A5077203387- Inflammatory Bowel Disease
- Viral gastroenteritis research and epidemiology
- T-cell and B-cell Immunology
- Escherichia coli research studies
- Salmonella and Campylobacter epidemiology
- Immune Cell Function and Interaction
- Monoclonal and Polyclonal Antibodies Research
- Microscopic Colitis
- Immunodeficiency and Autoimmune Disorders
- Systemic Lupus Erythematosus Research
- Eosinophilic Esophagitis
- Immunotherapy and Immune Responses
- Cell Adhesion Molecules Research
- Rheumatoid Arthritis Research and Therapies
- Clostridium difficile and Clostridium perfringens research
- Bacteriophages and microbial interactions
- Celiac Disease Research and Management
- Galectins and Cancer Biology
- Transgenic Plants and Applications
- Autoimmune and Inflammatory Disorders
- Glycosylation and Glycoproteins Research
- Helicobacter pylori-related gastroenterology studies
- Psoriasis: Treatment and Pathogenesis
- Lymphoma Diagnosis and Treatment
- Atherosclerosis and Cardiovascular Diseases
Henry M. Jackson Foundation
2017-2025
Walter Reed Army Institute of Research
2023-2025
Naval Medical Research Command
2015-2024
Jackson Foundation
2017-2023
United States Department of the Navy
2019
SUNY Upstate Medical University
2009-2014
Abstract Inflammatory bowel disease (IBD) is characterized by chronic inflammation in the gut. There growing evidence Crohn’s (CD) of existence a preclinical period immunological changes preceding symptom onset that starts years before diagnosis. Gaining insight into this phase will allow prediction and prevention. Analysis serum samples, up to 6 IBD diagnosis (from PREDICTS cohort), revealed identification unique glycosylation signature on circulating antibodies (IgGs) lower galactosylation...
Shigella infections remain endemic in places with poor sanitation and are a leading cause of diarrheal mortality globally, as well major contributor to gut enteropathy stunting. There currently no licensed vaccines for shigellosis but it has been estimated that an effective vaccine could avert 590,000 deaths over 20-year period. A challenge development the low immunogenicity protective efficacy candidate infants young children. Additionally, new might be less immunogenic highly setting...
The Ag receptors on αβ and γδ T cells differ not only in the nature of ligands that they recognize but also their signaling potential. We hypothesized differences αβ- γδTCR signal transduction were due to intracellular pathways coupled these two TCRs. To investigate this, we used transcriptional profiling identify genes encoding molecules are differentially expressed mature cell populations. Unexpectedly, found B lymphoid kinase (Blk), a Src family primarily cells, is cells. Analysis...
Anti-granulocyte macrophage-colony stimulating factor autoantibodies (aGMAbs) are detected in patients with ileal Crohn's disease (CD). Their induction and mode of action during or before not well understood. We aimed to investigate the underlying mechanisms associated aGMAb induction, from functional orientation recognized epitopes, for their impact on intestinal immune homeostasis use as a predictive biomarker complicated CD. characterized using enzyme-linked immunosorbent assay naturally...
Background. Enterotoxigenic E. coli (ETEC) is a principal cause of diarrhea in travelers, deployed military personnel, and children living low to middle-income countries. ETEC expresses variety virulence factors including colonization (CF) that facilitate adherence the intestinal mucosa. We assessed protective efficacy tip-localized subunit CF antigen I (CFA/I), CfaE, delivered intradermally with mutant heat-labile enterotoxin, LTR192G, controlled human infection model (CHIM). Methods. Three...
Enterotoxigenic Escherichia coli (ETEC) cause hundreds of millions cases infectious diarrhea annually, predominantly in children from low-middle income regions. Notably, children, as well volunteers challenged with ETEC, diarrheal severity is significantly increased blood group A (bgA) individuals. EtpA, a secreted glycoprotein adhesin that functions lectin to promote critical interactions between ETEC and glycans on intestinal epithelia for effective bacterial adhesion toxin delivery. EtpA...
BLK, which encodes B lymphoid kinase, was recently identified in genome wide association studies as a susceptibility gene for systemic lupus erythematosus (SLE), and risk alleles mapping to the BLK locus result reduced expression. To determine whether is indeed bona fide gene, we developed an experimental mouse model, namely Blk+/-.lpr/lpr (Blk+/-.lpr) mouse, Blk expression levels are comparable those individuals carrying allele. Here, report that expressed not only cells, but also...
