A5049640251- Immunotherapy and Immune Responses
- Monoclonal and Polyclonal Antibodies Research
- NF-κB Signaling Pathways
- Galectins and Cancer Biology
- Metabolism, Diabetes, and Cancer
- Peptidase Inhibition and Analysis
- Cancer Immunotherapy and Biomarkers
- Protein Kinase Regulation and GTPase Signaling
- Cytokine Signaling Pathways and Interactions
- Fire dynamics and safety research
- Flame retardant materials and properties
- CAR-T cell therapy research
- Phagocytosis and Immune Regulation
- Immune Cell Function and Interaction
- PI3K/AKT/mTOR signaling in cancer
- T-cell and B-cell Immunology
- Angiogenesis and VEGF in Cancer
- Ubiquitin and proteasome pathways
- Cancer, Hypoxia, and Metabolism
- Immune Response and Inflammation
- Cardiac Structural Anomalies and Repair
- Bioinformatics and Genomic Networks
- Glycosylation and Glycoproteins Research
- Radio Frequency Integrated Circuit Design
- interferon and immune responses
Celldex Therapeutics (United States)
2006-2025
Leibniz University Hannover
2025
Helmholtz Zentrum München
2019-2024
Target (Germany)
2023
United States Fish and Wildlife Service
2015-2022
Ludwig-Maximilians-Universität München
2020
Atrium Health Wake Forest Baptist
2020
University of Cambridge
2017-2018
Cavendish Hospital
2017
University of North Carolina at Chapel Hill
2012-2015
The SHC proteins have been implicated in insulin receptor (IR) signaling. In this study, we used the sensitive two-hybrid assay of protein-protein interaction to demonstrate that interacts directly with IR. is mediated by amino acids 1 238 and therefore independent Src homology 2 domain. dependent upon IR autophosphorylation, since eliminated mutation ATP-binding site. addition, mutational analysis Asn-Pro-Glu-Tyr (NPEY) motif within juxtamembrane domain showed importance Asn, Pro, Tyr...
Insulin receptor substrate 1 (IRS-1) is a major of the insulin and has been implicated in signaling. Although IRS-1 thought to interact with receptor, nature interaction not defined. In this study, we used two-hybrid assay protein-protein yeast Saccharomyces cerevisiae study between human receptor. We demonstrate that forms specific complex cytoplasmic domain when both are expressed as hybrid proteins cells. show strictly dependent upon tyrosine kinase activity, since shows no...
Insulin receptor substrate-1 (IRS-1) and SHC become rapidly phosphorylated upon tyrosines after insulin-like growth factor I (IGFIR) activation. In this study we demonstrate that IRS-1, SHC, the p85 subunit of phosphatidylinositol 3-kinase interact directly specifically with IGFIR. The interaction all three proteins is dependent IGFIR kinase activity and, furthermore, substitution Tyr-950 Phe within NPEY motif eliminated both IRS-1 but had no effect interaction. We show residues 160-516...
Bone marrow-derived cells (BMCs) have been implicated as a modifiers of vascular growth either directly by transdifferentiation into endothelial (ECs) or indirectly through factor release. To examine these possibilities under physiological conditions, we developed model hypoxia-mediated angiogenesis in the mouse spinotrapezius muscle. This allows whole-mount analysis; therefore, morphology and location BMCs within network may be observed along with differentiation markers. We exposed bone...
We have utilized the yeast two-hybrid system to identify proteins that interact with cytoplasmic domain of insulin receptor. identified a human cDNA is splice variant GRB10 homolog GRB-IR, which we term GRB10/IR-SV1 (for GRB10/GRB-IR 1). The protein encoded by contains an SH2 and pleckstrin homology domain. Cloning full-length revealed predicted coding sequence was similar mouse protein, although contained 80-amino acid deletion. GRB-IR such intact distinct amino terminus. interaction...
Abstract Pattern recognition receptors are preferentially expressed on APCs allowing selective uptake of pathogens for the initiation antimicrobial immunity. In particular, C-type lectin receptors, including mannose receptor (MR), facilitate APC-mediated adsorptive endocytosis microbial glyconjugates. We have investigated potential antigenic targeting to MR as a means induce Ag-specific humoral and cellular hMR transgenic (hMR Tg) mice were generated allow specific with anti-hMR Ab, B11....
Insulin receptor substrate 2 (IRS-2) has recently been shown to be a of the insulin (IR). In this study we utilize yeast two-hybrid system and assays <i>in vitro</i> interaction demonstrate that IRS-2 interacts directly with IR insulin-like growth factor I receptor. We show that, like IRS-1, region contains putative phosphotyrosine binding SAIN elements(188-591) is sufficient for dependent upon NP<i>X</i>(p)Y (where (p)Y phosphotyrosine) motifs within juxtamembrane domains receptors....
Targeting recycling endocytic receptors with specific Abs provides a means for introducing variety of tumor-associated Ags into human dendritic cells (DCs), culminating in their efficient presentation to T cells. We have generated mAb (B11) against the mannose receptor that is rapidly internalized by DCs through receptor-mediated endocytosis. By genetically linking melanoma Ag, pmel17, Ab B11, we obtained fully fusion protein, B11-pmel17. Treatment B11-pmel17 resulted pmel17 context HLA...
