A5078519231- Glycosylation and Glycoproteins Research
- Monoclonal and Polyclonal Antibodies Research
- Galectins and Cancer Biology
- Cell Adhesion Molecules Research
- HIV Research and Treatment
- Cellular transport and secretion
- T-cell and B-cell Immunology
- Ubiquitin and proteasome pathways
- Neuroinflammation and Neurodegeneration Mechanisms
- Immune Cell Function and Interaction
- interferon and immune responses
- HER2/EGFR in Cancer Research
- Amyotrophic Lateral Sclerosis Research
- Phagocytosis and Immune Regulation
- Alzheimer's disease research and treatments
- RNA regulation and disease
- Herpesvirus Infections and Treatments
- Cytomegalovirus and herpesvirus research
- Immune cells in cancer
- Peptidase Inhibition and Analysis
- Toxin Mechanisms and Immunotoxins
- CRISPR and Genetic Engineering
Alector (United States)
2023
Rockefeller University
2013-2015
Northwestern University
2005-2010
Immunoglobulins recognize and clear microbial pathogens toxins through the coupling of variable region specificity to Fc-triggered cellular activation. These proinflammatory activities are regulated, thus avoiding pathogenic sequelae uncontrolled inflammation by modulating composition Fc-linked glycan. Upon sialylation, affinities for Fcγ receptors reduced, whereas those alternative receptors, such as dendritic cell-specific intercellular adhesion molecule-3-grabbing nonintegrin...
The capsids of neurotropic herpesviruses have the remarkable ability to move in specific directions within axons. By modulating bidirectional capsid transport favor either retrograde (minus-end) or anterograde (plus-end) motion, these viruses travel sensory ganglia peripheral tissue at stages infection. using correlative motion analysis simultaneously monitor trafficking distinct viral proteins living neurons, we demonstrate that “tegument” are complexed moving removal a subset tegument from...
ABSTRACT The release of retroviruses from cells requires ubiquitination Gag and recruitment cellular proteins involved in endosome sorting, including the ESCRT-III Vps4 ATPase. In response to infection, have evolved an interferon-induced mechanism block virus replication through expression interferon-stimulated gene 15 (ISG15), a dimer homologue ubiquitin, which interferes with ubiquitin pathways cells. Previously, it has been reported that ISG15 inhibited E3 ligase, Nedd4, prevented...
Significance IgG molecules are capable of inducing pro- and antiinflammatory responses dependent on their fragment crystallizable domain (Fc) glycan composition. Antiinflammatory specifically triggered upon Fc sialylation, which decreases the binding affinity for type I receptors but enhances to II such as SIGN-R1, CD23, or human DC-SIGN. Structural analyses revealed that sialylation induces conformational changes in portion, is a prerequisite selective receptors. Here we generated an...
Retroviruses have evolved a mechanism for the release of particles from cell membrane that appropriates cellular protein complexes, referred to as ESCRT-I, -II, -III, normally involved in biogenesis multivesicular bodies. Three different classes late assembly (L) domains encoded Gag, with core sequences PPXY, PTAP, and YPXL, recruit components ESCRT machinery form budding complex virus release. Here, we highlight recent progress identifying role complexes facilitating budding,...
Members of the Nedd4 family E3 ubiquitin ligases bind L domain in avian sarcoma virus (ASV) Gag and facilitate viral particle release. Translational fusion ASV with an deletion (Δp2b) to proteins that comprise ESCRT-I, -II, -III (the endocytic sorting complexes required for transport) rescued both ubiquitination release from cells. The ESCRT-I factors Vps37C or Tsg101 were more effective rescue Gag/Δp2b budding than ESCRT-II factor Eap20 ESCRT-III component CHMP6. Thus ESCRT components can...
Antagonizing the CD47-signal regulatory protein (SIRP)α pathway, a critical myeloid checkpoint, promotes antitumor immunity. In this study, we describe development of AL008, pan-allelic, SIRPα-specific Ab that triggers degradation SIRPα and, concurrently, stimulates FcγR activation cells through an engineered Fc domain. AL008 showed superior enhancement phagocytosis tumor opsonized with Ag Abs compared another tested. Unlike ligand-blocking Abs, demonstrated single-agent activity by...
Abstract Antibodies (Ab) mediate pro-inflammatory effector functions through the engagement of Fc receptors (FcγRs) expressed on leukocytes. A complex, N-linked glycan attached to domain IgG regulates interaction FcγRs by maintaining in a biologically active conformation. However, attaching sialic acid sugar residues this Fc-associated reduces affinity for and confers binding an alternate class receptors, C-type lectins (DC-SIGN). This switch receptor specificity coincides with function vivo...