A5039934564- T-cell and B-cell Immunology
- Immune Cell Function and Interaction
- Immunotherapy and Immune Responses
- CAR-T cell therapy research
- Adipokines, Inflammation, and Metabolic Diseases
- Monoclonal and Polyclonal Antibodies Research
- Regulation of Appetite and Obesity
- DNA Repair Mechanisms
- Single-cell and spatial transcriptomics
- Adipose Tissue and Metabolism
- Neuroinflammation and Neurodegeneration Mechanisms
- Immunodeficiency and Autoimmune Disorders
- Biochemical Analysis and Sensing Techniques
- Genetics, Aging, and Longevity in Model Organisms
- Ubiquitin and proteasome pathways
- Telomeres, Telomerase, and Senescence
- Cytomegalovirus and herpesvirus research
- Immune cells in cancer
- Optimism, Hope, and Well-being
- Cell death mechanisms and regulation
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Educational Practices and Sociocultural Research
- Axon Guidance and Neuronal Signaling
- Effects of Radiation Exposure
- Virus-based gene therapy research
National Institutes of Health
2002-2022
National Institute on Aging
2008-2022
MRC Laboratory of Molecular Biology
2014
Institute on Aging
2007-2012
National Institute on Drug Abuse
2010
Laboratory of Molecular Genetics
2009
University of Maryland, Baltimore
2000
National Cancer Institute
1996
Science Applications International Corporation (United States)
1996
Stony Brook University
1987-1988
We present the AGEMAP (Atlas of Gene Expression in Mouse Aging Project) gene expression database, which is a resource that catalogs changes as function age mice. The database includes for 8,932 genes 16 tissues age. found great heterogeneity amount transcriptional with different tissues. Some displayed large differences old mice, suggesting these may contribute strongly to organismal decline. Other showed few or no age, indicating strong levels homeostasis throughout life. Based on pattern...
Alterations in the number and composition of lymphocytes their subsets blood are considered a hallmark immune system aging. However, it is unknown whether rates change stable or with age, inter-individual variations lymphocyte over time undergo different at ages. Here, we report longitudinal analysis T- B-cells subsets, NK cells 165 subjects aged from 24 to 90 years, each subject assessed baseline an average 5.6 years follow-up.The T-(CD4(+) CD8(+)) B-cells, were relative throughout adult...
Abstract The decline of CD8 + T cell functions contributes to deteriorating health with aging, but the mechanisms that underlie this phenomenon are not well understood. We use single-cell RNA sequencing both cross-sectional and longitudinal samples assess how human heterogeneity transcriptomes change over nine decades life. Eleven subpopulations cells their dynamic changes age identified. Age-related in gene expression result from percentage expressing a given transcript, quantitative...
The pp60c-src protein that is expressed at high levels in cultures of neurons from rat embryos displays an altered mobility on SDS-polyacrylamide gels due to a structural difference the amino-terminal region molecule. In this report we show expression unique form pp60c-src, designated pp60c-src(+), not restricted cultured neuronal cells since molecules tissues avian and neural also display retarded electrophoretic mobility. pp60c-src(+) was found contain novel phosphorylated tryptic peptide...
A number of biological parameters have been cited as hallmarks immune aging. However, it is not clear whether these multiple changes are the result common underlying aging processes and follow correlated trajectories, or patterns change for vary across individuals reflect heterogeneity in process. Here, we studied system through longitudinal analysis telomere length, inflammatory cytokines, antibody titer to CMV 465 subjects ranging age from 21 88 at first visit, with an average 13 years...
IgH and L chain transgenes encoding a phosphocholine (PC)-specific Ig receptor were introduced into recombinase-activating gene (Rag-2-/-) knockout mice. The PC-specific B cells that developed behaved like known autoreactive lymphocytes. They 1) developmentally arrested in the bone marrow, 2) unable to secrete Ab, 3) able escape clonal deletion develop B1 peritoneal cavity, 4) rescued by overexpression of bcl-2. A second IgL was genetically Rag-2-/- mice expressing receptor. These dual...
Ionizing radiation (IR) is a major source of cellular damage and the immediate response to IR has been well characterized. But long-term impact on cell function its relationship with aging are not known. Here, we examined effects telomere length other biomarkers 50 68 years post-exposure (two time points per person) in survivors atomic bombing at Hiroshima during WWII. We found that leukocytes was inversely correlated dose (p=0.008), this effect primarily who were exposed younger ages;...
Phosphocholine (PC) is the immunodominant epitope found on surface of Streptococcus pneumoniae (SPn). T15-idiotype Abs, whose heavy (H) chain variable region encoded by V1 gene, are dominant in anti-PC response adult mice and protect from lethal pneumococcal infection. The ability Abs using H chains other than to against infection remains controversial. We generated V1(-/-) knockout determine whether protective could be produced absence gene. No were immunized with avirulent SPn; however,...