We have identified two exons of the type III rat brain sodium channel alpha subunit gene that undergo mutually exclusive alternative RNA splicing to produce mRNAs coding either for an isoform predominant in neonatal (IIIN) or a different (IIIA) adult. These are 92 base pairs length and encode amino acids 203-232, which correspond part S3 most S4 transmembrane segments within domain I extracellular loop between them. Despite 21 nucleotide differences exons, only single acid at position 209 is...
The neutralizing antibody response to the protective antigen (PA) component of anthrax toxin elicited by approved vaccines is an accepted correlate for vaccine-mediated protection against anthrax. We reasoned that a human anti-PA monoclonal (MAb) selected on basis superior neutralization activity might provide potent fully MAb (also referred as MDX-1303 or Valortim) was chosen from large panel MAbs generated using transgenic mice immunized with recombinant PA solely in vitro neutralization....
Insulin receptor substrate 1 (IRS-1) and <i>src</i> homology collagen protein (SHC) are signaling proteins which rapidly phosphorylated on tyrosines after insulin (IR) activation. We have recently shown that both SHC IRS-1 interact with the tyrosine-phosphorylated NPEY motif of IR insulin-like growth factor I via non-SH2 domains (Gustafson, T. A., He, W., Craparo, Schaub, C. D., O'Neill, J.(1995) <i>Mol. Cell. Biol.</i> 15, 2500-2508; J., Gustafson, A.(1994) 14, 6433-6442; A.(1995) <i>J....
Abstract T-cell immunoglobulin and mucin domain 1 (TIM-1) is a type I transmembrane protein that was originally described as kidney injury molecule (KIM-1) due to its elevated expression in urine after renal injury. TIM-1 also upregulated several human cancers, most notably ovarian carcinomas, but has very restricted healthy tissues, thus representing promising target for antibody-mediated therapy. To this end, we have developed fully monoclonal IgG1 antibody specific the extracellular of...
ABSTRACT Background Mast cells (MCs) respond to an array of allergens that drive allergic and inflammatory diseases. Stem cell factor (SCF), the ligand for receptor KIT, is required MC survival function. Thymic stromal lymphopoietin (TSLP) alarmin promotes Type 2 inflammation in asthma other We describe CDX‐622, a bispecific antibody (bsAb), targets both SCF TSLP neutralize these distinct cytokines. Methods The bsAb CDX‐622 was developed from novel antagonist monoclonal antibodies (mAbs)...
Balanced control of T cell signaling is critical for adaptive immunity and protection from autoimmunity. By combining genetically engineered mouse models, biochemical analyses pharmacological interventions, we describe an unexpected dual role the tumor necrosis factor receptor–associated 6 (TRAF6) E3 ligase as both a positive negative regulator mucosa-associated lymphoid tissue 1 (MALT1) paracaspase. Although MALT1-TRAF6 recruitment indispensable nuclear κB in activated cells, TRAF6...
The CARMA1/CARD11-BCL10-MALT1 (CBM) complex bridges T and B cell antigen receptor (TCR/BCR) ligation to MALT1 protease activation canonical nuclear factor κB (NF-κB) signaling. Using unbiased mass spectrometry, we discover multiple serine phosphorylation sites in the C terminus after activation. Phospho-specific antibodies reveal that CBM-associated is transiently hyper-phosphorylated upon TCR/CD28 co-stimulation. We identify a dual role for CK1α as kinase essential CBM signalosome assembly...
CD27 is a costimulatory molecule that provides complementary target to the PD-1/PD-L1 checkpoint axis on T cells. Combining agonist antibody with blockade has shown synergistic antitumor activity in preclinical models, which led clinical studies of combination cancer patients. We theorized coupling costimulation bispecific (BsAb) may provide greater immune activating properties than combining individual mAbs due enhanced activation by cross-linking through PD-L1 and Fc receptors. To test...
Significance The worldwide prevalence of allergic and anaphylactic reactions has increased massively over recent decades. Mast cells basophils are essential drivers these diseases, releasing inflammatory mediators such as histamine. Here, we link the endolysosomal two-pore channel TPC1 to systemic anaphylaxis in vivo underlying mast cell function ex vivo. TPC1-deficient mice develop enhanced reflected by a drop body temperature slower recovery compared wild-type animals. Genetic deletion or...
ABSTRACT Objective: Skeletal muscle vasculature undergoes arteriogenesis to restore tissue perfusion and function following loss of blood flow. This process has been shown occur in large vessels ischemia, although recent studies suggest this may the microcirculation as well. We tested hypothesis that ischemia induces microvascular remodeling skeletal on scale capillary sub‐35 μm diameter arterioles. Methods: Ligations a feeding arteriole caudal‐half spinotrapezius were performed C57BL/6...
Dopamine (DA) is a physiological regulator of PRL secretion, exerting tonic inhibitory control. DA activates an inward rectifier K(+) (IRK) channel in rat lactotropes, causing membrane hyperpolarization and inhibition Ca(2+)-dependent action potentials. Both the activation this effector release are mediated by D(2)-type receptor pertussis toxin- sensitive G proteins. To study molecular basis physiologically relevant channel, homology-based PCR approach was employed to identify members IRK...