A5025152050- Lysosomal Storage Disorders Research
- Cellular transport and secretion
- Enzyme Structure and Function
- Carbohydrate Chemistry and Synthesis
- Polyamine Metabolism and Applications
- Trypanosoma species research and implications
- Glycosylation and Glycoproteins Research
- Biochemical and Molecular Research
- Autoimmune and Inflammatory Disorders Research
- Neurogenetic and Muscular Disorders Research
- Toxoplasma gondii Research Studies
- Bacterial Genetics and Biotechnology
- Parkinson's Disease Mechanisms and Treatments
- Plant Virus Research Studies
- RNA modifications and cancer
- Studies on Chitinases and Chitosanases
- Neuroinflammation and Neurodegeneration Mechanisms
- RNA and protein synthesis mechanisms
- Bacteriophages and microbial interactions
- Biochemical and Structural Characterization
- Ubiquitin and proteasome pathways
- DNA Repair Mechanisms
- Chromosomal and Genetic Variations
- Monoclonal and Polyclonal Antibodies Research
- Mitochondrial Function and Pathology
Yale University
2007-2024
Northwestern University
2014-2018
General Department of Preventive Medicine
2017
Faculty of Public Health
2007
Chinese Academy of Sciences
1998
Glucocerebrosidase 1 ( GBA ) mutations responsible for Gaucher disease (GD) are the most common genetic risk factor Parkinson's (PD). Although link between GD and PD is well established, underlying molecular mechanism(s) not understood. We propose that glucosylsphingosine, a sphingolipid accumulating in GD, mediates pathology -associated PD. show that, whereas GD-related sphingolipids (glucosylceramide, sphingosine, sphingosine-1-phosphate) promote α-synuclein aggregation vitro ,...
Background: Neuronopathic Gaucher disease (nGD) is a rare neurodegenerative disorder caused by biallelic mutations in GBA and buildup of glycosphingolipids lysosomes. Neuronal injury cell death are prominent pathological features; however, the role individual types involvement microglia, blood-derived macrophages, immune infiltrates nGD pathophysiology remains enigmatic. Methods: Here, using single-cell resolution mouse brains, lipidomics, newly generated biomarkers, we found induction...
Abstract Biallelic mutations in Gba cause Gaucher disease (GD), a lysosomal disorder characterized by deficient glucocerebrosidase activity and the accumulation of glucosylceramide (GlcCer) glucosylsphingosine (GlcSph), primarily macrophages. Beyond macrophages, GD pathology affects additional hematopoietic lineages, contributing to immune dysregulation. Existing Mx1-Cre knockout models require induction protocols that lead gene deletion outside cells, limiting study hematopoietic-specific...
Transcriptional mechanisms remain poorly understood in trypanosomatid protozoa. In particular, there is no knowledge about the function of basal transcription factors, and an apparent rarity promoters for protein-coding genes transcribed by RNA polymerase (Pol) II. Here we describe a Trypanosoma brucei factor related to TATA-binding protein (TBP). Although this TBP-related (TBP-related 4 [TRF4]) has 31% identity TBP core domain, several key residues involved TATA box binding are not...
A salutary effect of treatments for Gaucher disease (GD) has been a reduction in the incidence avascular osteonecrosis (AVN). However, there are reports AVN patients receiving enzyme replacement therapy (ERT) , and it is not known whether related to individual treatments,
In Gaucher disease (GD), genetic deficiency of acid β-glucosidase leads to accumulation its substrate glucosylceramide (GlcCer) and glucosylsphingosine (GlcSph). Lipid-laden cells, most prominently seen as macrophages engorged with GlcCer GlcSph-laden lysosomes, trigger chronic metabolic inflammation multisystemic phenotypes. Among the pleiotropic effects inflammatory cascades, induction synthase accentuates primary defect. First-line therapies for adults GD type 1 include Enzyme Replacement...
Summary The Trypanosoma brucei genome is colonized by the site‐specific non‐LTR retrotransposon SLACS, or spliced leader‐associated conserved sequence, which integrates exclusively into leader (SL) RNA genes. Although there evidence that interference (RNAi) machinery regulates SLACS transcript levels, we do not know whether RNAi deficiency affects genomic stability of nor understand mechanism transcription. Here, report prolonged culturing RNAi‐deficient T. cells, but wild‐type results in...
