A5067993496- Telomeres, Telomerase, and Senescence
- Acute Myeloid Leukemia Research
- Immune Cell Function and Interaction
- Hematopoietic Stem Cell Transplantation
- Epigenetics and DNA Methylation
- Myeloproliferative Neoplasms: Diagnosis and Treatment
- Chronic Myeloid Leukemia Treatments
- CAR-T cell therapy research
- Chronic Lymphocytic Leukemia Research
- Cytomegalovirus and herpesvirus research
- DNA Repair Mechanisms
- Blood disorders and treatments
- Cancer Immunotherapy and Biomarkers
- Hematological disorders and diagnostics
- Cancer Cells and Metastasis
- Single-cell and spatial transcriptomics
- Mesenchymal stem cell research
- Renal and related cancers
- RNA modifications and cancer
- Erythrocyte Function and Pathophysiology
- Immune cells in cancer
- Immunodeficiency and Autoimmune Disorders
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- T-cell and B-cell Immunology
- Skin Protection and Aging
RWTH Aachen University
2016-2025
Universitätsklinikum Aachen
2014-2024
University Hospital Cologne
2021-2024
University Medical Center Freiburg
2022-2023
Universität Hamburg
2023
University Medical Center Hamburg-Eppendorf
2023
Integrated Oncology (United States)
2023
Heinrich Heine University Düsseldorf
2022
Düsseldorf University Hospital
2022
Spanish National Cancer Research Centre
2011-2015
Abstract Background Human aging is associated with DNA methylation changes at specific sites in the genome. These epigenetic modifications may be used to track donor age for forensic analysis or estimate biological age. Results We perform a comprehensive of profiles narrow down 102 age-related CpG blood. demonstrate that most these age-associated are reversed induced pluripotent stem cells (iPSCs). Methylation levels three CpGs - located genes ITGA2B , ASPA and PDE4C were subsequently...
We investigate the in vivo patterns of stem cell divisions human hematopoietic system throughout life. In particular, we analyze shape telomere length distributions underlying behavior within individuals. Our mathematical model shows that these contain a fingerprint progressive loss and fraction symmetric proliferations. predictions are tested against measured humans across all ages, collected from lymphocyte granulocyte sorted data 356 healthy individuals, including 47 cord blood 28 bone...
Abstract T-cell prolymphocytic leukemia (T-PLL) is a rare and poor-prognostic mature malignancy. Here we integrated large-scale profiling data of alterations in gene expression, allelic copy number (CN), nucleotide sequences 111 well-characterized patients. Besides prominent signatures activation prevalent clonal variants, also identify novel hot-spots for CN variability, fusion molecules, alternative transcripts, progression-associated dynamics. The overall lesional spectrum T-PLL mainly...
Current US Food and Drug Administration-approved chimeric antigen receptor (CAR) T cells harbor the cell (TCR)-derived ζ chain as an intracellular activation domain in addition to costimulatory domains. The functionality a CAR format of other chains TCR complex, namely CD3δ, CD3ε CD3γ, instead ζ, remains unknown. In present study, we have systematically engineered new CD3 CARs, each containing only one We found that CARs or CD3γ cytoplasmic tails outperformed conventional vivo....
Abstract Background The search for biomarkers to identify suitable candidates immune checkpoint inhibitor (ICI) therapy remains ongoing. We evaluate how soluble levels of the next generation Lymphocyte Activation Gene-3 (sLAG-3) and its association with circulating T lymphocyte subsets could pose as a novel biomarker predict outcome ICI therapy. Methods Circulating sLAG3 were analyzed using multiplex immunoassay in n = 84 patients undergoing advanced solid cancer, accompanied by flow...
Infiltration by macrophages represents a characteristic morphological hallmark in high-grade lymphatic malignancies such as Burkitt's lymphoma (BL). Although can, principle, target neoplastic cells and mediate antibody-dependent cellular cytotoxicity (ADCC), tumor-associated (TAMs) regularly fail to exert direct cytotoxic functions. The underlying mechanisms responsible for this observation remain unclear. We demonstrate that inflammatory M1 kill proliferating B cell releasing the...
Aplastic anemia is a rare but life-threatening disorder characterized by cytopenia in at least two of the three blood lineages. A frequent feature patients with aplastic that they have shorter telomeres than those age-matched controls. Testosterone has been used for over half century treatment anemia. However, although remissions are following hormone therapy, molecular mechanism underlying response to remained unknown. Here we explored possibility recently described regulation telomerase...
