A5089648429- Syphilis Diagnosis and Treatment
- Reproductive tract infections research
- Vector-borne infectious diseases
- Immune Response and Inflammation
- COVID-19 Clinical Research Studies
- Viral Infections and Vectors
- Reproductive System and Pregnancy
- HIV/AIDS Research and Interventions
- Sex work and related issues
- Brucella: diagnosis, epidemiology, treatment
- SARS-CoV-2 and COVID-19 Research
- Virology and Viral Diseases
- Female Genital Mutilation/Cutting Issues
- Kawasaki Disease and Coronary Complications
- HIV Research and Treatment
- interferon and immune responses
- Child and Adolescent Health
- HIV/AIDS drug development and treatment
- Tuberculosis Research and Epidemiology
- HIV, TB, and STIs Epidemiology
- Bacterial Infections and Vaccines
- Mycobacterium research and diagnosis
- Viral gastroenteritis research and epidemiology
- Streptococcal Infections and Treatments
- Inflammasome and immune disorders
Connecticut Children's Medical Center
2015-2025
UConn Health
2013-2025
University of Connecticut
2010-2024
Hartford Financial Services (United States)
2013-2024
Centro Internacional de Entrenamiento e Investigaciones Medicas
2011-2024
Mount Sinai Hospital
2024
Icahn School of Medicine at Mount Sinai
2024
University of Zulia
2014-2023
Hartford Hospital
2021
University of Hartford
2010-2021
The syndrome of periodic fever, aphthous stomatitis, pharyngitis, and cervical adenitis (PFAPA) is the most common fever disease in children. However, pathogenesis unknown. Using a systems biology approach we analyzed blood samples from PFAPA patients whose genetic testing excluded hereditary fevers (HPFs), healthy children pediatric HPF patients. Gene expression profiling could clearly distinguish flares asymptomatic intervals, flares, controls. During attacks, complement (C1QB, C2,...
Most research to understand postacute sequelae of SARS-CoV-2 infection (PASC), or long COVID, has focused on adults, with less known about this complex condition in children. Research is needed characterize pediatric PASC enable studies underlying mechanisms that will guide future treatment.
It is widely believed that innate immune responses to Borrelia burgdorferi (Bb) are primarily triggered by the spirochete's outer membrane lipoproteins signaling through cell surface TLR1/2. We recently challenged this notion demonstrating phagocytosis of live Bb peripheral blood mononuclear cells (PBMCs) elicited greater production proinflammatory cytokines than did equivalent bacterial lysates. Using whole genome microarrays, we show herein that, compared lysates, spirochetes a more...
Phagocytosed Borrelia burgdorferi (Bb) induces inflammatory signals that differ both quantitatively and qualitatively from those generated by spirochetal lipoproteins interacting with Toll-like receptor (TLR) 1/2 on the surface of human monocytes. Of particular significance, in contrast to lipoproteins, internalized spirochetes induce transcription IFN-β. Using inhibitory immunoregulatory DNA sequences (IRSs) specific TLR7, TLR8, TLR9, we show TLR8 inhibitor IRS957 significantly diminishes...
Background The clinical syndrome associated with secondary syphilis (SS) reflects the propensity of Treponema pallidum (Tp) to escape immune recognition while simultaneously inducing inflammation. Methods To better understand duality evasion and in human syphilis, herein we used a combination flow cytometry, immunohistochemistry (IHC), transcriptional profiling study response blood skin 27 HIV(-) SS patients relation spirochetal burdens. Ex vivo opsonophagocytosis assays using syphilitic...
There are currently no validated clinical biomarkers of postacute sequelae SARS-CoV-2 infection (PASC).
We used multiparameter flow cytometry to characterize leukocyte immunophenotypes and cytokines in skin peripheral blood of patients with erythema migrans (EM). Dermal leukocytes were assessed fluids aspirated from epidermal suction blisters raised over EM lesions uninfected controls. Compared corresponding blood, infiltrates enriched for T cells, monocytes/macrophages, dendritic cells (DCs), contained lower proportions neutrophils, virtually devoid B cells. Enhanced expression CD14 HLA-DR by...
ABSTRACT Treponema pallidum reacts poorly with the antibodies present in rabbit and human syphilitic sera, a property attributed to paucity of proteins its outer membrane. To better understand basis for syphilis spirochete's “stealth pathogenicity,” we used dual-label, 3-step amplified assay which treponemes encapsulated gel microdroplets were probed sera parallel anti-FlaA antibodies. A small (approximately 5 10%) but reproducible fraction intact bound IgG and/or IgM Three lines evidence...
ABSTRACT We examined the interactions of live and lysed spirochetes with innate immune cells. THP-1 monocytoid cells were activated to comparable extents by Borrelia burgdorferi B. Treponema pallidum lysates but poorly T. . Because internalized spirochetes, we turned an ex vivo peripheral blood mononuclear cell system that would more closely reflect spirochete-mononuclear phagocyte occur during actual infection. In this system, induced significantly greater monocyte activation inflammatory...