Despite the global medical needs associated with Staphylococcus aureus infections, no licensed vaccines are currently available. We identified and characterized a protein annotated as an epidermin leader peptide processing serine protease (EpiP), novel S. vaccine candidate. In addition, we determined structure of recombinant (rEpiP) by X-ray crystallography. The crystal revealed that rEpiP was cleaved somewhere between residues 95 100, found cleavage occurs through autocatalytic...
In addition to catalyzing a central step in glycolysis, enolase assumes remarkably diverse set of secondary functions different organisms, including transcription regulation as documented for the oncogene c-Myc promoter-binding protein 1. The apicomplexan parasite Toxoplasma gondii differentially expresses two nuclear-localized, plant-like enolases: 1 (TgENO1) latent bradyzoite cyst stage and 2 (TgENO2) rapidly replicative tachyzoite stage. A 2.75 Å resolution crystal structure 1, second be...
GBA is the major risk gene for Parkinson's disease (PD) and Dementia with Lewy Bodies (DLB), two common α-synucleinopathies cognitive deficits. We investigated role of mutant in decline by utilizing Gba (L444P) mutant, SNCA transgenic (tg), Gba-SNCA double mice. Notably, mice showed early deficits but lacked PD-like motor or α-synuclein pathology. Conversely, tg displayed age-related deficits, without abnormalities. exhibited both exacerbated accompanied greater cortical phospho-α-synuclein...
Toxoplasma gondii, an Apicomplexan parasite, causes significant morbidity and mortality, including severe disease in immunocompromised hosts devastating congenital disease, with no effective treatment for the bradyzoite stage. To address this, we used Tropical Disease Research database, crystallography, molecular modeling, antisense to identify characterize a range of potential therapeutic targets toxoplasmosis. Phosphoglycerate mutase II (PGMII), nucleoside diphosphate kinase (NDK),...
RcsB, the transcription-associated response regulator of Rcs phosphorelay two-component signal transduction system, activates cell stress responses associated with desiccation, wall biosynthesis, division, virulence, biofilm formation, and antibiotic resistance in enteric bacterial pathogens. RcsB belongs to FixJ/NarL family transcriptional regulators, which are characterized by a highly conserved C-terminal DNA-binding domain. The N-terminal domain receiver domains. This contains...
Gaucher disease is reckoned for extreme phenotypic diversity that does not show consistent genotype/phenotype correlations. In Argentina, a national collaborative group, Grupo Argentino de Diagnóstico y Tratamiento la Enfermedad Gaucher, GADTEG, have delineated uniformly severe type 1 manifestations presenting in childhood with large burden of irreversible skeletal disease. Here using Long-Read Single Molecule Real-Time (SMRT) Sequencing GBA1 locus, we RecNciI allele highly prevalent and...
Abstract GBA is the major risk gene for Parkinson’s disease (PD) and Dementia with Lewy Bodies (DLB), two common α-synucleinopathies cognitive deficits. We investigated role of mutant in decline by utilizing Gba (L444P) mutant, SNCA transgenic (tg), Gba-SNCA double mice. Notably, mice showed early deficits but lacked PD-like motor or α-synuclein pathology. Conversely, tg displayed age-related deficits, without abnormalities. exhibited both exacerbated accompanied greater cortical...
Background/Objectives: Gaucher disease (GD) is characterized by significant phenotypic heterogeneity, even among patients with identical GBA1 genotypes, suggesting the role of genetic and/or epigenetic modifiers. The enzymatic defect and pathological accumulation glucosylceramide (GlcCer) lead to chronic metabolic inflammation, potentially interacting other biological pathways influence expression. Methods: This study leveraged one world’s most deeply phenotyped cohorts GD patients, drawn...
Spermidine N-acetyltransferase (SpeG) acetylates and thus neutralizes toxic polyamines. Studies indicate that SpeG plays an important role in virulence pathogenicity of many bacteria, which have evolved SpeG-dependent strategies to control polyamine concentrations survive their hosts. In Escherichia coli, the two-component response regulator RcsB is reported be subject Nε-acetylation on several lysine residues, resulting reduced DNA binding affinity transcription small RNA rprA; however,...
Abstract BACKGROUND A salutary effect of treatments for Gaucher disease (GD) has been reduction in the incidence avascular osteonecrosis (AVN). However, there are reports AVN patients receiving enzyme replacement therapy (ERT), and it is not known whether related to individual treatments, GBA genotypes, phenotypes, biomarkers residual activity or anti-drug antibodies. OBJECTIVE Prompted by development several ERT, we aimed delineate determinants ERT eliglustat substrate (SRT) during 20 years...