A5033742662- Glioma Diagnosis and Treatment
- Genomics and Chromatin Dynamics
- Neuroinflammation and Neurodegeneration Mechanisms
- Epigenetics and DNA Methylation
- Immune cells in cancer
- Single-cell and spatial transcriptomics
- RNA Research and Splicing
- Cancer-related molecular mechanisms research
- Gene expression and cancer classification
- Immune Cell Function and Interaction
- CRISPR and Genetic Engineering
- Cytokine Signaling Pathways and Interactions
- RNA modifications and cancer
- Spaceflight effects on biology
- Cancer Cells and Metastasis
- Histone Deacetylase Inhibitors Research
- Cancer Mechanisms and Therapy
- Molecular Biology Techniques and Applications
- Ferroptosis and cancer prognosis
- Cancer-related Molecular Pathways
- RNA and protein synthesis mechanisms
- Health, Environment, Cognitive Aging
- Neurogenesis and neuroplasticity mechanisms
- T-cell and B-cell Immunology
- Immunotherapy and Immune Responses
Instytut Biologii Doświadczalnej im. Marcelego Nenckiego
2013-2024
Polish Academy of Sciences
2013-2024
Gdańsk Medical University
2021-2024
Massachusetts General Hospital
2016-2023
Institute of Neurobiology
2018
Harvard University
2016-2017
Gene Therapy Laboratory
2012
Abstract Microglia are resident myeloid cells in the central nervous system (CNS) that control homeostasis and protect CNS from damage infections. peripheral accumulate adapt tumor supporting roles human glioblastomas show prevalence men. Cell heterogeneity functional phenotypes of subpopulations gliomas remain elusive. Here we single-cell RNA sequencing (scRNA-seq) CD11b + naïve GL261 glioma-bearing mice reveal distinct profiles microglia, infiltrating monocytes/macrophages...
Chromatin accessibility plays a fundamental role in gene regulation. Nucleosome placement, usually measured by quantifying protection of DNA from enzymatic digestion, can regulate accessibility. We introduce metric that uses micrococcal nuclease (MNase) digestion novel manner to measure chromatin combining information several digests increasing depths. This metric, MACC (MNase accessibility), quantifies the inherent heterogeneity nucleosome which some nucleosomes are seen preferentially at...
Most neurological diseases are associated with chronic inflammation initiated by the activation of microglia, which produce cytotoxic and inflammatory factors. Signal transducers activators transcription (STATs) potent regulators gene expression but contribution particular STAT to STAT-dependent transcriptional networks underlying brain need be identified. In present study, we investigated genomic distribution Stat binding sites role Stats in lipopolysaccharide (LPS)-activated primary...
The organization of DNA into chromatin is dynamic; nucleosomes are frequently displaced to facilitate the ability regulatory proteins access specific elements. To gain insight nucleosome dynamics, and follow how dynamics change during differentiation, we used a technique called time-ChIP quantitatively assess histone H3.3 turnover genome-wide differentiation mouse ESCs. We found that, without prior assumptions, high could be identify regions involved in gene regulation. High was seen at...
Activation of transcription requires alteration chromatin by complexes that increase the accessibility nucleosomal DNA. Removing nucleosomes from regulatory sequences has been proposed to play a significant role in activation. We tested whether changes nucleosome occupancy occurred on set genes is activated unfolded protein response (UPR). observed no decrease most promoters, gene bodies, and enhancers. Instead, there was an nucleosomes, as measured micrococcal nuclease (MNase) digestion...
Male sex is a risk factor for colorectal cancer (CRC) with higher illness burden and earlier onset. Thus, we hypothesized that loss of chromosome Y (LOY) in the tumor micro-environment (TME) might be involved oncogenesis. Previous studies show LOY circulating leukocytes aging men was associated shorter survival non-hematological cancer, as well CD4 + T-lymphocytes prostate vs. controls. However, nothing known about infiltrating TME address this aspect here. We studied frequency functional...
Glioblastoma (GBM) is the most aggressive primary brain tumor, with ineffective anti-tumor responses and a poor prognosis despite treatments. GBM immune microenvironment heterogenous activation of specific populations in not fully characterized. Reliable animal models are critical for defining mechanisms immunity. First we analyzed subpopulations present rat C6 gliomas. Using flow cytometry determined kinetics infiltration myeloid cells T lymphocytes into glioma-bearing brains. We found...
The reduced ability of the central nervous system to regenerate with increasing age limits functional recovery following demyelinating injury. Previous work has shown that myelin debris can overwhelm metabolic capacity microglia, thereby impeding tissue regeneration in aging, but underlying mechanisms are unknown. In a model demyelination, we found substantial number genes were not effectively activated aged myeloid cells displayed epigenetic modifications associated restricted chromatin...
// Jakub Mieczkowski 1, * , Marta Kocyk 2, Pawel Nauman 3 Konrad Gabrusiewicz 1 Małgorzata Sielska Piotr Przanowski Maleszewska Wenson D. Rajan Dominika Pszczolkowska Tomasz Tykocki Wieslawa Grajkowska 4 Katarzyna Kotulska 5 Marcin Roszkowski 6 Boguslaw Kostkiewicz 7 Bozena Kaminska Laboratory of Molecular Neurobiology, Nencki Institute Experimental Biology, Warsaw, Poland 2 Postgraduate School Medicine, Medical University Department Neurosurgery, Psychiatry and Neurology, Departments...
