A5103234786- Cell Adhesion Molecules Research
- Mycobacterium research and diagnosis
- Ubiquitin and proteasome pathways
- Platelet Disorders and Treatments
- Tuberculosis Research and Epidemiology
- Antibiotic Resistance in Bacteria
- Protease and Inhibitor Mechanisms
- Autophagy in Disease and Therapy
- Growth Hormone and Insulin-like Growth Factors
- Immune Response and Inflammation
- Monoclonal and Polyclonal Antibodies Research
- Endoplasmic Reticulum Stress and Disease
- Bacteriophages and microbial interactions
- Escherichia coli research studies
- Advanced Breast Cancer Therapies
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Blood disorders and treatments
- Immune cells in cancer
- Chronic Lymphocytic Leukemia Research
- Signaling Pathways in Disease
- Antimicrobial Resistance in Staphylococcus
- Inflammasome and immune disorders
- Metabolism, Diabetes, and Cancer
- Coagulation, Bradykinin, Polyphosphates, and Angioedema
- T-cell and B-cell Immunology
Georgetown University
2025
MedStar Georgetown University Hospital
2025
Aarhus University
2022
Maine Medical Center
2022
Harvard University
1994-2019
University College Dublin
2014
Office of Infectious Diseases
2013
Genentech
2009
University of California, San Francisco
1992-2008
Cytoskeleton (United States)
2005
Single-cell mouse embryos were infected in vitro with recombinant lentiviral vectors to generate transgenic mice carrying the green fluorescent protein (GFP) gene driven by a ubiquitously expressing promoter . Eighty percent of founder carried at least one copy transgene, and 90% these expressed GFP high levels. Progeny inherited transgene(s) displayed fluorescence. Mice generated using muscle-specific T lymphocyte–specific promoters levels only appropriate cell types. We have also rats that...
Integrin Associated Protein (IAP) is a 50-kD membrane protein which copurifies with the integrin alpha v beta 3 from placenta and coimmunoprecipitates platelets. IAP also functionally associated signal transduction Leukocyte Response Integrin. Using tryptic peptide sequence, human murine cDNAs have been isolated. The has an extracellular amino-terminal immunoglobulin domain that binds all monoclonal anti-IAP antibodies. carboxy-terminal region highly hydrophobic three or five...
CITATION: Bitter, W., et al. 2009. Systematic genetic nomenclature for type VII secretion systems. PLoS Pathogens, 5(10): 1-6, doi: 10.1371/journal.ppat.1000507.
Mycobacteria are responsible for a number of human and animal diseases classical intracellular pathogens, living inside macrophages rather than as free-living organisms during infection. Numerous including Listeria monocytogenes, Shigella flexneri, Rickettsia rickettsii, exploit the host cytoskeleton by using actin-based motility cell to spread Here we show that Mycobacterium marinum, natural pathogen fish frogs an occasional humans, is capable actively inducing actin polymerization within...
ABSTRACT CD31 (PECAM-1) is a member of the immunoglobulin gene superfamily (IgSF) and has an important role in number endothelial cell functions including angiogenesis, inflammation, integrin activation cell-cell adhesion. both homotypic heterotypic adhesive properties common with other IgSF members contains multiple functional domains. Using chimaeric fusion proteins panel haematopoietic lines we show that can bind cells predominantly or manner depending on line used. Heterotypic binding...
Specialized secretion systems of pathogenic bacteria commonly transport multiple effectors that act in concert to control and exploit the host cell as a replication-permissive niche. Both Mycobacterium marinum tuberculosis genomes contain an extended region difference 1 (extRD1) locus encodes one such pathway, early secretory antigenic target 6 (ESAT-6) system (ESX-1) apparatus. ESX-1 is required for virulence proteins ESAT-6, culture filtrate protein 10 (CFP-10), EspA. Here, we show both...
Exocytosis of lysosomes from macrophages has been described as a response to microbial cytotoxins and haemolysins, well for releasing pro-inflammatory cytokines interleukin (IL)-1beta IL-18 during inflammasome activation. The mycobacterial ESX-1 secretion system, encoded in part by the Region Difference-1, is virulence factor necessary phagosome escape host cell lysis contact-dependent haemolysin Mycobacterium marinum. Here we show that M. marinum tuberculosis required Ca(2+)-dependent...
