A5089352283- Endoplasmic Reticulum Stress and Disease
- Virus-based gene therapy research
- Viral Infectious Diseases and Gene Expression in Insects
- Neurological diseases and metabolism
- Long-Term Effects of COVID-19
- SARS-CoV-2 and COVID-19 Research
- COVID-19 Clinical Research Studies
- Glycosylation and Glycoproteins Research
- CRISPR and Genetic Engineering
- T-cell and B-cell Immunology
- Lipid Membrane Structure and Behavior
- Metabolism and Genetic Disorders
- Immune Cell Function and Interaction
- Immunodeficiency and Autoimmune Disorders
- Neurological Disorders and Treatments
- Hereditary Neurological Disorders
- Lipid metabolism and biosynthesis
- Inflammatory mediators and NSAID effects
- Biochemical Acid Research Studies
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Viral gastroenteritis research and epidemiology
- Bioactive Compounds and Antitumor Agents
- Biotin and Related Studies
- Ubiquitin and proteasome pathways
- Monoclonal and Polyclonal Antibodies Research
University of Catania
2024
West Virginia University
2018-2021
MetrioPharm (Germany)
2018
St. Jude Children's Research Hospital
2004-2015
A link exists between endoplasmic reticulum (ER) biogenesis and the unfolded protein response (UPR), a complex set of signaling mechanisms triggered by increased demands on folding capacity ER. The UPR transcriptional activator X-box binding 1 (XBP1) regulates expression proteins that function throughout secretory pathway is necessary for development an expansive ER network. We previously demonstrated overexpression XBP1(S), active form XBP1 generated UPR-mediated splicing Xbp1 mRNA,...
To generate sufficient clinical-grade vector to support a phase I/II clinical trial of adeno-associated virus serotype 8 (AAV8)-mediated factor IX (FIX) gene transfer for hemophilia B, we have developed large-scale, good manufacturing practice (GMP)-compatible method production and purification. We used 293T-based two-plasmid transient transfection system coupled with three-column chromatography purification process produce high-quality self-complementary AAV2/8 FIX vector. Two consecutive...
Self-complementary AAV (scAAV) vector genomes contain a covalently closed hairpin derived from mutated inverted terminal repeat that connects the two monomer single-stranded into head-to-head or tail-to-tail dimer. We found during quantitative PCR (qPCR) this structure inhibits amplification of proximal amplicons and causes systemic underreporting copy number by as much 10-fold. show cleavage scAAV with restriction endonuclease to liberate restores amplification, we implement procedure in...
Stimulated B-lymphocytes differentiate into plasma cells committed to antibody production. Expansion of the endoplasmic reticulum and Golgi compartments is a prerequisite for high rate synthesis, assembly, secretion immunoglobulins. The bacterial cell wall component lipopolysaccharide (LPS) stimulates murine B-cells proliferate antibody-secreting that morphologically resemble cells. LPS activation CH12 augmented phospholipid production initiated genetic program, including elevated expression...
The SARS-CoV-2 pandemic is impacting the global population. This study was designed to assess interplay of antibodies with cytokine response in patients. We demonstrate that significant levels anti-SARS-CoV-2 antibody receptor binding domain (RBD), nucleocapsid, and spike S1 subunit develop over first 10 20 days infection. majority patients produced against all three antigens (219/255 SARS-CoV-2+ patient specimens, 86%), suggesting a broad viral proteins. Antibody were different based on...
Pantothenate kinase-associated neurodegeneration, PKAN, is an inherited disorder characterized by progressive impairment in motor coordination and caused mutations PANK2, a human gene that encodes one of four pantothenate kinase (PanK) isoforms. PanK initiates the synthesis coenzyme A (CoA), essential cofactor plays key role energy metabolism lipid synthesis. Most PANK2 reduce or abolish activity enzyme. This evidence has led to hypothesis lower CoA might be underlying cause...
Lipid metabolism requires CoA, an essential cofactor found in multiple subcellular compartments, including the peroxisomes. In liver, CoA levels are dynamically adjusted between fed and fasted states. Elevated state driven by increased synthesis; however, this also correlates with decreased expression of Nudix hydrolase (Nudt)7, major CoA-degrading enzyme liver. Nudt7 resides peroxisomes, we overexpressed mouse livers to determine its effect on size composition hepatic pool overexpression...
