A5080339195- Monoclonal and Polyclonal Antibodies Research
- Immunotherapy and Immune Responses
- T-cell and B-cell Immunology
- Immune Cell Function and Interaction
- Chronic Lymphocytic Leukemia Research
- HER2/EGFR in Cancer Research
- Glycosylation and Glycoproteins Research
- CAR-T cell therapy research
- Cell Adhesion Molecules Research
- Immune cells in cancer
- Chronic Myeloid Leukemia Treatments
- Peptidase Inhibition and Analysis
- Nitric Oxide and Endothelin Effects
- Autophagy in Disease and Therapy
- Cancer Cells and Metastasis
- Advanced Breast Cancer Therapies
- Cellular transport and secretion
- Hedgehog Signaling Pathway Studies
- Pancreatic and Hepatic Oncology Research
- Complement system in diseases
- Biochemical and Structural Characterization
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Phagocytosis and Immune Regulation
- Immune Response and Inflammation
- Phytoplasmas and Hemiptera pathogens
Genentech
2011-2015
Icahn School of Medicine at Mount Sinai
2012
Karolinska Institutet
2012
Howard Hughes Medical Institute
2011
University of Iowa
2011
Yale University
2004-2008
Ludwig Cancer Research
2004-2008
Ames National Laboratory
2007
Pfizer (United States)
2005
Cancer Research Institute
2004
Abstract Dendritic cells (DCs) have a unique ability to stimulate naive T cells. Recent evidence suggests that distinct DC subsets direct different classes of immune responses in vitro and vivo. In humans, the monocyte-derived CD11c+ DCs induce produce Th1 cytokines vitro, whereas CD11c− plasmacytoid cell-derived elicit production Th2 cytokines. this paper we report administration either Flt3-ligand (FL) or G-CSF healthy human volunteers dramatically increases subsets, precursors, blood. FL...
Sensory and signaling pathways are exquisitely organized in primary cilia. Bardet-Biedl syndrome (BBS) patients have compromised cilia signaling. BBS proteins form the BBSome, which binds Rabin8, a guanine nucleotide exchange factor (GEF) activating Rab8 GTPase, required for ciliary assembly. We now describe serum-regulated upstream vesicular transport events leading to centrosomal activation membrane formation. Using live microscopy imaging, we show that upon serum withdrawal is observed...
Chitin is a ubiquitous polysaccharide in fungi, insects, and parasites. We hypothesized that chitin size-dependent regulator of innate immunity. To test this hypothesis, we characterized the effects chitins different sizes on murine bronchoalveolar or peritoneal macrophages. In these studies, large fragments were inert, while both intermediate-sized (40-70 microm) small (SC; <40 microm, largely 2-10 stimulated TNF elaboration. contrast, only SC induced IL-10 The mediated by pathways involve...
In response to inflammatory stimuli, dendritic cells (DCs) trigger the process of maturation, a terminal differentiation program required initiate T-lymphocyte responses. A hallmark maturation is down-regulation endocytosis, which widely assumed restrict ability mature DCs capture and present antigens encountered after initial stimulus. We found that continue accumulate antigens, especially by receptor-mediated endocytosis phagocytosis. Internalized are transported normally late endosomes...
Abstract Recent single-cell studies of cancer in both mice and humans have identified the emergence a myofibroblast population specifically marked by highly restricted leucine-rich-repeat-containing protein 15 (LRRC15) 1–3 . However, molecular signals that underlie development LRRC15 + cancer-associated fibroblasts (CAFs) their direct impact on anti-tumour immunity are uncharacterized. Here mouse models pancreatic cancer, we provide vivo genetic evidence TGFβ receptor type 2 signalling...
