A5080118625- Lysosomal Storage Disorders Research
- Cellular transport and secretion
- Glycosylation and Glycoproteins Research
- Sphingolipid Metabolism and Signaling
- Bacterial biofilms and quorum sensing
- Cystic Fibrosis Research Advances
- Calcium signaling and nucleotide metabolism
- Protist diversity and phylogeny
- Carbohydrate Chemistry and Synthesis
- Click Chemistry and Applications
- Paleontology and Stratigraphy of Fossils
- Parkinson's Disease Mechanisms and Treatments
- Polysaccharides and Plant Cell Walls
- Vibrio bacteria research studies
- Erythrocyte Function and Pathophysiology
- Retinal Development and Disorders
- Neonatal Respiratory Health Research
- Plant-Microbe Interactions and Immunity
- Geological and Geochemical Analysis
- Gut microbiota and health
- Geochemistry and Elemental Analysis
- Ultrasound and Cavitation Phenomena
- Studies on Chitinases and Chitosanases
- Anesthesia and Neurotoxicity Research
Dalian Medical University
2024
Chongqing Medical University
2024
Second Affiliated Hospital of Chongqing Medical University
2024
Cincinnati Children's Hospital Medical Center
2008-2019
University of Cincinnati
2009-2015
University of Cincinnati Medical Center
2003-2011
Children's Hospital & Medical Center
2011
Pediatrics and Genetics
2007-2010
Pulmonary and Critical Care Associates
2004-2006
Pseudomonas aeruginosa secretes copious amounts of the redox-active phenazine, pyocyanin (PCN), during cystic fibrosis lung infection. PCN has been shown to interfere with a variety cellular processes in cultured epithelial cells. Here, by using two respiratory tract models infection, we demonstrate that mediates tissue damage and necrosis
Gaucher disease is caused by defective acid β-glucosidase (GCase) function. Saposin C a lysosomal protein needed for optimal GCase activity. To test the in vivo effects of saposin on GCase, deficient mice (C−/−) were backcrossed to point mutated (V394L/V394L) mice. The resultant (4L;C*) began exhibit CNS abnormalities ∼30 days: first as hindlimb paresis, then progressive tremor and ataxia. Death occurred ∼48 days due neurological deficits. Axonal degeneration was evident brain stem, spinal...
Pseudomonas aeruginosa produces copious amounts of the redoxactive tricyclic compound pyocyanin that kills competing microbes and mammalian cells, especially during cystic fibrosis lung infection. Cross-phylum susceptibility to suggests existence evolutionarily conserved physiological targets. We screened a Saccharomyces cerevisiae deletion library identify presumptive targets with expectation similar would be in humans. Fifty S. were provisionally identified, which 60% have orthologous...
The pharmacological chaperone, isofagomine (IFG), enhances acid β-glucosidase (GCase) function by altering folding, trafficking, and activity in wild-type Gaucher disease fibroblasts. vivo effects of IFG on GCase activity, its substrate levels, phenotype were evaluated using a neuronopathic mouse model, 4L;C* (V394L/V394L + saposin C-/-) that has CNS accumulation glucosylceramide (GC) glucosylsphingosine (GS) as well progressive neurological deterioration. administration to mice at 20 or 600...
Gaucher disease (GD) is caused by insufficient activity of acid β-glucosidase (GCase) resulting from mutations in GBA1. To understand the pathogenesis neuronopathic GD, induced pluripotent stem cells (iPSCs) were generated fibroblasts isolated three GD type 2 (GD2) and unaffected (normal carrier) individuals. The iPSCs converted to neural precursor (NPCs) which further differentiated into neurons. Parental GD2 as well iPSCs, NPCs, neurons had similar degrees GCase deficiency. Lipid analyses...
