A5061635678- HIV Research and Treatment
- Immune Cell Function and Interaction
- Cytomegalovirus and herpesvirus research
- T-cell and B-cell Immunology
- Immunotherapy and Immune Responses
- Immune cells in cancer
- HIV-related health complications and treatments
- interferon and immune responses
- Influenza Virus Research Studies
- HIV/AIDS Research and Interventions
- Gut microbiota and health
- Epigenetics and DNA Methylation
- SARS-CoV-2 and COVID-19 Research
- Virology and Viral Diseases
- vaccines and immunoinformatics approaches
- Diverse Scientific Research Studies
- Tryptophan and brain disorders
- Viral Infections and Immunology Research
- Animal Disease Management and Epidemiology
- Immune Response and Inflammation
- Virus-based gene therapy research
- Inflammasome and immune disorders
- Cytokine Signaling Pathways and Interactions
- Neuroinflammation and Neurodegeneration Mechanisms
- Adipokines, Inflammation, and Metabolic Diseases
Emory University
2021-2025
Case Western Reserve University
2015-2022
Cornell University
2020
University Hospitals of Cleveland
2020
Vaccine & Gene Therapy Institute of Florida
2012-2015
Human immunodeficiency virus (HIV) persistence in latently infected resting memory CD4+ T-cells is the major barrier to HIV cure. Cellular histone deacetylases (HDACs) are important maintaining latency and deacetylase inhibitors (HDACi) may reverse by activating transcription from T-cells. We performed a single arm, open label, proof-of-concept study which vorinostat, pan-HDACi, was administered 400 mg orally once daily for 14 days 20 HIV-infected individuals on suppressive antiretroviral...
Aging leads to dysregulation of multiple components the immune system that results in increased susceptibility infections and poor response vaccines aging population. The dysfunctions adaptive B T cells are well documented, but effect on innate immunity remains incompletely understood. Using a heterogeneous population peripheral blood mononuclear (PBMCs), we first undertook transcriptional profiling found PBMCs isolated from old individuals (≥ 65 years) exhibited delayed altered stimulation...
Highlights•NKT cells promote B cell immunity upon viral infection•NKT are primed by lymph-node-resident macrophages•NKT produce early IL-4 wave at the follicular borders•Early is required for efficient seeding of germinal centersSummaryB constitute an essential line defense from pathogenic infections through generation class-switched antibody-secreting (ASCs) in centers. Although this process known to be regulated helper T (TfH) cells, mechanism which initially seed center reactions remains...
Abstract Age-related alterations in immunity have been linked to increased incidence of infections and decreased responses vaccines the aging population. Human peripheral blood monocytes are known promote Ag presentation antiviral activities; however, impact on monocyte functions remains an open question. We present in-depth global analysis examining classical (CD14+CD16−), intermediate (CD14+CD16+), nonclassical (CD14dimCD16+) monocytes. Monocytes sorted from nonfrail healthy adults (21–40...
HIV-1-specific broadly neutralizing antibodies (bNAbs) can protect rhesus monkeys against simian-human immunodeficiency virus (SHIV) challenge. However, the site of antibody interception and mechanism antibody-mediated protection remain unclear. We administered a fully protective dose bNAb PGT121 to challenged them intravaginally with SHIV-SF162P3. In PGT121-treated animals, we detected low levels viral RNA DNA in distal tissues for seven days following Viral RNA-positive showed...
The RIG-I like receptor pathway is stimulated during RNA virus infection by interaction between cytosolic and viral structures that contain short hairpin dsRNA 5′ triphosphate (5′ppp) terminal structure. In the present study, an agonist of was synthesized in vitro shown to stimulate RIG-I-dependent antiviral responses at concentrations picomolar range. human lung epithelial A549 cells, 5′pppRNA specifically multiple parameters innate response, including IRF3, IRF7 STAT1 activation, induction...
Despite the overwhelming benefits of antiretroviral therapy (ART) in curtailing viral load HIV-infected individuals, ART does not fully restore cellular and humoral immunity. individuals under show reduced responses to vaccination infections are unable mount an effective antiviral immune response upon cessation. Many factors contribute these defects, including persistent inflammation, especially lymphoid tissues, where T follicular helper (Tfh) cells instruct help B launch response. In this...
