A5002268030- Telomeres, Telomerase, and Senescence
- DNA Repair Mechanisms
- Genetics, Aging, and Longevity in Model Organisms
- T-cell and B-cell Immunology
- Chromosomal and Genetic Variations
- Genomics and Chromatin Dynamics
- Immune Cell Function and Interaction
- Monoclonal and Polyclonal Antibodies Research
- Microtubule and mitosis dynamics
- Cancer-related Molecular Pathways
- Animal Genetics and Reproduction
- Fungal and yeast genetics research
- CRISPR and Genetic Engineering
- Melanoma and MAPK Pathways
- Wound Healing and Treatments
- Sarcoma Diagnosis and Treatment
- Immunodeficiency and Autoimmune Disorders
- Cancer Research and Treatments
- Retinal Development and Disorders
- Synthesis and biological activity
- Bioinformatics and Genomic Networks
- Gene expression and cancer classification
- Nuclear Structure and Function
- Cytomegalovirus and herpesvirus research
- SARS-CoV-2 and COVID-19 Research
Cardiff University
2012-2023
University of Surrey
2021-2023
Cancer Genetics (United States)
2019
University of Sussex
2014
The University of Texas MD Anderson Cancer Center
2010
Biomedical Research Foundation of the Academy of Athens
2010
University Medical Center
2010
Fox Chase Cancer Center
2010
University of Pennsylvania
2010
University of Wales
1998-2009
Older people suffer from a decline in immune system, which affects their ability to respond infections and raise efficient responses vaccines. Effective specific antibodies older individuals are decreased favour of non-specific antibody production. We investigated the B-cell repertoire DNA samples peripheral blood aged 86-94 years, control group 19-54 using spectratype analysis IGHV complementarity determining region (CDR)3. found that proportion had dramatic collapse diversity. Sequencing...
Significance Antibodies are selected to bind microbial but not self-antigens, because binding self would compete with microbes, shorten antibody half-life, and cause autoimmunity. Self-tolerance is actively acquired in part by discarding self-binding antibodies before the body exposed a microbe or vaccine. The experiments here provide evidence of an opposite mechanism, allowing that initially both foreign self-antigens acquire self/non-self discrimination during course immune response...
Persistent viral infections and inflammatory syndromes induce the accumulation of T cells with characteristics terminal differentiation or senescence. However, mechanism that regulates end-stage these is unclear. Human CD4(+) effector memory (EM) (CD27(-)CD45RA(-)) also EM re-express CD45RA (CD27(-)CD45RA(+); EMRA) have many differentiation. These include expression surface KLRG1 CD57, reduced replicative capacity, decreased survival, high nuclear γH2AX after TCR activation. A paradoxical...
CD27 expression has been used to distinguish between memory and naive B cells in humans. However, low levels of mutated isotype-switched CD27-IgD- are seen healthy adults, these increased some autoimmune diseases the elderly. Thus is not a universal marker Various hypotheses have put forward as function CD27- population. Since we previously found high throughput IGHV repertoire analysis useful "innate-like" (CD27+IgD+), employed similar analyses elucidate relationship CD27+ cells. IgM+IgD-...
It is well known that older people are more susceptible to morbidity and mortality from infectious diseases, particularly pulmonary diseases such as pneumococcal pneumonia where vaccines do not provide efficient protection in younger populations. We have previously shown the B-cell repertoire old reduced hypothesise this may contribute impaired humoral responses of elderly. Here, we investigated antibody winter vaccination two age groups, aged 18-49 65-89. found serum IgM IgA were...
On April 7,8, 2009 a Symposium entitled "Pathophysiology of Successful and Unsuccessful Ageing" took place in Palermo, Italy. Here, the lectures G. Pawelec, D. Dunn-Walters and. Colonna-Romano on T B immunosenescence are summarized. In elderly, many alterations both innate acquired immunity have been described. Alterations to immune system older person generally viewed as deterioration immunity, leading use catch-all term immunosenescence. Indeed, immunological parameters often markedly...
Senescent cells show an altered secretome profile termed the senescence-associated secretory phenotype (SASP). There is increasing body of evidence that suggests accumulation SASP-positive senescent in humans partially causal observed shift to a low-level pro-inflammatory state aged individuals. This turn SASP as possible therapeutic target ameliorate inflammatory conditions elderly, and thus better understanding signalling pathways underlying are required. Prior studies using early...
From paired blood and spleen samples from three adult donors, we performed high-throughput VH sequencing of human B cell subsets defined by IgD CD27 expression: IgD(+)CD27(+) ("marginal zone [MZ]"), IgD(-)CD27(+) ("memory," including IgM ["IgM-only"], IgG IgA) IgD(-)CD27(-) cells ("double-negative," IgM, IgG, IgA). A total 91,294 unique sequences clustered in 42,670 clones, revealing major clonal expansions each these subsets. Among further analyzed those shared different or tissues for gene...
Telomeres play a key role in upholding the integrity of genome, and telomerase expression spermatogonial stem cells is responsible for maintenance telomere length human male germline. We have previously described extensive allelic variation somatic cell that set zygote, ultimate source which may be This implies despite activity, substantial can generated tolerated germline; order to investigate this further, we examined nature Here, describe an analysis both genome-wide single molecule...
Tissue transglutaminase (TG2) affects cell-matrix interactions in cell spreading, migration and extracellular matrix (ECM) reorganisation. Using fibroblasts deficient TG2 or overexpressing normal crosslinking-deficient enzyme, we show that the crosslinking activity intracellular G-protein function signal transduction contribute differentially to regulation of interactions. TG2-deficient cells displayed attachment but delayed spreading on ECM substrata defects motility unrelated crosslinking....
Abstract Conventional studies of brain changes in normal aging have concentrated on gray matter as the locus for cognitive dysfunction. However, there is accumulating evidence from rhesus monkey that white may be a more critical factor decline. Such include ultrastructural and biochemical myelin breakdown with age, well recent magnetic resonance imaging global loss forebrain volume diffusion tension increased diffusivity matter. Moreover, many these correlate age‐related Based diverse...
Single telomere length analysis (STELA) of the XpYp has revealed extensive allelic variation and ultra-short telomeres in senescent cells. Superimposed on end-replication losses are additional mutational events that result large-scale changes length. In order to establish if dynamics typical human telomeres, here we describe an using STELA 2p, 11q, 12q, 17p XpYp. The loss (erosion rates stochastic changes) was conserved among 12q within same cell strains dependent replicative kinetics cells...
Immune protection against pulmonary infections, such as seasonal flu and invasive pneumonia, is severely attenuated with age, vaccination regimes for the elderly people often fail to elicit effective immune responses. We have previously shown that influenza pneumococcal vaccine responses in older population are significantly impaired terms of serum antibody production, repertoire differences by CDR-H3 spectratype analysis. Here we report a detailed analysis B cell response vaccine, including...
DNA repair mechanisms are fundamental for B cell development, which relies on the somatic diversification of immunoglobulin genes by V(D)J recombination, hypermutation, and class switch recombination. Their failure is postulated to promote genomic instability malignant transformation in cells. By performing targeted sequencing 73 key 29 lymphoma samples, germline mutations were identified various pathways, mainly diffuse large lymphomas (DLBCLs). Mutations mismatch (EXO1, MSH2, MSH6)...