A5066809761- Immune Cell Function and Interaction
- HIV Research and Treatment
- T-cell and B-cell Immunology
- Immunotherapy and Immune Responses
- SARS-CoV-2 and COVID-19 Research
- Diabetes and associated disorders
- CAR-T cell therapy research
- HIV/AIDS Research and Interventions
- COVID-19 Clinical Research Studies
- interferon and immune responses
- Psoriasis: Treatment and Pathogenesis
- COVID-19 diagnosis using AI
- Immune Response and Inflammation
- Immune cells in cancer
- Cancer Immunotherapy and Biomarkers
- Influenza Virus Research Studies
- Machine Learning in Healthcare
- vaccines and immunoinformatics approaches
- Cytokine Signaling Pathways and Interactions
- Immune responses and vaccinations
- HIV-related health complications and treatments
- Animal Virus Infections Studies
- Pancreatic function and diabetes
- Viral gastroenteritis research and epidemiology
- COVID-19 epidemiological studies
Case Western Reserve University
2016-2025
Detroit R&D (United States)
2024
University School
2018-2023
LabCorp (United States)
2022
University of Miami
2022
Children's National
2021
Louis Stokes Cleveland VA Medical Center
2019
Rathenau Instituut
2019
Johnson & Johnson (United States)
2019
Vaccine & Gene Therapy Institute of Florida
2011-2015
Correlates of immune-mediated protection to most viral and cancer vaccines are still unknown. This impedes the development novel incurable diseases such as HIV cancer. In this study, we have used functional genomics polychromatic flow cytometry define signature immune response yellow fever (YF) vaccine 17D (YF17D) in a cohort 40 volunteers followed for up 1 yr after vaccination. We show that immunization with YF17D leads an integrated includes several effector arms innate immunity, including...
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...
ABSTRACT It is not understood how immune inflammation influences the pathogenesis of severe acute respiratory syndrome (SARS). One area strong controversy role interferon (IFN) responses in natural history SARS. The fact that majority SARS patients recover after relatively moderate illness suggests prevailing notion deficient type I IFN-mediated immunity, with hypercytokinemia driving a poor clinical course, oversimplified. We used proteomic and genomic technology to systematically analyze...
Adjuvants are critical for the success of vaccines. Agonists microbial pattern recognition receptors (PRRs) promising new adjuvant candidates. A mechanism through which adjuvants enhance immune responses is to stimulate innate immunity. We studied response in humans synthetic double-stranded RNA (polyinosinic:polycytidylic acid [poly IC] stabilized with poly-l-lysine ICLC]), an agonist toll-like receptor (TLR) 3, and cytosolic helicase MDA-5. Transcriptional analysis blood samples from eight...
In mice, two restricted dendritic cell (DC) progenitors, macrophage/dendritic progenitors (MDPs) and common (CDPs), demonstrate increasing commitment to the DC lineage, as they sequentially lose granulocyte monocyte potential, respectively. Identifying these has enabled us understand role of DCs monocytes in immunity tolerance mice. humans, however, remain unknown. Progress studying human development been hampered by lack an vitro culture system that recapitulates vivo hematopoiesis. Here we...
Significance Pressure overload triggers responses in cardiomyocytes and noncardiomyocytes, leading to pressure hypertrophy (POH). Here, we show that cardiac resident macrophages regulate compensatory myocardial adaptation POH, while nonresident infiltrating are detrimental. At early-phase induces macrophage proliferation, which is regulated by Kruppel-like factor 4. late-phase also Ly6C hi monocyte infiltration, its blockade improves angiogenesis preserves function. Mechanistically, the...
Analysis of the antitumor immune response after gene transfer a foreign major histocompatibility complex class I protein, HLA-B7, was performed. Ten HLA-B7-negative patients with stage IV melanoma were treated in an effort to stimulate local tumor immunity. Plasmid DNA detected within nodules, and RNA encoding recombinant HLA-B7 or protein demonstrated 9 10 patients. T cell migration into lesions observed tumor-infiltrating lymphocyte reactivity enhanced six seven two analyzed, respectively....
Abstract Beginning at the time of insulitis, nonobese diabetic (NOD) mice demonstrate a thymocyte and peripheral T cell proliferative hyporesponsiveness induced by TCR cross-linking, which is associated with reduced IL-2 IL-4 secretion. We previously reported that NOD CD4+ reversed completely in vitro exogenous IL-4, administration to prevents onset insulin-dependent diabetes mellitus (IDDM). This result suggested cell-mediated destruction pancreatic islet beta cells may from regulatory Th2...
West Nile virus (WNV) causes asymptomatic infection in most humans, but for undefined reasons, approximately 20% of immunocompetent individuals develop fever, a potentially debilitating febrile illness, and 1% neuroinvasive disease syndromes. Notably, since its emergence 1999, WNV has become the leading cause epidemic viral encephalitis North America. We hypothesized that CD4+ Tregs might be differentially regulated subjects with symptomatic compared those infection. Here, we show 32 blood...
The molecular events involved in the establishment and maintenance of CD4+ central memory effector T cells (TCM TEM, respectively) are poorly understood. In this study, we demonstrate that ex vivo isolated TCM more resistant to both spontaneous Fas-induced apoptosis than TEM have an increased capacity proliferate persist vitro. Using global gene expression profiling, single cell proteomics, functional assays, show survival depends, at least part, on activation phosphorylation signal...
ABSTRACT How viral and host factors contribute to the severe pathogenicity of H5N1 subtype avian influenza virus infection in humans is poorly understood. We identified three clusters differentially expressed innate immune response genes lungs from (A/Vietnam/1203/04) virus-infected ferrets by oligonucleotide microarray analysis. Interferon were more strongly H5N1-infected ferret than infected with less pathogenic H3N2 subtype. In particular, robust CXCL10 gene expression led us test role...
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...
The Chikungunya virus infection zones have now quickly spread from Africa to parts of Asia, North America and Europe. Originally thought trigger a disease only mild symptoms, recently caused large-scale fatalities widespread economic loss that was linked recent genetic mutation evolution. Due the paucity information on immunological progression, we investigated serum levels 13 cytokines/chemokines during acute phase 6- 12-month post-infection follow-up patients Italian outbreak. We found...
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...
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...
After BNT162b2 messenger RNA vaccination, antibody levels to spike, receptor-binding domain, and virus neutralization were examined in 149 nursing home residents 110 healthcare worker controls. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-naive residents' median post-second vaccine dose titers are one-quarter that of SARS-CoV-2-naive workers.
Immune checkpoint inhibitor (ICI) therapy continues to revolutionize melanoma treatment, but only a subset of patients respond. Major efforts are underway develop minimally invasive predictive assays ICI response. Using single-cell transcriptomics, we discovered unique CD8 T cell blood/tumor-shared subpopulation in with high levels oxidative phosphorylation (OXPHOS), the ectonucleotidases CD38 and CD39, both exhaustion cytotoxicity markers. We called this population OXPHOS “CD8+ TOXPHOS...
Nursing home (NH) residents have borne a disproportionate share of SARS-CoV-2 morbidity and mortality. Vaccines limited hospitalisation death from earlier variants in this vulnerable population. With the rise Omicron future variants, it is vital to sustain broaden vaccine-induced protection. We examined effect boosting with BNT162b2 mRNA vaccine on humoral immunity Omicron-specific neutralising activity among NH healthcare workers (HCWs). longitudinally enrolled 85 (median age 77) 48 HCWs...