A5027546016- Glycogen Storage Diseases and Myoclonus
- Genetics and Neurodevelopmental Disorders
- Retinal Development and Disorders
- Lysosomal Storage Disorders Research
- Photoreceptor and optogenetics research
- Retinal Diseases and Treatments
- Autoimmune Neurological Disorders and Treatments
- Carbohydrate Chemistry and Synthesis
- Blood disorders and treatments
- Vitamin C and Antioxidants Research
- Amino Acid Enzymes and Metabolism
- Pancreatic function and diabetes
- Retinoids in leukemia and cellular processes
- Diagnosis and Treatment of Venous Diseases
- Folate and B Vitamins Research
- Erythrocyte Function and Pathophysiology
- Metabolism and Genetic Disorders
- Cardiac Structural Anomalies and Repair
- Vasculitis and related conditions
- Mitochondrial Function and Pathology
- Monoclonal and Polyclonal Antibodies Research
- Platelet Disorders and Treatments
- interferon and immune responses
- Ovarian cancer diagnosis and treatment
- Biomedical Research and Pathophysiology
Eunice Kennedy Shriver National Institute of Child Health and Human Development
2013-2024
National Institutes of Health
2013-2024
Beam Therapeutics (United States)
2024
University of California, San Francisco
2023
Broad Center
2023
Blueprint Genetics (Finland)
2023
Foundation Fighting Blindness
2012-2021
University of California, San Diego
2019
Institut thématique Génétique, génomique et bioinformatique
2011
Health and Human Development (2HD) Research Network
2008
SummaryGlycogen-storage disease type 1 (GSD-1), also known as "von Gierke disease," is caused by a deficiency in microsomal glucose-6-phosphatase (G6Pase) activity. There are four distinct subgroups of this autosomal recessive disorder: 1a, 1b, 1c, and 1d. All share the same clinical manifestations, which abnormalities metabolism glucose-6-phosphate (G6P). However, only GSD-1b patients suffer infectious complications, due to both heritable neutropenia functional deficiencies neutrophils...
Neutropenia and neutrophil dysfunction are common in many diseases, although their etiology is often unclear. Previous views held that there was a single ER enzyme, glucose-6-phosphatase–α (G6Pase-α), whose activity — limited to the liver, kidney, intestine solely responsible for final stages of gluconeogenesis glycogenolysis, which glucose-6-phosphate (G6P) hydrolyzed glucose release blood. Recently, we characterized second G6Pase activity, G6Pase-β (also known as G6PC), also capable...
A deficiency in glucose-6-phosphatase-α (G6Pase-α) glycogen storage disease type Ia (GSD-Ia) leads to impaired glucose homeostasis and metabolic manifestations including hepatomegaly caused by increased neutral fat accumulation. recent report showed that G6Pase-α causes impairment autophagy, a recycling process important for cellular metabolism. However, the molecular mechanism underlying defective autophagy is unclear. Here we show mice, liver-specific knockout of (L-G6pc-/-) downregulation...
Abstract Ovarian cancer is the deadliest gynecologic in United States. When detected early, 5-year survival rate 92%, although most cases remain undetected until late stages where rates are 30%. Serum biomarkers may hold promise. Although many markers have been proposed and multivariate diagnostic models were built to fit data on small, disparate sample sets, there has no systematic evaluation of these a single, large, well-defined set. To address this, we evaluated dysregulation 204...
Glycogen storage disease type Ia (GSD-Ia) patients deficient in glucose-6-phosphatase-α (G6Pase-α or G6PC) manifest disturbed glucose homeostasis. We examined the efficacy of liver G6Pase-α delivery mediated by AAV-GPE, an adeno-associated virus (AAV) serotype 8 vector expressing human directed G6PC promoter/enhancer (GPE), and compared it to AAV-CBA, that murine expression using a hybrid chicken β-actin (CBA) promoter/cytomegalovirus (CMV) enhancer. The AAV-GPE hepatic infused G6pc−/− mice...
Blood glucose homeostasis between meals depends upon production of within the endoplasmic reticulum (ER) liver and kidney by hydrolysis glucose-6-phosphate (G6P) into phosphate (Pi). This reaction on coupling G6P transporter (G6PT) with glucose-6-phosphatase-α (G6Pase-α). Only one G6PT, also known as SLC37A4, has been characterized, it acts a Pi-linked antiporter. The other three SLC37 family members, predicted to be sugar-phosphate:Pi exchangers, have not characterized functionally. Using...
Glycogen storage disease type Ia (GSD-Ia), which is characterized by impaired glucose homeostasis and chronic risk of hepatocellular adenoma (HCA), caused deficiencies in the endoplasmic reticulum (ER)-associated glucose-6-phosphatase-α (G6Pase-α or G6PC) that hydrolyzes glucose-6-phosphate (G6P) to glucose. G6Pase-α activity depends on G6P transporter (G6PT) translocates from cytoplasm into ER lumen. The functional coupling G6PT maintains interprandial homeostasis. We have shown previously...
The photoreceptor outer segment is a highly specialized primary cilium that essential for phototransduction and vision. Biallelic pathogenic variants in the cilia-associated gene CEP290 cause non-syndromic Leber congenital amaurosis 10 (LCA10) syndromic diseases, where retina also affected. While RNA antisense oligonucleotides editing are potential treatment options common deep intronic variant c.2991+1655A>G CEP290, there need variant-independent approaches could be applied to broader...
A fine control of the blood glucose level is essential to avoid hyper- or hypo-glycemic shocks associated with many metabolic disorders, including diabetes mellitus and type I glycogen storage disease. Between meals, primary source gluconeogenesis glycogenolysis. In final step both pathways, glucose-6-phosphate (G6P) hydrolyzed by glucose-6-phosphatase (G6Pase) complex. Because G6Pase (renamed G6Pase-α) primarily expressed only in liver, kidney, intestine, it has implied that most other...
As bacteria grow and proliferate, they release a variety of volatile compounds that can be profiled used for speciation, providing an approach amenable to disease diagnosis through quick analysis clinical cultures as well patient breath analysis. practical alternative mass spectrometry detection whole cell pyrolysis approaches, we have developed methodology involves via sensitive, micromachined differential mobility spectrometer (microDMx), sampling headspace gases produced by growing in...
Glucose is absolutely essential for the survival and function of brain. In our current understanding, there no endogenous glucose production in brain, it totally dependent upon blood glucose. This generated between meals by hydrolysis glucose-6-phosphate (Glc-6-P) liver kidney. Recently, we reported a ubiquitously expressed Glc-6-P hydrolase, glucose-6-phosphatase-β (Glc-6-Pase-β), that can couple with transporter to hydrolyze terminal stages glycogenolysis gluconeogenesis. Here show...
Most women with a clinical presentation consistent ovarian cancer have benign conditions. Therefore methods to distinguish from those conditions would be beneficial. We describe the development and preliminary evaluation of serum-based multivariate assay for cancer. This hypothesis-driven study examined whether an informative pattern could detected in stage I disease that persists through later stages.Sera, collected under uniform protocols multiple institutions, representing 176 cases 187...
FDA-cleared ovarian cancer biomarkers are limited to CA-125 and HE4 for monitoring recurrence OVA1, a multivariate panel consisting of four additional biomarkers, referring patients specialist. Due relatively poor performance these tests, more accurate broadly applicable needed. We evaluated the dysregulation 259 candidate markers in serum samples from 499 patients. Sera were collected prospectively at 11 monitored sites under single well-defined protocol. All stages common benign...