Pseudomonas aeruginosa (PA) is a major pathogen causing morbidity and ultimately mortality in patients afflicted with cystic fibrosis (CF) lung disease. One important virulence factor, pyocyanin (PCN), blue, redox-active compound that secreted such copious amounts by PA the CF lungs it determines colour of expectorated sputum. In this study, we discovered physiological concentrations PCN inactivate airway epithelial vacuolar ATPase, resulting reduced expression trafficking transmembrane...
Saposin B derives from the multi-functional precursor, prosaposin, and functions as an activity enhancer for several glycosphingolipid (GSL) hydrolases. Mutations in saposin present humans with phenotypes resembling metachromatic leukodystrophy. To gain insight into B's physiological functions, a specific deficiency was created mice by knock-in mutation of essential cysteine exon 7 prosaposin locus. No protein detected homozygotes (B−/−) mice, whereas saposins A, C D were at normal levels....
Saposins (A, B, C and D) are ∼80 amino acid stimulators of glycosphingolipid (GSL) hydrolases that derive from a single precursor, prosaposin. In both humans mice, prosaposin/saposin deficiencies lead to severe neurological deficits. The CD−/− mice with saposin D combined were produced by introducing genomic point mutations into critical cysteine in each these saposins. These develop phenotype ataxia, kyphotic posturing hind limb paralysis. Relative prosaposin null (∼30 days), had an...
Saposins A, B, C and D are derived from a common precursor, prosaposin (psap). The few patients with saposin deficiency develop Gaucher disease-like central nervous system (CNS) phenotype attributed to diminished glucosylceramide (GC) cleavage activity by acid β-glucosidase (GCase). in vivo effects of were examined creating mice selective absence (C−/−) using knock-in point mutation (cysteine-to-proline) exon 11 the psap gene. In C−/− mice, saposins B proteins present at near wild-type...
Gaucher disease is caused by mutations in GBA1 encoding acid β-glucosidase (GCase). Saposin C enhances GCase activity and protects from intracellular proteolysis. Structure simulations indicated that the mutant GCases, N370S (0 S), V394L (4L) D409V(9V)/H(9H), had altered function. To investigate vivo function of Gba1 mutants, mouse models were generated backcrossing above homozygous mice into deficient (C*) mice. Without saposin C, activities resultant tissues reduced ~50% compared with...
Abstract Background Prosaposin encodes, in tandem, four small acidic activator proteins (saposins) with specificities for glycosphingolipid (GSL) hydrolases lysosomes. Extensive GSL storage occurs various central nervous system regions mammalian prosaposin deficiencies. Results Our hypomorphic deficient mouse, PS-NA, exhibited 45% WT levels of brain saposins and showed neuropathology that included neuronal Purkinje cell loss. Impairment function was observed as early 6 wks demonstrated by...
Gaucher disease is a lysosomal storage caused by mutations in acid beta-glucosidase (GCase) leading to defective hydrolysis and accumulation of its substrates. Two L-type calcium channel (LTCC) blockers-verapamil diltiazem-have been reported modulate endoplasmic reticulum (ER) folding, trafficking, activity GCase human fibroblasts. Similarly, these LTCC blockers were tested with cultured skin fibroblasts from homozygous point-mutated mice (V394L, D409H, D409V, N370S) the effect enhancing...
Individual saposin A (A−/−) and B (B−/−)-deficient mice show unique phenotypes caused by insufficient degradation of myelin-related glycosphingolipids (GSLs): galactosylceramide galactosylsphingosine sulfatide, respectively. To gain insight into the interrelated functions saposins B, combined AB-deficient (AB−/−) were created knock-in point mutations domains on prosaposin locus. Saposin proteins undetectable in AB−/− mice, whereas prosaposin, C D expressed near wild-type (WT) levels....
Sonogenetics is an advanced ultrasound-based neurostimulation approach for targeting neurons in specific brain regions. However, the role of sonogenetics treating status epilepticus (SE) remains unclear. Here, we aimed to investigate effects ultrasound and MscL-G22S (a mechanosensitive ion channel that mediates Ca