A5072503971- Immunotherapy and Immune Responses
- Extracellular vesicles in disease
- Endoplasmic Reticulum Stress and Disease
- RNA modifications and cancer
- RNA Interference and Gene Delivery
- Antibiotic Resistance in Bacteria
- Mitochondrial Function and Pathology
- Autophagy in Disease and Therapy
- Vitamin C and Antioxidants Research
- Long-Term Effects of COVID-19
- Coenzyme Q10 studies and effects
- ATP Synthase and ATPases Research
- Lipid Membrane Structure and Behavior
- Heme Oxygenase-1 and Carbon Monoxide
- RNA Research and Splicing
- Cystic Fibrosis Research Advances
- Vibrio bacteria research studies
- Cellular transport and secretion
- COVID-19 Clinical Research Studies
- Neurogenesis and neuroplasticity mechanisms
- Neuroinflammation and Neurodegeneration Mechanisms
- Respiratory Support and Mechanisms
- Biotin and Related Studies
- Immune cells in cancer
- Burkholderia infections and melioidosis
University of Pittsburgh
2013-2024
University of Pittsburgh Medical Center
2004-2021
Institute of Cell Biology
2016
Children's Hospital of Pittsburgh
2010
UPMC Hillman Cancer Center
2004
Johns Hopkins Medicine
2001
Johns Hopkins University
2001
G protein-coupled receptors (GPCRs) are classically characterized as cell-surface transmitting extracellular signals into cells. Here we show that central components of a GPCR signaling system comprised the melatonin type 1 receptor (MT
The immune response against transplanted allografts is one of the most potent reactions mounted by system. acute rejection has been attributed to donor dendritic cells (DCs), which migrate recipient lymphoid tissues and directly activate alloreactive T MHC molecules. Here, using a murine heart transplant model, we determined that only small number DCs reach investigated how this limited population efficiently initiates cell causes rejection. In our mouse efficient passage molecules...
Membrane and secretory proteins fold in the endoplasmic reticulum (ER), misfolded may be retained targeted for ER-associated protein degradation (ERAD). To elucidate mechanism by which an integral membrane ER is degraded, we studied fate of cystic fibrosis transmembrane conductance regulator (CFTR) yeast Saccharomyces cerevisiae. Our data indicate that CFTR resides stabilized strains defective proteasome activity or deleted ubiquitin-conjugating enzymes Ubc6p Ubc7p, thus demonstrating a bona...
Autophagy is a homeostatic process for recycling of proteins and organelles, induced by nutrient deprivation regulated oxygen radicals. Whether autophagy after traumatic brain injury (TBI) not established. We show that TBI in mice results increased ultrastructural biochemical evidence autophagy. Specifically, autophagosomal vacuoles secondary lysosomes were frequently observed cell processes axons ipsilateral regions electron microscopy, lipidated microtubule-associated protein light chain...
Significance The nuclear lamina is an integral component of all metazoan cells. While the individual constituents lamina, A- and B-type lamins, have been well studied, whether they exhibit a distinct spatial organization unclear. Using stochastic optical reconstruction microscopy, we identified two organizing principles lamina: lamin B1 forms outer concentric ring, its localization curvature-dependent. This suggests that role to stabilize shape by restraining outward protrusions A/C network....
New research shows that disease-associated microglia in neurodegenerative brains present features of elevated phagocytosis, lysosomal functions, and lipid metabolism, which benefit brain repair. The underlying mechanisms remain poorly understood. Intracellular pH (pHi) is important for regulating aerobic glycolysis microglia, where Na/H exchanger (NHE1) a key regulator by extruding H+ exchange Na+ influx. We report here post-stroke Cx3cr1-CreER+/-;Nhe1flox/flox (Nhe1 cKO) displayed...
Retinal ganglion cell axons are heavily myelinated (98%) and myelin damage in the optic nerve (ON) severely affects vision. Understanding molecular mechanism of oligodendrocyte progenitor (OPC) differentiation into mature oligodendrocytes will be essential for developing new therapeutic approaches ON demyelinating diseases. To this end, we developed a method isolation culture ON-derived lineage cells used it to study OPC differentiation. A critical aspect cellular is...
Abstract A stable mitochondrial pool is crucial for healthy cell function and survival. Altered redox biology can adversely affect mitochondria through induction of a variety death survival pathways, yet the understanding their dysfunction in primary human cells specific disease states, including asthma, modest. Ferroptosis traditionally considered an iron dependent, hydroperoxy-phospholipid executed process, which induces cytosolic damage to drive programmed death. However, this report we...