In glioma, microglia and infiltrating macrophages are exposed to factors that force them produce cytokines chemokines, which contribute tumor growth maintaining a pro-tumorigenic, immunosuppressed microenvironment. We demonstrate housing glioma-bearing mice in enriched environment (EE) reverts the immunosuppressive phenotype of myeloid cells, by modulating inflammatory gene expression. Under these conditions, branching patrolling activity cells is increased, their phagocytic promoted....
Immune cells accumulating in the microenvironment of malignant tumors are tumor-educated, and contribute to its growth, progression evasion antitumor immune responses. Glioblastoma (GBM), common most primary brain tumor adults, shows considerable accumulation resident microglia peripheral macrophages, their polarization into tumor-supporting cells. There controversies regarding a functional phenotype glioma-associated microglia/macrophages (GAMs) due lack consistent markers. Previous...
Chromatin structure and accessibility, combinatorial binding of transcription factors to regulatory elements in genomic DNA control transcription. Genetic variations genes encoding histones, epigenetics-related enzymes or modifiers affect chromatin structure/dynamics result alterations gene expression contributing cancer development progression. Gliomas are brain tumors frequently associated with deregulation. We perform whole-genome mapping histone modifications, methylation patterns...
Chronic and acute myeloid leukemia evade immune system surveillance induce immunosuppression by expanding proleukemic Foxp3+ regulatory T cells (Tregs). High levels of immunosuppressive Tregs predict inferior response to chemotherapy, relapse, shorter survival. However, mechanisms that promote in leukemias remain largely unexplored. Here, we identify leukemic extracellular vesicles (EVs) as drivers effector Tregs. Using mouse model leukemia-like disease, found Rab27a-dependent secretion EVs...
Abstract Accumulating evidence suggests that glioma stem cells (GSCs), which are rare characterized by pluripotency and self-renewal ability, responsible for glioblastoma (GBM) propagation, recurrence resistance to therapies. Bone morphogenic proteins (BMPs) induce GSC differentiation, leads elimination of GSCs sensitization chemotherapeutics. Alterations in the epidermal growth factor receptor ( EGFR ) gene detected more than half GBMs; however, role chemoresistance remains unknown. Here,...
Local hypoxia occurs in most solid tumors and is associated with aggressive disease therapy resistance. Widespread changes gene expression play a critical role the biological response to hypoxia. However, research has focused on hypoxia‐inducible genes as opposed those that are decreased We demonstrate chromatin accessibility hypoxia, predominantly at promoters specific pathways impacted including DNA repair, splicing, R‐loop interactome. One of was DDX5 , encoding RNA helicase, DDX5, which...
Diffuse intrinsic pontine gliomas (DIPGs) are deadly pediatric brain tumors, non-resectable due to brainstem localization and diffusive growth. Over 80% of DIPGs harbor a mutation in histone 3 (H3.3 or H3.1) resulting lysine-to-methionine substitution (H3K27M). Patients with DIPG have dismal prognosis no effective therapy. We show that deacetylase (HDAC) inhibitors lead significant reduction the H3.3K27M protein (up 80%) multiple glioma cell lines. discover SB939-mediated loss is partially...
Abstract Glioblastoma (GBM) is the most common and lethal brain tumor in adults. Due to its fast proliferation, diffusive growth therapy resistance survival times are less than two years for patients with IDH-wildtype GBM. GBM noted considerable cellular heterogeneity, high stemness indices abundance of glioma stem-like cells known support progression, therapeutic recurrence. Doublesex- mab-3–related transcription factor a2 (DMRTA2) involved maintaining neural progenitor (NPC) cell cycle...
JAK (Janus kinase)/STAT (signal transducers and activators of transcription) signaling is involved in the regulation cell growth, differentiation apoptosis. Constitutive activation STATs, particular STAT3, observed a large number human tumors, including gliomas may contribute to oncogenesis by stimulating proliferation preventing apoptosis, thus it emerges as promising target for anti-cancer therapy. To investigate therapeutic potential blocking STAT3 glioma cells set small synthetic...
Abstract Despite surging interest in space travel recent decades, the impacts of prolonged, elevated exposure to galactic cosmic radiation (GCR) on human health remain poorly understood. This form ionizing causes significant changes biological systems including damage DNA structure by altering epigenetic phenotype with emphasis methylation. Building previous work Kennedy et al. (Sci Rep 8(1): 6709. 10.1038/S41598-018-24755-8), we evaluated spatial methylation patterns triggered high-LET ( 56...
Following CNS demyelination, oligodendrocyte progenitor cells (OPCs) are able to differentiate into either remyelinating oligodendrocytes (OLs) or Schwann (SCs). However, the signals that determine which type of cell is generated and underlying mechanisms involved have not been identified. Here, we show distinctive microenvironments created in discrete niches within demyelinated white matter fate decisions adult OPCs. By comparative transcriptome profiling demonstrate an ectopic,...