We have previously demonstrated that phagocytosed Borrelia burgdorferi induces activation programs in human peripheral blood mononuclear cells differ qualitatively and quantitatively from those evoked by equivalent lipoprotein-rich lysates. Here we report ingested B. significantly greater transcription of proinflammatory cytokine genes than do lysates live burgdorferi, but not lysate, is avidly internalized monocytes, where the bacteria are completely degraded within phagolysosomes. In...
ABSTRACT Phagocytosed Borrelia burgdorferi (Bb), the Lyme disease spirochete, induces a robust and complex innate immune response in human monocytes, which TLR8 cooperates with TLR2 induction of NF-κB-mediated cytokine production, whereas is solely responsible for transcription IFN-β through IRF7. We now establish role Bb RNA TLR8-mediated IFN-β. First, using TLR2-transfected HEK.293 cells, were unable to phagocytose intact Bb, we observed activation by lipoprotein-rich borrelial lysates...
ABSTRACT The total cellular lipids of Porphyromas gingivalis , a known periodontal pathogen, were previously shown to promote dendritic cell activation and inhibition osteoblasts through engagement Toll-like receptor 2 (TLR2). purpose the present investigation was fractionate all P. define which lipid classes account for TLR2 engagement, based on both in vitro human assays vivo studies mice. Specific serine-containing called 654 430, identified specific high-performance liquid chromatography...
Adherence to combination antiretroviral therapy (ART) has been shown be a determining factor in controlling viral replication, maintaining immunologic function and long-term survival HIV-positive individuals. Little information is available on strategies improve adherence pediatric HIV-infected patients. We conducted randomized, nonblinded, pilot study determine if home-based nursing intervention would medication adherence. The was offered all eligible patients receiving care at Connecticut...
Syphilis is caused by the spirochetal pathogen Treponema pallidum. The local and systemic cellular immune responses elicited bacterium have not been well studied in humans.
Venereal syphilis is a multi-stage, sexually transmitted disease caused by the spirochetal bacterium Treponema pallidum (Tp). Herein we describe cohort of 57 patients (age 18–68 years) with secondary (SS) identified through network public sector primary health care providers in Cali, Colombia. To be eligible for participation, study subjects were required to have cutaneous lesions consistent SS, reactive Rapid Plasma Reagin test (RPR-titer ≥1∶4), and confirmatory treponemal (Fluorescent...
Summary Definitive identification of Treponema pallidum rare outer membrane proteins (OMPs) has long eluded researchers. TP0326, the sole protein in T. with sequence homology to a Gram‐negative OMP, belongs BamA family essential for OM biogenesis. Structural modelling predicted that five polypeptide transport‐associated (POTRA) domains comprise N‐terminus while C‐terminus forms an 18‐stranded amphipathic β‐barrel. Circular dichroism, heat modifiability by SDS‐PAGE, Triton X‐114 phase...
Phagocytosis of Borrelia burgdorferi , the causative agent Lyme disease, is a poorly understood process, despite its importance during host immune response to infection. B. has been shown bind different receptors on surface phagocytic cells, including β 2 integrin, complement receptor 3 (CR3). However, whether these mediate phagocytosis spirochete remains unknown. We now demonstrate that CR3 mediates by murine macrophages and human monocytes. Interaction with integrin not sufficient,...
Antimicrobial peptides (AMPs) are promising candidates to help circumvent antibiotic resistance, which is an increasing clinical problem. Amino-terminal copper and nickel (ATCUN) binding motifs known actively form reactive oxygen species (ROS) upon metal binding. The combination of these two peptidic constructs could lead a novel class dual-acting antimicrobial agents. To test this hypothesis, set ATCUN were screened for their ability induce ROS formation, the most potent then used modify...
Abstract Background Characterization of neutralization antibodies to SARS-CoV-2 infection or vaccination in children and young adults with inflammatory bowel disease (IBD) receiving biologic therapies is crucial. Methods We performed a prospective longitudinal cohort study evaluating spike protein receptor binding domain (S-RBD) IgG positivity along consistent clinical symptoms patients IBD infliximab vedolizumab. Serum was also obtained following immunization approved vaccines. The antibody...
The increase in syphilis rates worldwide necessitates development of a vaccine with global efficacy. We aimed to explore Treponema pallidum subspecies (TPA) molecular epidemiology essential for research by analysing clinical data and specimens from early patients using whole-genome sequencing (WGS) publicly available WGS data.
ABSTRACT Little is known about Zn homeostasis in Yersinia pestis , the plague bacillus. The Znu ABC transporter essential for zinc (Zn) uptake and virulence a number of bacterial pathogens. Bioinformatics analysis identified ZnuABC as only apparent high-affinity system Y. . Mutation znuACB caused growth defect Chelex-100-treated PMH2 medium, which was alleviated by supplementation with submicromolar concentrations Zn. Use transcriptional reporters confirmed that Zur mediated Zn-dependent...