The etiology of Inflammatory Bowel Disease (IBD) remains currently unknown but evidence would suggest that it results from a complex interplay between genetic susceptibility genes, the intestinal microbiome and environment, resulting in an increased response towards microbial self-antigens, followed by development pre-clinical inflammation as precursor to overt clinical disease. Efforts are needed provide insights into characterization disease, possible prediction complications, detection...
Abstract Background Anti-integrin αvβ6 autoantibodies (anti-αvβ6) are present in up to 90% of ulcerative colitis (UC) patients and predate disease development, but there is a paucity data regarding anti-αvβ6 Crohn’s (CD). We hypothesized that would be colonic CD given the shared biological characteristics with UC. Methods measured IgG peripheral blood samples from seven distinct cohorts representing diverse ethnic backgrounds, geographical locations stages including preclinical, incident...
Abstract Background Identification of immune signatures in pre-clinical IBD provides a unique window therapeutic intervention with disease-modifying potential. This study aimed to define the antigen specificities, breadth, longitudinal stability, and predictive ability serum antibody repertoires using novel, high-throughput phage-display immunoprecipitation sequencing assay (PhIP-Seq). Methods Longitudinal samples from active component US military personnel collected at diagnosis ~10, ~4, ~2...
Abstract Heat-labile toxin (LT) from enterotoxigenic Escherichia coli (ETEC) is an important pathogenic protein. Anti-LT antibodies (Abs) induced by vaccination can neutralize the and potentially prevent diarrheal secretion ~ 60% of ETEC strains expressing LT. However, only superficial investigation anti-toxin response usually conducted in clinical trials. Here, we utilized human serum samples two trials performed to assess safety, immunogenicity protection a controlled infection model with...
Blk was identified two decades ago as a B‐cell‐specific member of the Src family tyrosine kinases. Recent studies, however, have discovered that is expressed in many cell types outside B lineage, including early thymic precursors, interleukin‐17‐producing γδ T cells and pancreatic β‐cells. In light these recent discoveries, we performed more comprehensive analysis expression patterns hematopoietic found differentially mature B‐cell subsets, with marginal zone (MZ) expressing high levels, B1...
Campylobacter jejuni polysaccharide capsules (CPS) are characterized by the presence of nonstoichiometric O-methyl phosphoramidate (MeOPN) modifications. The lack stoichiometry is due to phase variation at homopolymeric tracts within MeOPN transferase genes. C. strain 81-176 contains two genes and has been shown previously contain modifications 2 6 positions galactose (Gal) moiety in CPS. We demonstrate here that one transferases, encoded CJJ81176_1435, bifunctional responsible for addition...
Campylobacter jejuni is a leading cause of diarrheal disease worldwide, and currently no preventative interventions are available. C. an invasive mucosal pathogen that has variety polysaccharide structures on its surface, including capsule. In phase 1 studies, capsule conjugate vaccine was safe but poorly immunogenic when delivered alone or with aluminum hydroxide. Here, we report enhanced immunogenicity the liposome adjuvants containing monophosphoryl lipid A without QS-21, known as ALF...
A key aspect to vaccine efficacy is formulation stability. Biochemical evaluations provide information on optimal compositions or thermal stability but are routinely validated by ex vivo analysis and not in animal models. Here we assessed formulations identified improve reduce of the mucosal adjuvant dmLT being investigated polio enterotoxigenic E. coli (ETEC) clinical vaccines. We observed biochemical changes protein with stress, including aggregation subunit dissociation alternatively...
Enterotoxigenic Escherichia coli (ETEC), Campylobacter jejuni (CJ), and Shigella sp. are major causes of bacterial diarrhea worldwide, but there no licensed vaccines against any these pathogens. Most current approaches to ETEC based on recombinant proteins that involved in virulence, particularly adhesins. In contrast, CJ have included conjugate which lipopolysaccharides (LPS) or capsule polysaccharides chemically conjugated proteins. We explored the feasibility developing a multi-pathogen...
Campylobacter species are a leading cause of diarrheal disease globally with significant morbidity. Primary prevention efforts have yielded limited results. Rifaximin chemoprophylaxis decreases rates travelers' diarrhea and may be suitable for high-risk persons. We assessed the efficacy rifaximin in controlled human infection model jejuni.Twenty-eight subjects were admitted to an inpatient facility randomized twice-daily dose 550 mg or placebo. The following day, ingested 1.7 × 105...