Human immunodeficiency virus (HIV) persistence during antiretroviral therapy (ART) is associated with heightened plasma interleukin-10 (IL-10) levels and PD-1 expression. We hypothesized that IL-10 blockade would lead to control of viral rebound following analytical treatment interruption (ATI). Twenty-eight ART-treated, simian (SIV)mac
Clinical outcomes are inferior for individuals with HIV having suboptimal CD4 T-cell recovery during antiretroviral therapy (ART). We investigated if the levels of infection and response to homeostatic cytokines subsets contributed divergent reservoir ART by studying virologically-suppressed immunologic responders (IR, achieving a cell count >500 cells/μL on or before two years after initiation), (ISR, did not achieve in first initiation). Compared IR, ISR demonstrated higher HIV-DNA...
People living with HIV (PLWH) who are immune nonresponders (INRs) at greater risk of comorbidity and mortality than responders (IRs) restore their CD4+ T cell count after antiretroviral therapy (ART). INRs have low counts (<350 c/μL), heightened systemic inflammation, increased cycling (Ki67+). Here, we report the findings that memory cells plasma samples from several cohorts enriched in gut-derived bacterial solutes p-cresol sulfate (PCS) indoxyl (IS) both negatively correlated counts. In...
Sex differences play a role in the pathogenesis of number viral diseases. In HIV-1, several studies have reported that chronically infected women significantly lower plasma viremia than men, although exact mechanism by which this occurs has yet to be identified. We performed bulk RNA-seq experiments comparing gene expression between CD4 + T cells from acutely HIV-1–infected men and Zambia, because we observe load (VL) despite higher T-cell activation these during acute/early infection....
<title>Abstract</title> Immunotherapeutic approaches to eliminate latently HIV-infected cells are focused on the adaptive immune system. Herein we provide mechanistic evidence for a molecular cascade characterized by epigenetic reprogramming of innate myeloid and CD4 T cells. The coordinate regulation gene expression mediated transcription factors (TFs) IRF3, IRF7, STAT1 C/EBPβ versus AP-1, promoted development antiviral immunity in these which was associated with control viral load decay...
Significance We characterized the heterogeneity of human TFH cells at a cellular, molecular, functional, and positional level revealed possible mechanistic links between relevant determinants this heterogeneity. Linking topology with specific molecular profile function is key aspect in understanding role particular cell subsets pathogenesis diseases delivery optimal help to GC B for development potent neutralizing antibodies.
Type I IFNs (TI-IFNs) drive immune effector functions during acute viral infections and regulate cell cycling systemic metabolism. That said, chronic TI-IFN signaling in the context of HIV infection treated with antiretroviral therapy (ART) also facilitates persistence, part by promoting immunosuppressive responses CD8+ T exhaustion. To determine whether inhibition IFN-α might provide benefit setting chronic, ART-treated SIV rhesus macaques, we administered an anti-IFN-α antibody followed...
Based on the partial efficacy of HIV/AIDS Thai trial (RV144) with a canarypox vector prime and protein boost, attenuated poxvirus recombinants expressing HIV-1 antigens are increasingly sought as vaccine candidates against HIV/AIDS. Here we describe using systems analysis biological immunological characteristics vaccinia virus Ankara strain Env/Gag-Pol-Nef clade C (referred MVA-C). MVA-C infection human monocyte derived dendritic cells (moDCs) induced expression at high levels from 2 to 8...
The RIG-I like receptor pathway is stimulated during RNA virus infection by interaction between cytosolic and viral structures that contain short hairpin dsRNA 59 triphosphate (59ppp) terminal structure.In the present study, an agonist of was synthesized in vitro shown to stimulate RIG-I-dependent antiviral responses at concentrations picomolar range.In human lung epithelial A549 cells, 59pppRNA specifically multiple parameters innate response, including IRF3, IRF7 STAT1 activation,...
Abstract Antiretroviral therapy (ART) fails to fully restore immune function and is not curative. A single infusion of CCR5 gene-edited autologous CD4 + T cells (SB-728-T) led sustained increases in cell counts, improved homeostasis, reduced the estimated size HIV reservoir. These outcomes were associated with expansion long-term persistence a novel memory stem (CD45RA int RO SCM ) subset that can replenish pool more differentiated cells. We showed CD45RA are transcriptionally distinct from...
<title>Abstract</title> HIV persistence during antiretroviral therapy (ART) is associated with heightened plasma IL-10 levels and the expression of co-inhibitory receptor PD-1. We hypothesized that PD-1 blockade would synergize to boost immune function leading control viral rebound post-analytical treatment interruption (ATI). Twenty-eight ART-treated, SIVmac239-infected rhesus macaques (RMs) were treated anti-IL-10 alone, in combination anti-PD-1 (« combo »), or vehicle. ART was interrupted...