A5017939697- Lysosomal Storage Disorders Research
- Cellular transport and secretion
- Virus-based gene therapy research
- Glycosylation and Glycoproteins Research
- Lipid Membrane Structure and Behavior
- Adenosine and Purinergic Signaling
- Mosquito-borne diseases and control
- Chronic Lymphocytic Leukemia Research
- Chronic Myeloid Leukemia Treatments
- Neuroscience and Neuropharmacology Research
- T-cell and Retrovirus Studies
- Magnesium in Health and Disease
- Porphyrin and Phthalocyanine Chemistry
- Herpesvirus Infections and Treatments
- Supramolecular Self-Assembly in Materials
- Cytomegalovirus and herpesvirus research
- Galectins and Cancer Biology
- Neuroinflammation and Neurodegeneration Mechanisms
- Toxoplasma gondii Research Studies
- Autophagy in Disease and Therapy
- Endoplasmic Reticulum Stress and Disease
- Ion channel regulation and function
St. Jude Children's Research Hospital
2020-2024
University of Tennessee Health Science Center
2019-2024
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...
Endoplasmic reticulum-plasma membrane (ER-PM) junctions mediate Ca
Sialidosis (mucolipidosis I) is a glycoprotein storage disease, clinically characterized by spectrum of systemic and neurological phenotypes. The primary cause the disease deficiency lysosomal sialidase NEU1, resulting in accumulation sialylated glycoproteins/oligosaccharides tissues body fluids. Neu1
Alzheimer disease (AD) is characterized by aberrant amyloid precursor protein (APP) processing and lysosomal dysfunction. This study identifies two members of the multi-enzyme complex (LMC), neuraminidase 1 (Neu1) protective protein/cathepsin A (PPCA), as a critical regulators APP metabolism. Neu1 deficiency in human AD brains 5xFAD/Neu1-/- mice leads to sialic acid retention on its secretases, enhancing amyloidogenic cleavage Aβ42 production. Additionally, increases exocytosis, contributing...
Congenital deficiency of the lysosomal sialidase neuraminidase 1 (NEU1) causes storage disease, sialidosis, characterized by impaired processing/degradation sialo-glycoproteins and sialo-oligosaccharides, accumulation sialylated metabolites in tissues body fluids. Sialidosis is considered an ultra-rare clinical condition falls into category so-called orphan diseases, for which no therapy currently available. In this study we aimed to identify potential therapeutic modalities, targeting...
AAV-mediated gene therapy holds promise for the treatment of lysosomal storage diseases (LSDs), some which are already in clinical trials. Yet, ultra-rare subtypes LSDs, such as glycoproteinoses, have lagged. Here, we report on a long-term safety and efficacy preclinical study conducted murine model galactosialidosis, glycoproteinosis caused by deficiency protective protein/cathepsin A (PPCA). One-month-old Ctsa−/− mice were injected intravenously with high dose self-complementary AAV2/8...
Summary Neuraminidase 1 (Neu1) cleaves terminal sialic acids from sialoglycoproteins in endolysosomes and at the plasma membrane. As such, Neu1 regulates immune cells, primarily those of monocytic lineage. Here we examined how influences microglia by modulating sialylation full-length Trem2 (Trem2-FL), a multifunctional receptor that microglial survival, phagocytosis, cytokine production. When was deficient/downregulated, Trem2-FL remained sialylated, accumulated intracellularly, excessively...
Summary Endoplasmic reticulum–plasma membrane (ER-PM) junctions mediate Ca2+ flux across neuronal membranes. The properties of these contact sites are defined by their lipid content, but little attention has been given to glycosphingolipids (GSLs). Here, we show that GM1-ganglioside, an abundant GSL in membranes, is integral ER-PM junctions; it interacts with synaptic proteins/receptors and regulates signaling. In a model the neurodegenerative lysosomal storage disease, GM1-gangliosidosis,...
Abstract Sialidosis is a glycoprotein storage disease caused by deficiency of the lysosomal sialidase NEU1, which leads to pathogenic accumulation sialylated glycoproteins and oligosaccharides in tissues body fluids. The belongs group orphan disorders with no therapy currently available. Here, we have tested therapeutic potential AAV-mediated gene for treatment sialidosis mouse model disease. One-month-old Neu1 −/− mice were co-injected two scAAV2/8 vectors, expressing NEU1 its chaperone...
Endoplasmic reticulum-plasma membrane (ER-PM) junctions mediate Ca