Abstract Plasma membrane rupture (PMR) in dying cells undergoing pyroptosis or apoptosis requires the cell-surface protein NINJ1 1 . PMR releases pro-inflammatory cytoplasmic molecules, collectively called damage-associated molecular patterns (DAMPs), that activate immune cells. Therefore, inhibiting and may limit inflammation is associated with excessive cell death. Here we describe an anti-NINJ1 monoclonal antibody specifically targets mouse blocks oligomerization of NINJ1, preventing PMR....
Langerhans cells (LCs) represent a subset of immature dendritic (DCs) specifically localized in the epidermis and other mucosal epithelia. As surrounding keratinocytes can produce interleukin (IL)-15, cytokine that utilizes IL-2Rγ chain, we analyzed whether IL-15 could skew monocyte differentiation into LCs. Monocytes cultured for 6 d with granulocyte/macrophage colony-stimulating factor (GM-CSF) differentiate CD1a+HLA-DR+CD14−DCs (IL15-DCs). Agents such as lipopolysaccharide (LPS), tumor...
Nitric oxide (NO) is a highly diffusible and short-lived physiological messenger. Despite its nature, NO modifies thiol groups of specific cysteine residues in target proteins alters protein function via S-nitrosylation. Although intracellular S-nitrosylation posttranslational modification, the defined localization an source (nitric synthase, NOS) with has never been directly demonstrated. Endothelial NOS (eNOS) localized mainly on Golgi apparatus plasma membrane caveolae. Here, we show by...
Human BDCA3(+) dendritic cells (DCs), the proposed equivalent to mouse CD8α(+) DCs, are widely thought cross present antigens on MHC class I (MHCI) molecules more efficiently than other DC populations. If true, it is unclear whether this reflects specialization for presentation or a generally enhanced ability MHCI. We compared by DCs with BDCA1(+) using quantitative approach whereby were targeted distinct intracellular compartments receptor-mediated internalization. As expected, superior at...
Lysosomal storage diseases (LSDs) are a group of heterogeneous disorders caused by defects in lysosomal enzymes or transporters, resulting accumulation undegraded macromolecules metabolites. Macrophage numbers expanded several LSDs, leading to histiocytosis unknown pathophysiology. Here, we found that mice lacking the equilibrative nucleoside transporter 3 (ENT3) developed spontaneous and progressive macrophage-dominated histiocytosis. In absence ENT3, defective apoptotic cell clearance led...
Duplication of the single Golgi apparatus in protozoan parasite Trypanosoma brucei has been followed by tagging a putative enzyme and matrix protein with variants GFP. Video microscopy shows that new appears de novo, near to old Golgi, about two hours into cell cycle grows over two-hour period until it is same size as Golgi. endoplasmic reticulum (ER) export site follows exactly time course. Photobleaching experiments show not exclusive product ER site. Rather, supplied, at least part,...
Myoferlin and dysferlin are members of the ferlin family membrane proteins. Recent studies have shown that mutation or genetic disruption myoferlin promotes muscular dystrophy-related phenotypes in mice, which result impaired plasma integrity. However, no biological functions been ascribed to non-muscle tissues. Herein, using a proteomic analysis endothelial cell (EC) caveolae/lipid raft microdomains we identified these domains show is highly expressed ECs vascular The loss results lack...
Influenza A virus (IAV) infection is normally controlled by adaptive immune responses initiated dendritic cells (DCs). We investigated the consequences of IAV human primary DCs on their ability to function as antigen-presenting cells. was internalized both myeloid (mDCs) and plasmacytoid but only mDCs supported viral replication. Although infected efficiently presented endogenous antigens MHC class II, this not case for presentation I. Indeed, cross-presentation uninfected minute amounts...
There is a critical need for new antibacterial strategies to counter the growing problem of antibiotic resistance. In Gram-negative bacteria, outer membrane (OM) provides protective barrier against antibiotics and other environmental insults. The leaflet primarily composed lipopolysaccharide (LPS). Outer biogenesis presents many potentially compelling drug targets as this pathway absent in higher eukaryotes. Most proteins involved LPS biosynthesis transport are essential; however, few...