The major protein component in secreted very low density lipoproteins (VLDL) is apoB, and it established that these particles can reach sizes approaching 100 nm. We previously employed a cell-free system to investigate the nature of vesicles which this large cargo exits endoplasmic reticulum (ER) (Gusarova, V., Brodsky, J. L., Fisher, E. A. (2003) Biol. Chem. 278, 48051-48058). found apoB-containing exit ER as dense lipid-protein complexes regardless final further expansion occurs via...
Despite the role of donor-specific antibodies (DSAs) in recognizing major histocompatibility complex (MHC) antigens and mediating transplant rejection, how where recipient B cells lymphoid tissues encounter donor MHC remains unclear. Contrary to dogma, we demonstrated here that migration leukocytes out skin or heart allografts is not necessary for T cell allosensitization mice. We found mouse cardiac human grafts release cell-free via extracellular vesicles (EVs) are captured by subcapsular...
Klebsiella pneumoniae carbapenemase-producing K. (KPC-Kp) bloodstream infections are associated with high mortality. We studied clinical KPC-Kp isolates to investigate mechanisms of resistance complement, a key host defense against infection.
Abstract Dendritic cells (DC) are professional APC that control the balance between T cell immunity and tolerance. Genetic engineering of DC to regulate outcome immune response is an area intense research. Galectin (gal)-1 endogenous lectin binds glycoproteins exerts potent regulatory effects on cells. Consequently, gal-1 participates in central deletion thymocytes therapeutic experimental models cell-mediated autoimmune disorders graft-vs-host disease. Together, these observations strongly...
In the aging population, lower urinary tract (LUT) dysfunction is common and often leads to storage voiding difficulties classified into overlapping symptom syndromes. Despite prevalence consequences of these syndromes, LUT disorders continue be undertreated simply because there are few therapeutic options. function structure were assessed in aged (>25 months) male female Fischer 344 rats randomized oral treatment with a purine nucleoside phosphorylase (PNPase inhibitor) 8-aminoguanine...
Pregnancy is an immunological paradox where despite a competent maternal immune system, regulatory mechanisms at the fetoplacental interface and secondary lymphoid tissues (SLTs) circumvent rejection of semi-allogeneic concepti. Small extracellular vesicles (sEVs) are vehicle for intercellular communication; nevertheless, role sEVs in transport antigens to SLTs has not been conclusively demonstrated. Using mice which conceptus generates fluoroprobe-tagged shed by plasma membrane or released...
NADPH oxidase 4 (NOX4) regulates endothelial inflammation by producing hydrogen peroxide (H2O2) and to a lesser extent O2•-. The ratio of NOX4-derived H2O2 O2•- can be altered coenzyme Q (CoQ) mimics. Therefore, we hypothesize that cytochrome b5 reductase 3 (CYB5R3), CoQ abundant in vascular cells, inflammatory activation. To examine CYB5R3 vivo, created tamoxifen-inducible endothelium-specific Cyb5r3 knockout mice (R3 KO). Radiotelemetry measurements systolic blood pressure showed systemic...
Introduction Klebsiella pneumoniae ( Kp ) is a common cause of hospital-acquired pneumonia. Although previous studies have suggested that evasion phagocytic uptake virulence determinant , few examined phagocytosis sensitivity in clinical isolates. Methods We screened 19 respiratory isolates were previously assessed for mucoviscosity their to macrophage uptake, and evaluated as functional correlate vivo pathogenicity. Results The displayed heterogeneity the susceptibility with 14 out...
Francisella tularensis is a gram-negative, intracellular pathogen which can cause serious, potentially fatal, illness in humans. Species of F. are found across the Northern Hemisphere and infect broad range host species, including Factors affecting persistence environment its epidemiology not well understood, however, ability to enter viable but non-culturable state (VBNC) may be important. A bacteria, many pathogens, have been observed VBNC response stressful environmental conditions, such...
Abstract Fused in sarcoma (FUS) is a predominantly nuclear multifunctional RNA/DNA‐binding protein that regulates multiple aspects of gene expression. FUS mutations are associated with familial amyotrophic lateral sclerosis (fALS) and frontotemporal lobe degeneration (FTLD) humans. At the molecular level, mutated reduced nucleus but accumulates cytoplasmic granules. Oligodendrocytes (OL) carrying clinically relevant contribute to non‐cell autonomous motor neuron disease progression,...
The cell-surface glycocalyx serves as a physiological barrier regulating cellular accessibility to macromolecules and other cells. Conventional characterization has largely been morphological rather than functional. Here, we demonstrated direct anchoring of DNA origami nanotiles performed comprehensive comparison with traditional targeting the phospholipid bilayer (PLB) using cholesterol. While effectively accessed single-stranded initiators anchored on glycocalyx, their underlying PLB was...