A5083266436- Virus-based gene therapy research
- Immune Cell Function and Interaction
- HIV Research and Treatment
- Immunotherapy and Immune Responses
- Monoclonal and Polyclonal Antibodies Research
- Immune Response and Inflammation
- Receptor Mechanisms and Signaling
- Viral gastroenteritis research and epidemiology
- Inflammasome and immune disorders
- Galectins and Cancer Biology
- T-cell and B-cell Immunology
- interferon and immune responses
- Retinal Diseases and Treatments
- Lysosomal Storage Disorders Research
- CAR-T cell therapy research
- Advanced Glycation End Products research
- Spondyloarthritis Studies and Treatments
- Peptidase Inhibition and Analysis
- Polyomavirus and related diseases
- Herpesvirus Infections and Treatments
- Eosinophilic Esophagitis
- Autoimmune and Inflammatory Disorders Research
- Neuroinflammation and Neurodegeneration Mechanisms
- Plant Virus Research Studies
- Immune cells in cancer
Michigan State University
2015-2024
Touro University California
2021
Michigan United
2010-2018
Laboratory of Molecular Genetics
2015
Western University of Health Sciences
2013
Physical Sciences (United States)
2012
Duke Medical Center
2004-2010
Seoul National University Hospital
2010
Duke University Hospital
2010
Duke University
2005
ER aminopeptidase 1 (ERAP1) customizes antigenic peptide precursors for MHC class I presentation and edits the repertoire. Coding single nucleotide polymorphisms (SNPs) in ERAP1 were recently linked with predisposition to autoimmune disease, suggesting a link between pathogenesis of autoimmunity ERAP1-mediated Ag processing. To investigate this possibility, we analyzed effect that disease-linked SNPs have on processing by vitro. Michaelis-Menten analysis revealed presence affects Michaelis...
Significance The human immune system fights disease by eradicating sick cells after first recognizing that they are infected or cancerous. This is achieved specialized detect on the surface of other small molecules called antigenic peptides. Pathogens and cancer can evade stopping generation We designed, synthesized evaluated artificial effectively block a group enzymes key for production destruction show these compounds enhance peptides in reaction toward cancer. Inhibitors this kind may...
Abstract T cell exhaustion represents one of the most pervasive strategies tumors employ to circumvent immune system. Although repetitive, cognate TCR signaling is recognized as primary driving force behind this phenomenon, and it remains unknown what other forces drive in tumor microenvironment (TME). In study, we show that activation self-ligand SLAMF7 receptor on cells induced STAT1 STAT3 phosphorylation, expression multiple inhibitory receptors, transcription factors associated with...
ABSTRACT Nearly 50 years ago, the discovery of interferon prompted notion that host cells innately respond to viral invasion. Since time, technological advances have allowed this response be extensively characterized and dissected in vitro. However, these only recently been applied highly complex, vivo biological systems. To end, we exploited high-titer adenovirus (Ad) vectors globally investigate innate immune nonenveloped infection vivo. Our results indicated a potent cellular...
Abstract Endoplasmic reticulum aminopeptidases 1 and 2 (ERAP1 ERAP2) cooperate to trim antigenic peptide precursors for loading onto MHC class I molecules help regulate the adaptive immune response. Common coding single nucleotide polymorphisms in ERAP1 ERAP2 have been linked with predisposition human diseases ranging from viral bacterial infections autoimmunity cancer. It has hypothesized that altered Ag processing by these enzymes is a causal link disease etiology, but molecular mechanisms...
More than 300 human clinical trials utilize recombinant adenoviruses (rAds) as a gene transfer vector, confirming that rAds continue to be of high interest. A primary weakness is their known propensity trigger an innate, proinflammatory immune response rapidly after high-dose, systemic administration. In this study, we investigated what affects pre-emptive treatment with anti-inflammatory glucocorticoids might have upon Ad vector-triggered inflammatory responses. We found simple pretreatment...
Objective: Chronic immune activation and elevated numbers of circulating activated monocytes (CD16+) are implicated in HIV-associated neuroinflammation. The objective was to compare the level CD16+ IFN-γ-inducible protein 10 (IP-10) between HIV-infected cannabis users (HIV+MJ+) noncannabis (HIV+MJ−) determine whether in-vitro Δ9-Tetrahydrocannabinol (THC), a constituent cannabis, affected CD16 expression as well IP-10 production by monocytes. Design: levels from HIV+MJ− HIV+MJ+ donors were...
Ankylosing spondylitis (AS) is a chronic systemic arthritic disease that leads to significant disability and loss of quality life in the ∼0.5% worldwide human population it affects. There currently no cure for AS mechanisms underlying its pathogenesis remain unclear. highly genetic, with over 70% genetic risk being associated presence HLA-B27 endoplasmic reticulum aminopeptidase-1 (ERAP1) alleles. Furthermore, gene-gene interactions between ERAP1 alleles have recently been confirmed. Here,...