The decline in adaptive immunity, naïve T-cell output and a contraction the peripheral T cell receptor (TCR) repertoire with age are largely attributable to thymic involution loss of critical cytokines hormones within microenvironment.To assess molecular changes associated this function, we used cDNA microarray analyses examine transcriptomes thymocytes from mice various ages ranging very young (1 month) old (24 months).Genes biological processes including oxidative phosphorylation, T-and...
Thymic atrophy occurs during normal aging, and is accelerated by exposure to chronic stressors that elevate glucocorticoid levels impair the naïve T cell output. The orexigenic hormone ghrelin was recently shown attenuate age‐associated thymic atrophy. Here, we report enhances proliferation of murine CD4+ primary cells a T‐cell line. Ghrelin induced activation ERK1/2 Akt signaling pathways, via upstream phosphatidylinositol‐3‐kinase protein kinase C, enhance proliferation. Moreover,...
Recent research has proposed that GIT2 (G protein-coupled receptor kinase interacting protein 2) acts as an integrator of the aging process through regulation 'neurometabolic' integrity. One commonly accepted hallmarks is thymic involution. At a relatively young age, 12 months old, GIT2-/- mice present prematurely distorted structure and dysfunction compared to age-matched month-old wild-type control (C57BL/6) mice. Disruption in (GIT2KO) was associated with significant reduction expression...
Abstract Stimulation of human primary T cells with immobilized anti-CD3 and anti-CD28 Abs in vitro provide a system to study cell activation proliferation an avenue for expanding immunotherapy. Magnetic beads conjugated (Dynabeads Human T-Activator [D-TCA]) have been golden standard stimulating vitro. In this study, we report that application using on lipid microbubbles (microbubble-based activator [MB-TCA]) stimulate naive resulted expansion superior D-TCA. 56-d cultures three repeated...
A point mutation in the pleckstrin homology domain of mouse Bruton's tyrosine kinase (btk) gene results an X-linked immune defect, Xid, characterized by immunologic unresponsiveness to polymeric carbohydrate Ags. In Xid mice, B cells specific for phosphocholine (PC) do not develop peripheral lymphoid tissues because they either fail be positively selected from marrow or are clonally deleted via Ag-driven, receptor-mediated process. Overexpression bcl-2 allows PC-specific survive and mature...
Abstract Cultures of neurons from rat embroyos have been show previously to express high levels a unique pp 60c‐ src [Brugge et al (1985): Nature 316:524‐526], the cellular homologue transforming protien Rous sarcoma virus. This altered form (+), designated displays retarded electroretic mobility due structural alteration within aminoterminal region molecule al, 1985]. In order investigate distribution and possible role (+) in intact brain, we examined expression extracts developing...
Abstract DNA damage is a prominent biomarker for numerous diseases, including cancer, as well the aging process. Detection of routinely relies on traditional microscopy or cytometric methods. However, these techniques are typically limited throughput and not ideally suited large-scale longitudinal population studies that require analysis large sample sets. We have developed HiIDDD (High-throughput Immune cell Damage Detection), robust, quantitative single-cell assay measures by...
T15i knockin (KI) mice express a H chain that is encoded by rearranged T15 VDJ transgene which has been inserted into the J(H) region of chromosome 12. This T15H combines with kappa22-33 L to produce T15-Id+ Ab having specificity for phosphocholine (PC). Inasmuch as Abs dominate primary immune response PC in normal mice, it was surprising find 80% PC-dextran-binding B cells unimmunized homozygous KI were T15-Id-. Analysis chains expressed these T15-Id-, PC-specific revealed two chains,...
We present the AGEMAP (Atlas of Gene Expression in Mouse Aging Project) gene expression database, which is a resource that catalogs changes as function age mice. The database includes for 8,932 genes 16 tissues age. found great heterogeneity amount transcriptional with different tissues. Some displayed large differences old mice, suggesting these may contribute strongly to organismal decline. Other showed few or no age, indicating strong levels homeostasis throughout life. Based on pattern...
The majority of anti-phosphocholine (PC) antibodies induced by the PC epitope in Proteus morganii (PM) express M603 idiotype (id), which is characterized an invariant Asp to Asn substitution at V(H):D(H) junction. To elucidate molecular basis M603-like B cells acquire mutations resulting this substitution, we analyzed immune response PC-PM terminal deoxynucleotidyl transferase (TdT) gene knockout (KO) mice. In absence TdT, T15-id comprised 80-100% primary PC-PM. Less than 10% wild-type mice...