A5078901829- Immune cells in cancer
- Epigenetics and DNA Methylation
- SARS-CoV-2 and COVID-19 Research
- Neuroinflammation and Neurodegeneration Mechanisms
- vaccines and immunoinformatics approaches
- Immune Cell Function and Interaction
- T-cell and B-cell Immunology
- Immune responses and vaccinations
- COVID-19 Clinical Research Studies
- RNA modifications and cancer
- Cytomegalovirus and herpesvirus research
- Single-cell and spatial transcriptomics
- S100 Proteins and Annexins
- Traumatic Brain Injury and Neurovascular Disturbances
- Influenza Virus Research Studies
- Birth, Development, and Health
- Immunotherapy and Immune Responses
National Institute on Aging
2021-2023
Institute on Aging
2022-2023
National Institutes of Health
2022
Tissue-resident macrophages represent a group of highly responsive innate immune cells that acquire diverse functions by polarizing toward distinct subpopulations. The subpopulations reside in skeletal muscle (SKM) and their changes during aging are poorly characterized. By single-cell transcriptomic analysis with unsupervised clustering, we found 11 macrophage clusters male mouse SKM enriched gene expression programs linked to reparative, proinflammatory, phagocytic, proliferative,...
Abstract The resolution of SARS-CoV-2 replication hinges on cell-mediated immunity, wherein CD8 + T cells play a vital role. Nonetheless, the characterization specificity and TCR composition targeting non-spike protein before after infection remains incomplete. Here, we analyzed recognizing six epitopes from nucleocapsid (N) found that slightly increased frequencies N-recognizing but significantly enhanced activation-induced proliferation compared to uninfected donors. N-specific their...
Age-associated DNA methylation in blood cells convey information on health status. However, the mechanisms that drive these changes circulating and their relationships to gene regulation are unknown. We identified age-associated sites six purified blood-borne immune cell types (naive B, naive CD4 + CD8 T cells, granulocytes, monocytes, NK cells) collected from healthy individuals interspersed over a wide age range. Of thousands of sites, only 350 were differentially methylated same direction...
Abstract Background Cytomegalovirus (CMV) infection leads to effector memory CD8 + T cell expansion and is associated with immune dysfunction in older adults. However, the molecular alterations of CMV-specific cells CMV infected healthy young middle-aged adults has not been fully characterized. Results We compared specific for a epitope (pp65 495-503 , NLV) an influenza A virus (IAV) (M1 58-66 GIL) from same serum positive anti-CMV IgG. Compared IAV-specific cells, contained more...
Abstract Nogo‐A, B, and C are well described members of the reticulon family proteins, most known for their negative regulatory effects on central nervous system (CNS) neurite outgrowth repair following injury. Recent research indicates a relationship between Nogo‐proteins inflammation. Microglia, brain's immune cells inflammation‐competent compartment, express Nogo protein, although specific roles in these is understudied. To examine inflammation‐related Nogo, we generated mi...
Abstract COVID-19, caused by SARS-CoV-2 infection, sparked an ongoing global pandemic. While cell-mediated immunity is crucial in mitigating the severity and eradicating viral infections, a comprehensive characterization of CD8+ T cell antigen-specificity, frequency, proliferative capacity, TCR sequences against both COVID-19 vaccinated recovered adults remains incomplete. In this study, we embark on longitudinal analysis circulating cells targeting 10 epitopes from spike (S) protein across...
Abstract Influenza infection remains a leading cause of death among older adults worldwide. While vaccines offer an effective means reducing the severity influenza, their efficacy reduces in this demographic. To gain insight into adaptive immune response, we conducted analysis antigen-specific CD8+ T cells before and after administration high-dose seasonal influenza vaccine (Fluzone) over six seasons (2014, 2018, 2019, 2021, 2022, 2023) cohort healthy (n=37, M=18, F=19, aged 72-92, spanning...
Abstract Tissue-resident macrophages represent a group of highly responsive innate immune cells that acquire diverse functions by polarizing towards distinct subgroups. The subgroups reside in skeletal muscle (SKM) and their changes during aging are poorly characterized. By single-cell transcriptomic analysis, we found mouse SKM primarily comprise two large populations, “healing” LYVE1+ “proinflammatory” LYVE1-macrophages. were further classified into four functional based on the expression...
ABSTRACT Age-associated DNA methylation in blood cells convey information on health status. However, the mechanisms that drive these changes circulating and their relationships to gene regulation are unknown. We identified age-associated sites six purified borne immune cell types (naïve B, naïve CD4 + CD8 T cells, granulocytes, monocytes NK cells) collected from healthy individuals interspersed over a wide age range. Of thousand of sites, only 350 were differentially methylated same...
Abstract COVID-19, an infectious disease caused by SARS-CoV-2, has given rise to the current global pandemic. Despite number of infections reaching over 600 million people worldwide, CD8 +T cells against SARS-CoV-2 in COVID-19 convalescent, vaccinated, and unexposed adults have not been fully characterized. Here, we report frequency, phenotype, vitro expansion capacity circulating recognizing 10 epitopes from spike (S) protein. Through multi-color flow cytometry using antigen-specific...
Abstract Long-term immunity against infections and effective response to vaccination are dependent on unique feature of lymphocytes referred as “memory generation”. Majority our understanding is established murine data human naive memory differentiation limited. In ongoing study we explored epigenetics (DNA methylation accessible chromatin), transcriptomics (basal, activation proliferation induced gene expression), intracellular cytokine assay (high-parameter flow cytometry) B T subsets from...
Abstract The Genetic and Epigenetic Signatures of Translational Aging Laboratory Testing (GESTALT) study is designed to understand the basis immune dysfunction that accompanies human aging. Twelve cell subsets were purified from hundred healthy donors age range 20 – 90 used for transcriptomic, proteomic epigenomic analyses. Additionally, chronic inflammatory components aging assessed by analysis serum cytokines. results first identify cell-specific signatures each omic determine their...
Abstract Long-term immunity against infections and effective response to vaccination are dependent on remarkable unique feature of lymphocytes referred as “memory generation”. Despite having multiple mice studies focused naïve memory transition our understanding human properties is limited. In this study we explored epigenetics (DNA methylation accessible chromatin), transcriptomics activation induced gene expression FACS sorted subsets B, CD4 T CD8 healthy donors from GESTALT cohort. Shared...
Abstract COVID-19, an infectious disease caused by SARS-CoV-2, has given rise to the current global pandemic. Despite number of infections nearing 300 million people worldwide, CD8+ T cells against SARS-CoV-2 in COVID-19 convalescent, vaccinated, and healthy adults their changes with age have not been fully characterized. Here, we report frequency, phenotype, vitro expansion capacity circulating recognizing twenty-two epitopes from five proteins (S, N, M, ORF1ab, ORF3a). Through multi-color...
Abstract COVID-19, an infectious disease caused by SARS-CoV-2, has the current global pandemic. Despite number of infections nearing 100 million people worldwide, CD8+ T cells against SARS-CoV-2 in healthy adults as well convalescent COVID-19 patients are not fully characterized. Here, we report analysis frequency and phenotype circulating recognizing seventeen epitopes from three proteins (S, N, M) HLA-A2+ multi-color flow cytometry with antigen-specific tetramers. Through 65 ranging...