A5053941259- Opioid Use Disorder Treatment
- Monoclonal and Polyclonal Antibodies Research
- Immune Cell Function and Interaction
- Substance Abuse Treatment and Outcomes
- Influenza Virus Research Studies
- T-cell and B-cell Immunology
- Immunotherapy and Immune Responses
- Multiple Myeloma Research and Treatments
- Psychiatric care and mental health services
- Bioinformatics and Genomic Networks
- Single-cell and spatial transcriptomics
- Biochemical and Structural Characterization
- Machine Learning in Healthcare
- vaccines and immunoinformatics approaches
- Cell Image Analysis Techniques
- HIV, Drug Use, Sexual Risk
- interferon and immune responses
- Systemic Lupus Erythematosus Research
- Immune Response and Inflammation
- Cytomegalovirus and herpesvirus research
- Health Systems, Economic Evaluations, Quality of Life
- Inflammatory Bowel Disease
- Bacterial Genetics and Biotechnology
- Traffic and Road Safety
- Gene expression and cancer classification
Research Triangle Park Foundation
2025
Icahn School of Medicine at Mount Sinai
2014-2024
Yale University
2024
University of Otago
2024
Bristol-Myers Squibb (United States)
2022-2023
Texas A&M University
2004-2022
University of Dundee
2007-2021
Ninewells Hospital
2007-2019
AkzoNobel (United Kingdom)
2019
Molecular Medicine Ireland
2018
Abstract Secondary use of electronic health records (EHRs) promises to advance clinical research and better inform decision making. Challenges in summarizing representing patient data prevent widespread practice predictive modeling using EHRs. Here we present a novel unsupervised deep feature learning method derive general-purpose representation from EHR that facilitates modeling. In particular, three-layer stack denoising autoencoders was used capture hierarchical regularities dependencies...
Local catabolism of the amino acid tryptophan (Trp) by indoleamine 2,3-dioxygenase (IDO) is considered an important mechanism regulating T cell immunity. We show that IDO transcription was increased when myelin-specific cells were stimulated with tolerogenic altered self-peptides. Catabolites Trp suppressed proliferation and inhibited production proinflammatory helper-1 (T(H)1) cytokines. N-(3,4,-Dimethoxycinnamoyl) anthranilic (3,4-DAA), orally active synthetic derivative metabolite acid,...
Cytomegalovirus infection of young adult humans and mice enhances immune responses to influenza.
Abstract Objective Because rheumatoid arthritis (RA) is a heterogeneous autoimmune disease in terms of manifestations, clinical outcomes, and therapeutic responses, we developed applied novel antigen microarray technology to identify distinct serum antibody profiles patients with RA. Methods Synovial proteome microarrays, containing 225 peptides proteins that represent candidate control antigens, were developed. These arrays used profile autoantibodies randomly selected sera from 2 different...
The bacterial adhesive protein, FimH, is the most common adhesin of Escherichia coli and mediates weak adhesion at low flow but strong high flow. There evidence that this occurs because FimH forms catch bonds, defined as bonds are strengthened by tensile mechanical force. Here, we applied force to single isolated with an atomic microscope in order test directly. If was loaded slowly, broke up (<60 piconewtons rupture force). However, when rapidly, all survived until much higher (140-180...
Summaryγδ T cells contribute uniquely to immune competence. Nevertheless, how they function remains an enigma. It is unclear what most γδ recognize, required for them mount response, and the cell response integrated into host defense. Here, we report that a noted B antigen, algae protein phycoerythrin (PE), murine human antigen. Employing this specificity, demonstrated antigen recognition activated naive make interleukin-17 respond cytokine signals perpetuate response. High frequencies of...
Despite the importance of immune system in many diseases, there are currently no objective benchmarks immunological health. In an effort to identifying such markers, we used influenza vaccination 30 young (20–30 years) and 59 older subjects (60 >89 as models for strong weak responses, respectively, assayed their serological responses strains well a wide variety other parameters, including gene expression, antibodies hemagglutinin peptides, serum cytokines, cell subset phenotypes vitro...
