A5074222588- Lysosomal Storage Disorders Research
- Cellular transport and secretion
- Glycosylation and Glycoproteins Research
- Trypanosoma species research and implications
- Erythrocyte Function and Pathophysiology
- Carbohydrate Chemistry and Synthesis
- Virus-based gene therapy research
- Calcium signaling and nucleotide metabolism
- Research on Leishmaniasis Studies
- Autophagy in Disease and Therapy
- RNA Interference and Gene Delivery
- Muscle Physiology and Disorders
- Biochemical and Molecular Research
- Endoplasmic Reticulum Stress and Disease
- Biomedical Research and Pathophysiology
- Extracellular vesicles in disease
- Mitochondrial Function and Pathology
- Toxoplasma gondii Research Studies
- Skin and Cellular Biology Research
- ATP Synthase and ATPases Research
- Pancreatic function and diabetes
- Neonatal Health and Biochemistry
- Galectins and Cancer Biology
- Ubiquitin and proteasome pathways
- RNA regulation and disease
St. Jude Children's Research Hospital
2014-2024
University of Tennessee Health Science Center
2004-2024
Weatherford College
2015
The Royal Free Hospital
2015
University College London
2015
Boston College
2005
University of Tennessee at Knoxville
1999
Saint Louis University
1998
Hanson Institute
1998
University of California, Los Angeles
1990-1998
In normal human fibroblasts, an enzymically active 85,000-dalton precursor form of beta-galactosidase is processed, via a number intermediates, into mature 64,000-dalton form. addition there inactive 32,000-dalton component and its 54,000-dalton precursor. fibroblasts from patients with combined deficiency neuraminidase these last two components are absent hardly any can be demonstrated. Nevertheless, in the mutant synthesized processed normally. The excessive intralysosomal degradation that...
Neuraminidases (sialidases) have an essential role in the removal of terminal sialic acid residues from sialoglycoconjugates and are distributed widely nature. The human lysosomal enzyme occurs complex with beta-galactosidase protective protein/cathepsin A (PPCA), is deficient two genetic disorders: sialidosis, caused by a structural defect neuraminidase gene, galactosialidosis, which loss activity secondary to deficiency PPCA. We identified full-length cDNA clone dbEST data base, predicted...
Subunit association of @-hexosaminidase was studied in intact fibroblasts using antisera that discriminate between free and associated a-chains.These were anti-&hexosaminidase A (anti-a@), which precipitated all a-chains, or associated; anti-@-hexosaminidase B (anti-Bo), those a-chains with 8; anti-a-chains, recognized only monomeric a-chains.After biosynthetic labeling, /.?-hexosaminidase its a-subunit immunoprecipitated from extracts cells medium the aid protein A-bearing Staphylococcus...
Both pathogen- and tissue damage-associated molecular patterns induce inflammation through toll-like receptors (TLRs), while sialic acid-binding immunoglobulin superfamily lectin (Siglecs) provide negative regulation. Here we report extensive direct interactions between these pattern recognition receptors. The promiscuous TLR binders were human SIGLEC-5/9 mouse Siglec-3/E/F. Mouse Siglec-G did not show appreciable binding to any TLRs tested. Correspondingly, Siglece deletion enhanced...
LAMP1 oversialylation results in excessive lysosomal exocytosis, promoting tumor invasion and drug resistance.
Several cell types secrete small membranous vesicles that contain cell-specific collections of proteins, lipids, and genetic material. The function these is to allow cell-to-cell signaling the horizontal transfer their cargo molecules. Here, we demonstrate muscle cells nano-sized release increases during differentiation. Analysis nanovesicles allowed us characterize them as exosome-like particles define potential role multifunctional protein Alix in biogenesis.
Coordinated regulation of the lysosomal and autophagic systems ensures basal catabolism normal cell physiology, failure either system causes disease. Here we describe an epigenetic rheostat orchestrated by c-MYC histone deacetylases that inhibits biogenesis concomitantly repressing expression transcription factors MiT/TFE FOXH1, autophagy genes. Inhibition abates binding to promoters genes, granting promoter occupancy members, TFEB TFE3, and/or regulator FOXH1. In pluripotent stem cells...
Expansion of fibrous connective tissue and abnormal deposition extracellular matrix (ECM) are at the basis many fibrotic diseases. Fibrosis can occur in response to both physiological pathological cues, including wound healing, remodeling/repair inflammation. Chronic fibrosis lead severe damage, organ failure death. Assessing extent is crucial for accurate diagnosis this condition. The use Masson's trichrome staining sections from skeletal muscle a fast method detection morphological...
Human GM1-gangliosidosis is caused by a genetic deficiency of lysosomal acid β-galactosidase (β-gal). The disease manifests itself either as an infantile, juvenile or adult form and primarily neurological disorder with progressive brain dysfunction. A mouse model lacking functional β-gal gene has been generated homologous recombination embryonic stem cell technology. Tissues from affected mice are devoid mRNA totally deficient in GM1-ganglioside-hydrolyzing capacity. Storage material was...
The protective protein was first discovered because of its deficiency in the metabolic storage disorder galactosialidosis. It associates with lysosomal beta-galactosidase and neuraminidase, toward which it exerts a function necessary for their stability activity. Human mouse proteins are homologous to yeast plant serine carboxypeptidases. Here, we provide evidence that this has enzymatic activity similar cathepsin A: 1) overexpression human COS-1 cells induces 3-4-fold increase A-like...
We have isolated two cDNAs encoding human lysosomal beta-galactosidase, the enzyme deficient in GM1-gangliosidosis and Morquio B syndrome, a beta-galactosidase-related protein. In total RNA from normal fibroblasts major mRNA of about 2.5 kilobases (kb) is recognized by cDNA probes. A minor transcript 2.0 kb visible only immunoselected polysomal RNA. heterogeneous pattern expression 2.5-kb beta-galactosidase observed different patients. The nucleotide sequences are extensively colinear....
Removal of sialic acid from glycoconjugates on the surface monocytes enhances their response to bacterial LPS. We tested hypothesis that endogenous sialidase activity creates a permissive state for LPS-induced cytokine production in human monocyte-derived DCs. Of four genetically distinct sialidases (Neu1-4), Neu1, Neu3, and Neu4 are expressed monocytes, but only Neu1 Neu3 up-regulated as cells differentiate into present DCs also intracellularly. contain greater amount than acid/mg total...