Senolytic drugs are thought to target senescent cells and might thereby rejuvenate tissues. In fact, such compounds were suggested increase health lifespan in various murine aging models. So far, effects of senolytic have not been analysed during replicative senescence human mesenchymal stromal (MSCs). this study, we tested four potentially drugs: ABT-263 (navitoclax), quercetin, nicotinamide riboside, danazol. The these long-term expansion MSCs, until senescence. Furthermore, determined the...
The bone marrow niche has a pivotal role in progression, survival, and drug resistance of multiple myeloma cells. Therefore, it is important to develop means for targeting the microenvironment. Myeloma-associated macrophages (MAM) are M2 like. They provide nurturing signals cells promote immune escape. Reprogramming M2-like toward tumoricidal M1 phenotype represents an intriguing therapeutic strategy. This especially interesting view successful use mAbs against cells, as these therapies hold...
Human telomere biology disorders (TBD)/short syndromes (STS) are heterogeneous caused by inherited loss-of-function mutations in telomere-associated genes. Here, we identify 3 germline heterozygous missense variants the RPA1 gene 4 unrelated probands presenting with short telomeres and varying clinical features of TBD/STS, including bone marrow failure, myelodysplastic syndrome, T- B-cell lymphopenia, pulmonary fibrosis, or skin manifestations. All cluster to DNA-binding domain A protein. is...
Biallelic germline ERCC6L2 variants strongly predispose to bone marrow failure (BMF) and myeloid malignancies characterized by somatic TP53-mutated clones erythroid predominance. We present a series of 52 subjects (35 families) with biallelic collected retrospectively in 11 centers globally, including follow-up 1165 person-years. At initial investigations, 32 individuals were diagnosed BMF 15 hematological malignancy (HM). Subjects presented 19 different across ERCC6L2, we identified founder...
Primary cells enter replicative senescence after a limited number of cell divisions. This process needs to be considered in culture experiments, and it is particularly important for regenerative medicine. Replicative associated with reproducible changes DNA methylation (DNAm) at specific sites the genome. The mechanism that drives senescence-associated DNAm remains unknown - may involve stochastic drift due imperfect maintenance epigenetic marks or directly regulated In this study, we...
Studies in which mesenchymal stromal cells (MSC) from the placenta are compared with multiple MSC types other sources rare. The chorionic plate of human is mainly composed fetal blood vessels embedded stroma tissue, lined by trophoblastic and organized into villi (CV) structures. We comprehensively characterized collected postnatal (CV-MSC) analyzing their growth proliferation potential, differentiation, immunophenotype, extracellular matrix production, telomere length, aging phenotype,...
Polychlorinated biphenyls (PCBs) are organochlorine pollutants with a worldwide dissemination. We examined telomere length (TL) in peripheral blood cells of 207 individuals high body burden PCBs due to occupational exposure transformer recycling company. Whereas TL granulocytes was not affected, the age-adjusted lymphocytes (∆TLLymph) exposed significantly shorter than expected [-0.77 kb; 95 % confidence interval (CI) -0.9316; -0.6052; p = 0.0001]. PCB did affect lymphocyte numbers or T cell...
Age is a major risk factor for severe outcome of the 2019 coronavirus disease (COVID-19). In this study, we followed hypothesis that particularly patients with accelerated epigenetic age are affected by outcomes COVID-19. We investigated various DNA methylation datasets blood samples aging signatures and performed targeted bisulfite amplicon sequencing. Overall, clocks closely correlated chronological patients, either or without acute respiratory distress syndrome. Furthermore, lymphocytes...
Background Atrial fibrillation (AF) is the most common cardiac arrhythmia with a massive burden on global health. The prevalence of AF increases dramatically age and can be up to 18% in patients older than 80 years. Telomeres, which are short, repeated DNA sequences at end chromosomes, known act as biological aging marker. In this study, we investigated relation telomere shortening context atrial remodeling. Furthermore, assessed changes gene expression profiles according length (TL) left...
Pathogenic germline variants affecting proper telomere maintenance result in premature shortening and cause biology disorders (TBDs). While classical dyskeratosis congenita children is rather well defined, late-onset ("cryptic") TBDs remain underrecognized, resulting underdiagnosis inadequate treatment affected adults. Here, we present a series of adult TBD cases collected through the German reference center between 2014 2024. Patients ≥18 years with an age-matched length (TL) < 10th...
Despite being overexpressed in different tumor entities, RIO kinases are hardly characterized mammalian cells. We investigated the role of these atypical cancer Using isogenic colon-, breast- and lung cell lines, we demonstrate that knockdown RIOK1, but not RIOK2 or RIOK3, strongly impairs proliferation invasiveness conventional 3D culture systems. Interestingly, effects were mainly observed RAS mutant In contrast, growth wildtype Caco-2 Bcr-Abl-driven K562 cells is affected by RIOK1...