Medical Discovery Institute
2015-2024
Nationwide Children's Hospital
2021
The Ohio State University
2021
Washington Center
2015-2016
University of Washington
2015-2016
Children's Memorial Health Institute
2014
Duke University
2012
Torrey Pines Institute For Molecular Studies
2010
Institute for Medical Research
2007-2009
Congenital disorders of glycosylation are genetic syndromes that result in impaired glycoprotein production. We evaluated patients who had a novel recessive disorder glycosylation, with range clinical manifestations included hepatopathy, bifid uvula, malignant hyperthermia, hypogonadotropic hypogonadism, growth retardation, hypoglycemia, myopathy, dilated cardiomyopathy, and cardiac arrest.Homozygosity mapping followed by whole-exome sequencing was used to identify mutation the gene for...
Abstract In eukaryotic cells, one-third of all proteins must be transported across or inserted into the endoplasmic reticulum (ER) membrane by ER protein translocon. The translocon-associated (TRAP) complex is an integral component translocon, assisting Sec61 protein-conducting channel regulating signal sequence and transmembrane helix insertion in a substrate-dependent manner. Here we use cryo-electron tomography (CET) to study structure native translocon evolutionarily divergent organisms...
We describe a new Type II congenital disorder of glycosylation (CDG-II) caused by mutations in the conserved oligomeric Golgi (COG) complex gene, COG8. The patient has severe psychomotor retardation, seizures, failure to thrive and intolerance wheat dairy products. Analysis serum transferrin total N-glycans showed normal addition one sialic acid, but deficiency subsequent sialylation mostly N-glycans. Patient fibroblasts were deficient both N- O-glycans, also slower brefeldin A (BFA)-induced...
Cerebellar hypoplasia and slowly progressive ophthalmological symptoms are common features in patients with congenital disorders of glycosylation type I. In a group I unknown aetiology, we have previously described distinct phenotype severe, early visual impairment variable eye malformations, including optic nerve hypoplasia, retinal coloboma, cataract glaucoma. Some the overlapped other subtypes, such as vermis anaemia, ichtyosiform dermatitis, liver dysfunction coagulation abnormalities....
We describe two unreported types of congenital disorders glycosylation (CDG) which are caused by mutations in different isoforms the catalytic subunit oligosaccharyltransferase (OST). Each isoform is encoded a gene (STT3A or STT3B), resides OST complex and has distinct donor acceptor substrate specificities with partially overlapping functions N-glycosylation. The cases from unrelated consanguineous families both show neurologic abnormalities, hypotonia, intellectual disability, failure to...
In mitochondria, carbamoyl-phosphate synthetase 1 activity produces carbamoyl phosphate for urea synthesis, and deficiency results in hyperammonemia. Cytoplasmic 2, however, is part of a tri-functional enzyme encoded by CAD; no human disease has been attributed to this gene. The contains 2 (CPS2), aspartate transcarbamylase (ATCase) dihydroorotase (DHOase) activities, which comprise the first three six reactions required de novo pyrimidine biosynthesis. Here we characterize an individual who...
Pathogenic de novo variants in the X-linked gene SLC35A2 encoding major Golgi-localized UDP-galactose transporter required for proper protein and lipid glycosylation cause a rare type of congenital disorder known as SLC35A2-congenital disorders (CDG; formerly CDG-IIm). To date, 29 unique from 32 unrelated individuals have been described literature. The majority affected are primarily characterized by varying degrees neurological impairments with or without skeletal abnormalities....
Sirt1 is an NAD+-dependent deacetylase that plays a role in cellular processes such as transcriptional regulation, stress response, longevity and apoptosis. deacetylates histone proteins certain transcription factors p53, CTIP2 (chicken ovalbumin upstream promoter-transcription factor-interacting protein 2), FOXO (forkhead box O) NF-κB (nuclear factor κB). To identify potential Sirt1-interacting factors, we performed yeast two-hybrid screen. The screen identified TLE1 (transducin-like...
Nearly 50 congenital disorders of glycosylation (CDG) are known, but many patients biochemically diagnosed with CDG do not have mutations in known genes. Here, we describe a 16-year-old male who was born microcephaly, developed intellectual disability, gastroesophageal reflux and seizure disorder. We identified de novo variant the X-linked SSR4 gene which encodes protein heterotetrameric translocon-associated (TRAP) complex. The c.316delT causes p.F106Sfs*53 also reduces expression other...
Abstract BACKGROUND Primary deficiencies in mannosylation of N-glycans are seen a majority patients with congenital disorders glycosylation (CDG). We report the discovery series novel sera, plasma, and cultured skin fibroblasts from CDG having deficient mannosylation. METHOD used LC-MS/MS MALDI-TOF-MS analysis to identify quantify N-linked tetrasaccharide linked protein core, an N-tetrasaccharide (Neu5Acα2,6Galβ1,4-GlcNAcβ1,4GlcNAc) serum glycoproteins, fibroblast lysate caused by ALG1 [ALG1...