Abstract Objective To evaluate the efficacy and safety of BHT‐3009 in relapsing‐remitting multiple sclerosis (MS) to confirm that causes immune tolerance. Methods is a tolerizing DNA vaccine for MS, encoding full‐length human myelin basic protein. Relapsing‐remitting MS patients were randomized 1:1:1 into three groups: placebo, 0.5mg BHT‐3009, or 1.5mg given intramuscularly at weeks 0, 2, 4, every 4 thereafter until week 44. The primary end point was 4‐week rate occurrence new...
Highlights•We reconstruct regulatory gene networks across seven vascular and metabolic tissues•Integrative analysis using GWASs reveals 30 causally related to CAD•12 CAD-causal are indicated be evolutionarily conserved from mouse•An atherosclerotic arterial wall RNA-processing network affects foam cell formationSummaryInferring molecular can reveal how genetic perturbations interact with environmental factors cause common complex diseases. We analyzed expression data tissues relevant...
Severe forms of inflammatory bowel disease (IBD) that develop in very young children can be caused by variants a single gene. We performed whole-exome sequence (WES) analysis to identify genetic factors might cause granulomatous colitis and severe perianal disease, with recurrent bacterial viral infections, an infant consanguineous parents.We targeted WES DNA collected from the patient her parents. validated our findings similar 150 patients very-early-onset IBD not associated known analyzed...
Increase in global population and growing disease burden due to the emergence of infectious diseases (Zika virus), multidrug-resistant pathogens, drug-resistant cancers (cisplatin-resistant ovarian cancer) chronic (arterial hypertension) necessitate effective therapies improve health outcomes. However, rapid increase drug development cost demands innovative sustainable discovery approaches. Drug repositioning, new or improved by reevaluation approved investigational compounds, solves a...
Abstract Epithelial-to-mesenchymal transition (EMT) is associated with tumor initiation, metastasis, and drug resistance. However, the mechanisms underlying these associations are largely unknown. We studied several types to identify source of EMT gene expression signals a potential mechanism resistance immuno-oncology treatment. Across types, EMT-related was strongly stroma-related genes. Based on RNA sequencing multiple patient-derived xenograft models, enriched in stroma versus...
FimH is a mannose-specific adhesin located on the tip of type 1 fimbriae Escherichia coli that capable mediating shear-enhanced bacterial adhesion. consists fimbria-associated pilin domain and mannose-binding lectin domain, with binding pocket positioned opposite interdomain interface. By using yeast two-hybrid system, purified domains, docking simulations, we show here domains interact one another. The affinity for mannose greatly enhanced (up to 300-fold) in variants which interaction...
<b>Objectives:</b> To identify peripheral blood autoantibody and cytokine profiles that characterise clinically relevant subgroups of patients with early rheumatoid arthritis using antigen microarrays a multiplex assay. <b>Methods:</b> Serum samples from 56 diagnosis <6 months' duration were tested. Cytokine also determined in psoriatic (PsA) ankylosing spondylitis (n = 21), healthy individuals 19). Data analysed Kruskal–Wallis test Dunn's adjustment for multiple comparisons, linear...
Abstract Introduction Anti-citrullinated protein antibodies have a diagnostic role in rheumatoid arthritis (RA); however, little is known about their origins and contribution to pathogenesis. Citrullination the post-translational conversion of arginine citrulline by peptidyl deiminase, increased citrullination proteins observed joint tissue RA brain multiple sclerosis (MS). Methods We applied synovial myelin arrays examine epitope spreading B cell responses citrullinated epitopes both...
<b>Objective</b> To assess predictors of mortality in a population people prescribed methadone. <b>Design</b> Retrospective cohort study. <b>Setting</b> Geographically defined Tayside, Scotland. <b>Participants</b> 2378 and dispensed liquid methadone between January 1993 February 2004. <b>Main outcome measures</b> All cause (primary outcome) drug dependent specific (secondary by means Cox proportional hazards models during 12 years follow-up. <b>Results</b> Overall, 181 (8%) died. Overuse...