Cannabis is widely used in the United States, with an estimated prevalence of 9.5%. Certain cannabinoids <i>Cannabis sativa</i>, Δ<sup>9</sup>-tetrahydrocannabinol (THC) particular, possess immune-modulating and anti-inflammatory activity. Depending on context, activity may be beneficial (e.g., treating inflammatory diseases) or detrimental to normal immune defense against pathogens. The potential effect chronic neuroinflammation has gained recent attention. Monocyte migration brain been...
Abstract G‐protein coupled receptor kinase‐5 (GRK5) is a serine/threonine kinase discovered for its role in the regulation of signaling. Recent studies have shown that GRK5 also an important regulator signaling pathways stimulated by non‐GPCRs. This study was undertaken to determine physiological Toll‐like receptor‐4‐induced inflammatory vivo and vitro. Using mice genetically deficient (GRK5 −/− ) we demonstrate here positive lipopolysaccharide (LPS, TLR4 agonist)‐induced cytokine chemokine...
Abstract β‐Arrestins are scaffolding proteins implicated as negative regulators of TLR4 signaling in macrophages and fibroblasts. Unexpectedly, we found that β‐arrestin‐1 (β‐arr‐1) ‐2 knockout (KO) mice protected from TLR4‐mediated endotoxic shock lethality. To identify the potential mechanisms involved, examined plasma levels inflammatory cytokines/chemokines wild‐type (WT) β‐arr‐1 KO after lipopolysaccharide (LPS, a ligand) injection. Consistent with lethality, LPS‐induced cytokine were...
Endoplasmic reticulum aminopeptidase 1 (ERAP1) gene polymorphisms have been linked to several autoimmune diseases; however, the molecular mechanisms underlying these associations are not well understood. Recently, we demonstrated that ERAP1 regulates key aspects of innate immune response. Previous studies show be endoplasmic reticulum-localized and secreted during inflammation. Herein, investigate possible roles polymorphic variants may in modulating responses human peripheral blood...
Tight junctions (TJs) involve close apposition of transmembrane proteins between cells. Although TJ have been studied in detail, the role lipids is largely unknown. We addressed very long-chain (VLC ≥26) ceramides TJs using diabetes-induced loss blood-retinal barrier as a model. VLC fatty acids that incorporate into are produced by elongase elongation protein 4 (ELOVL4). ELOVL4 significantly reduced diabetic retina. Overexpression decreased basal permeability, inhibited vascular endothelial...
Aminoacyl-tRNA synthetases (ARSs) are ubiquitously expressed enzymes that ligate amino acids onto tRNA molecules. Genes encoding ARSs have been implicated in phenotypically diverse dominant and recessive human diseases. The charging of tRNAPHE with phenylalanine is performed by a tetrameric enzyme contains two alpha (FARSA) beta (FARSB) subunits. To date, mutations the genes these subunits (FARSA FARSB) not any disease. Here, we describe patient severe, lethal, multisystem, developmental...
Abstract G‐protein‐coupled receptor kinase 2 (GRK2) is a member of family originally discovered for its role in the phosphorylation and desensitization receptors. It expressed high levels myeloid cells are altered many inflammatory disorders including sepsis. To address physiological cell‐specific GRK2 inflammation, we generated mice bearing deletion (GRK2 ▵mye ). exhibited exaggerated cytokine/chemokine production, organ injury response to lipopolysaccharide (LPS, TLR4 ligand) when compared...
HIV/AIDS continue to devastate populations worldwide. Recent studies suggest that vaccines induce beneficial immune responses in the mucosal compartment may improve efficacy of HIV vaccines. Adenovirus serotype 5 (Ad5)-based vectors remain a promising platform for development effective In an effort Ad5-based vaccines, even presence preexisting Ad5 immunity, we evaluated potential vaccine antigen-specific following sublingual (s.l.) administration, route not previously tested regard Ad-based...
Abstract Current advances in combined antiretroviral therapy have rendered HIV infection a chronic, manageable disease; however, the problem of persistent immune activation still remains despite treatment. The cell receptor SLAMF7 has been shown to be upregulated diseases characterized by chronic activation. In this study, we studied function cells patients and impacts signaling on peripheral We observed increased frequencies SLAMF7+ PBMCs HIV+ individuals clinical phenotype-dependent...
Multiple sclerosis (MS) is a chronic, debilitating condition characterized by CNS autoimmunity stemming from complex etiology involving both environmental and genetic factors. Our current understanding of MS points to dysregulation the immune system as pathogenic culprit, however, it remains unknown how many genes associated with increased susceptibility are involved. One such gene linked known regulate function self-ligand cell receptor SLAMF7.We subjected WT SLAMF7-/- mice multiple EAE...
Endoplasmic reticulum aminopeptidase-1 (ERAP1) is a multifunctional, ubiquitously expressed enzyme whose peptide-trimming role during antigen processing for presentation by MHC I molecules well established, however, ERAP1 in modulating global innate immune responses has not been described to date. Here we demonstrate that, relative wild type mice, mice lacking exhibit exaggerated early pathogen recognition, as characterized increased activation of splenic and hepatic NK NKT cells enhanced...