Pathogenic mycobacteria have the ability to persist in phagocytic cells and suppress immune system. The glycolipid lipoarabinomannan (LAM), particular its mannose cap, has been shown inhibit phagolysosome fusion induce immunosuppressive IL-10 production via interaction with receptor or DC-SIGN. Hence, current paradigm is that cap of LAM a crucial factor mycobacterial virulence. However, above studies were performed purified LAM, never live bacteria. Here we evaluate biological properties...
The adult respiratory distress syndrome is characterized by arterial hypoxemia as a result of increased alveolar capillary permeability to serum proteins in the setting normal hydrostatic pressures. Because bacterial sepsis prominent among various diverse conditions associated with altered permeability, we studied effect bacteremia attendant complement activation on sequestration microorganisms and leakage albumin lungs guinea pigs. Pneumococci were injected intravenously into pigs their...
We treated 69 patients who had hereditary angioedema with danazol to alleviate attacks of mucocutaneous involving the skin, oropharynx, and gastrointestinal tract, we documented continued efficacy for long-term treatment (1 6 years) angioedema. Significant dose-related, adverse reactions occurred, including weight gain, myalgias, headaches, microscopic hematuria, abnormal liver function tests, anxiety, altered libido, alopecia, dizziness, nausea. Alterations in menstrual were consistently...
A 50-kDa integrin-associated protein (IAP), identified by its role in activation of neutrophils extracellular matrix proteins, has recently been found to have a primary sequence that predicts five transmembrane domains, raising the possibility participates ion transport. In endothelial cells, proteins and anti-integrin antibodies shown trigger an influx [Ca2+]i via voltage-independent membrane channels. We now show monoclonal IAP block neutrophil completely inhibited fibronectin-stimulated...
Integrin-associated protein (IAP) is a 50-kDa membrane with an amino-terminal immunoglobulin domain and carboxyl-terminal multiply membrane-spanning region. It physically functionally associated the integrin alpha v beta 3 vitronectin receptor involved in increase intracellular calcium concentration, which occurs upon cell adhesion to extracellular matrix. Oxidative burst neutrophils can be induced or inhibited via IAP. Surprisingly, IAP also expressed on erythrocytes, have no known...
Regulation of leukocyte integrin avidity is a crucial aspect inflammation and immunity. The actin cytoskeleton has an important role in the regulation function, but cytoskeletal proteins involved are largely unknown. Because inflammatory stimuli that activate integrin-mediated adhesion human polymorphonuclear neutrophils (PMN) monocytes cause phosphorylation actin-bundling protein l -plastin, we tested whether -plastin was activation. -plastin-derived peptides included site (Ser-5) rapidly...
Integrin-associated protein (IAP/CD47) is physically associated with the alpha v beta 3 vitronectin (Vn) receptor and a functionally immunologically related integrin on neutrophils (PMN) monocytes. Anti-IAP antibodies inhibit multiple phagocyte functions, including Arg-Gly-Asp (RGD)-initiated activation of phagocytosis, chemotaxis, respiratory burst; PMN adhesion to entactin; transendothelial transepithelial migration at step subsequent tight intercellular adhesion. also binding Vn-coated...
Brief exposure of culture-derived human macrophages to laminin, a glycoprotein component all mammalian basement membranes that has molecular weight 1,000,000, led enhancement subsequent macrophage phagocytosis EAC4b, EAC3bi, and EAIgG (sheep erythrocytes sensitized with IgG anti-Forssman antibody). This effect on occurred both substrate-adherent fluid phase laminin. Preincubation macrophages, but not laminin augmentation phagocytosis, suggesting interaction the phagocytic cell, opsonized...
Like several other intracellular pathogens, Mycobacterium marinum (Mm) escapes from phagosomes into the host cytosol where it can polymerize actin, leading to motility that promotes spread neighboring cells. However, only approximately 25% of internalized Mm form actin tails, and fate remaining bacteria has been unknown. Here we show cytosolic access results in a new intricate pathogen interaction: macrophages ubiquitinate Mm, while shed their ubiquitinated cell walls. Phagosomal escape...
The Esx-1 (type VII) secretion system is critical for virulence of both Mycobacterium tuberculosis and marinum, highly conserved between the two species. Despite its importance, there has been no direct visualization until now. In M. we show that Mh3864, a novel substrate remains partially cell wall-associated after translocation, occurred in polar regions, indicating takes place these regions. Analysis infected host cells suggested activity similarly localized vivo. A core component...