CTP:phosphocholine cytidylyltransferase (CCT) is a key rate-controlling enzyme in the biosynthetic pathway leading to principle membrane phospholipid, phosphatidylcholine. CCTalpha predominant isoform expressed mammalian cells. To investigate role of development and function B-lymphocytes, mice with B-lymphocytes that selectively lacked were derived using CD19-driven Cre/loxP system. When challenged T-cell-dependent antigen, animals harboring CCTalpha-deficient B-cells exhibited hyper-IgM...
Free-standing, high aspect ratio sulfur-doped carbon nanodot-based hybrid nanowires with a microtubular were synthesized using self-recognition and self-assembly processes of tubulin, biological molecule precursor the cytoskeletal microtubule. Physicochemical characterizations (e.g., morphology, diameter, spectral characteristics, etc.) such user-synthesized bionanowires performed classical atomic spectroscopic techniques, whereas bioactivity functionality testing was demonstrated by...
Self-complementary AAV (scAAV) vector genomes contain a covalently closed hairpin derived from mutated inverted terminal repeat that connects the two monomer single-stranded into head-to-head or tail-totail dimer.We found during quantitative PCR (qPCR) this structure inhibits amplification of proximal amplicons and causes systemic underreporting copy number by as much 10-fold.We show cleavage scAAV with restriction endonuclease to liberate restores amplification, we implement procedure in...
COVID-19, caused by the SARS-CoV-2 virus, has a global health crisis, necessitating deeper understanding of its pathophysiology. In this study, we explored immune and hematological dynamics in COVID-19 patients to gain insights into disease severity prognosis. Our findings revealed distinct cytokine profiles moderate severe cases.
Abstract The SARS-CoV-2 pandemic is continuing to impact the global population. This study was designed assess interplay of antibodies with systemic cytokine response in patients. We demonstrate that significant anti-SARS-CoV-2 antibody production Receptor Binding Domain (RBD), Nucleocapsid (N), and Spike S1 subunit (S1) develops over first 10 20 days infection. majority patients produced against all three antigens (219/255 positive patient specimens, 86%) suggesting a broad viral proteins....
Stimulated B‐lymphocytes differentiate into plasma cells committed to immunoglobulin production. The B‐cells proliferate and expand the endoplasmic reticulum enhance synthesis secretion. Cellular membrane lipid components increase in response stimulation using a genetic biochemical program of events. Selected genes fatty acid phospholipid are up‐regulated, most notably encoding Lipin1 choline phosphotransferase. cytidylyltransferase (CCT) controls rate phosphatidylcholine production but its...
Professional secretory cells possess an expansive endoplasmic reticulum (ER) to accommodate high‐rate protein production. ER biogenesis requires phospholipids and phospholipid synthesis fatty acids. Yet, the mechanisms that regulate acid supply when demand for increases are incompletely understood. A link exists between expansion unfolded response (UPR), a stress‐induced signaling pathway emanates from ER. The UPR transcriptional activator XBP‐1(S) is required proper development in...
B‐lymphocytes, or B‐cells, originate in the bone marrow and mature spleen lymph nodes. Upon activation with ligand, B‐cells proliferate differentiate either into memory immunoglobulin (Ig)‐secreting plasma cells. Plasma cells are distinct from possess a more extensive endoplasmic reticulum (ER) Golgi compartment to sustain high‐capacity Ig synthesis secretion. Phosphatidylcholine (PtdCho) is major lipid component of B‐cell membranes CDP‐choline pathway source PtdCho during differentiation...
B-lymphocytes expand the membrane network for synthesis and secretion of antibodies. We investigated mechanisms that drive biogenesis during differentiation CH12 B-cells. Phosphatidylcholine (PtdCho) phosphatidylethanolamine (PtdEtn) content per cell doubled after induced by LPS. PtdCho acquired shorter chain monounsaturated fatty acids, whereas PtdEtn remained a reservoir polyunsaturated species. Alteration composition was accounted increased transcription Fasn Acac in first phase gene...