- Rheumatoid Arthritis Research and Therapies
- Cell Adhesion Molecules Research
- Monoclonal and Polyclonal Antibodies Research
- Systemic Lupus Erythematosus Research
- Immune Cell Function and Interaction
- Peptidase Inhibition and Analysis
- Immune cells in cancer
- Banana Cultivation and Research
- T-cell and B-cell Immunology
- Protease and Inhibitor Mechanisms
- Advanced Proteomics Techniques and Applications
- Viral Infections and Immunology Research
- Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis
- Immune Response and Inflammation
- Advanced Biosensing Techniques and Applications
- Cytokine Signaling Pathways and Interactions
- Gene expression and cancer classification
- Polymer-Based Agricultural Enhancements
- Cancer-related molecular mechanisms research
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Plant Micronutrient Interactions and Effects
- S100 Proteins and Annexins
Johns Hopkins University
2020-2024
Johns Hopkins Medicine
2020-2024
Cornell University
2007
Abstract Cryptic peptides, hidden from the immune system under physiologic conditions, are revealed by changes to MHC class II processing and hypothesized drive loss of tolerance self-antigens in autoimmunity. Rheumatoid arthritis (RA) is an autoimmune disease characterized responses citrullinated self-antigens, which arginine residues converted citrullines. Here, we investigate hypothesis that citrullination exposes cryptic peptides modifying protein structure proteolytic cleavage. We show...
Systemic lupus erythematosus (SLE) is a systemic autoimmune disease with dramatic sex bias, affecting 9-times more women than men. Activation of toll-like receptor 7 (TLR7) by self-RNA central pathogenic process leading to aberrant production type-I interferon (IFN) in SLE, but the specific RNA molecules that serve as TLR7 ligands have not been defined. We therefore sought identify female-specific endogenous RNAs containing canonical stimulatory motifs. By leveraging gene expression data and...
Peptidylarginine deiminase IV (PAD4) post-translationally converts arginine residues in proteins to citrullines and is implicated playing a central role the pathogenesis of several diseases. Although PAD4 was historically thought be nuclear enzyme, recent evidence has revealed more complex localization with additional cytosolic cell surface activity. However, mechanisms by which PAD4, lacks conventional secretory signal sequences, traffics extranuclear localizations are unknown. In this...
ABSTRACT Synthetic chelators are commonly used in hydroponic media to solubilize iron (Fe); however, the fate of these is unknown. This study examined persistence three synthetic chelators, ethylenediaminetetraacetate (EDTA), diethylenetriaminepentaacetate (DTPA), and ethylenediaminedisuccinate (EDDS) a bench-scale lettuce production system. The EDDS concentration decreased rapidly within 7d, most likely due biodegradation. EDTA DTPA concentrations stayed steady throughout experiments...
Although anti-citrullinated protein autoantibodies (ACPAs) are a hallmark serological feature of rheumatoid arthritis (RA), the mechanisms and cellular sources behind generation RA citrullinome remain incompletely defined. Peptidylarginine deiminase IV (PAD4), one key enzymatic drivers citrullination in joint, is expressed by granulocytes monocytes; however, subcellular localization contribution monocyte-derived PAD4 to citrullinated autoantigens underexplored. In this study, we demonstrate...
Citrullinated proteins are hallmark targets of autoantibodies in rheumatoid arthritis (RA). Our study was undertaken to determine the effect autocitrullination on recognition peptidylarginine deiminases (PADs) 2 and 4 by RA.Autocitrullination sites PAD2 PAD4 were determined mass spectrometry literature review. Antibodies against native autocitrullinated PADs 184 patients with RA detected enzyme-linked immunosorbent assay. Linear regression analysis, outlier calculations, competition assays...
Abstract Immunogenic responses against citrullinated antigens—proteins post-translationally modified by peptidylarginine deiminase (PAD) enzymes—are hallmark features of rheumatoid arthritis (RA). An important source autoantigens is leukotoxic hypercitrullination (LTH), a form neutrophil cell death wherein membrane perforation results in PAD activation and subsequent widespread citrullination antigens. In RA, proteins can activate autoreactive adaptive immune cells, but their effect on...
Background: Citrullinated proteins are hallmark targets of the autoimmune response in rheumatoid arthritis (RA), 1 but mechanism by which immune tolerance is broken to these self-proteins poorly understood. CD4 + T cells implicated as important drivers due high-affinity, class-switched nature anti-citrullinated protein antibodies (ACPAs) present majority RA patients and prominent genetic contribution certain HLA-DR alleles susceptibility. 2,3 However, precise effect citrullination on MHC...
Abstract Systemic Lupus Erythematosus (SLE) is among the most sex-biased autoimmune diseases identified to date, affecting 9-times more women than men. Recognition of self-RNA by Toll-like receptor 7 (TLR7) implicated as a central pathogenic process leading aberrant production type-I interferon (IFN) in SLE, but specific RNA molecules contributing this have not been defined. Given role and biological sex SLE pathogenesis, we investigated which self-RNAs are potentially responsible for TLR7...
Abstract Cryptic peptides, hidden from the immune system under physiologic conditions, are revealed by changes to MHC class II processing and can facilitate loss of tolerance self-antigens. Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized responses citrullinated self-antigens, in which arginine residues converted citrullines; however, initiating events RA remain poorly understood. We investigated hypothesis that citrullination exposes cryptic epitopes modifying protein...
Abstract Citrullination is recognized as a key pathogenic process in rheumatoid arthritis (RA), evidenced by the formation of anti-citrullinated protein antibodies (APCAs) majority patients; however, mechanisms that result citrullinated autoantigen generation are not fully understood. Although citrullinating enzyme peptidylarginine deiminase IV (PAD4) predominantly expressed neutrophils and monocytes, contribution monocytes to pool has been underexplored. In this study, we utilized multiple...