A5048404435- Acute Myeloid Leukemia Research
- Immunotherapy and Immune Responses
- T-cell and B-cell Immunology
- Immune Cell Function and Interaction
- Cancer Genomics and Diagnostics
- Hematopoietic Stem Cell Transplantation
- Multiple Sclerosis Research Studies
- Neuroinflammation and Neurodegeneration Mechanisms
- Cannabis and Cannabinoid Research
- Acute Lymphoblastic Leukemia research
- Cell Adhesion Molecules Research
- Systemic Lupus Erythematosus Research
- Protein Degradation and Inhibitors
- Epigenetics and DNA Methylation
- Retinal Development and Disorders
- Neurogenesis and neuroplasticity mechanisms
- Immune cells in cancer
- Nuclear Structure and Function
- DNA Repair Mechanisms
- Myeloproliferative Neoplasms: Diagnosis and Treatment
- Analytical Chemistry and Sensors
- Advanced biosensing and bioanalysis techniques
- vaccines and immunoinformatics approaches
- Immune Response and Inflammation
- RNA Research and Splicing
Weizmann Institute of Science
2016-2025
University Hospital Heidelberg
2019
Heidelberg University
2019
European Molecular Biology Laboratory
2019
Israel Institute for Biological Research
1997-2001
Technion – Israel Institute of Technology
1998
BACKGROUND AND PURPOSE Cannabis extracts and several cannabinoids have been shown to exert broad anti‐inflammatory activities in experimental models of inflammatory CNS degenerative diseases. Clinical use many is limited by their psychotropic effects. However, phytocannabinoids like cannabidiol (CBD), devoid psychoactive activity, are, potentially, safe effective alternatives for alleviating neuroinflammation neurodegeneration. EXPERIMENTAL APPROACH We used autoimmune encephalomyelitis (EAE)...
Abstract Both fatty bone marrow (FBM) and somatic mutations in hematopoietic stem cells (HSCs), also termed clonal hematopoiesis (CH) accumulate with human aging. However it remains unclear whether FBM can modify the evolution of CH. To address this question, we herein present interaction between CH two preclinical male mouse models: after sub-lethal irradiation or castration. An adipogenesis inhibitor (PPARγ inhibitor) is used both models as a control. A significant increase self-renewal be...
Abstract Chemokines and chemokine receptors establish a complex network modulating immune cell migration localization. These molecules were also suggested to mediate the differentiation of leukocytes; however, their intrinsic, direct regulation lymphocyte fate remained unclear. CCR2 is main receptor inducing macrophage monocyte recruitment sites inflammation, it expressed on T cells. To assess whether directly regulates responses, we followed fates CCR2−/− cells in cell–specific inflammatory...
Our previous studies showed that the non-psychoactive cannabinoid, cannabidiol (CBD), ameliorates clinical symptoms in mouse myelin oligodendrocyte glycoprotein (MOG)35-55-induced experimental autoimmune encephalomyelitis model of multiple sclerosis (MS) as well decreases memory MOG35-55-specific T cell (TMOG) proliferation and cytokine secretion including IL-17, a key factor. The mechanisms these activities are currently poorly understood.Herein, using microarray-based gene expression...
Cannabidiol (CBD), the main non-psychoactive cannabinoid, has been previously shown by us to ameliorate clinical symptoms and decrease inflammation in myelin oligodendrocyte glycoprotein (MOG)35-55-induced mouse experimental autoimmune encephalomyelitis model of multiple sclerosis as well MOG35-55-induced T cell proliferation IL-17 secretion. However, mechanisms CBD anti-inflammatory activities are unclear.Here we analyzed effects on splenocytes (source accessory cells antigen presenting...
Donor clonal hematopoiesis may be transferred to the recipient through allogeneic hematopoietic stem cell transplantation (HSCT), but potential for adverse long-term impact on transplant outcomes remains unknown. A total of 744 samples from 372 recipients who received HSCT and corresponding donors were included. Bar-coded error-corrected sequencing using a modified molecular inversion probe capture protocol was performed, which targeted 33 genes covering mutations involved in with...
Demyelination and axonal degeneration, hallmarks of multiple sclerosis (MS), are associated with the central nervous system (CNS) inflammation facilitated by C-X-C motif chemokine 12 (CXCL12) chemokine. Both in MS experimental autoimmune encephalomyelitis (EAE), deleterious CNS has been upregulation CXCL12 expression CNS. We investigated dynamics progression clinical EAE following spontaneous recovery, a focus on hippocampal neurogenic dentate gyrus (DG) corpus callosum (CC) spontaneously...
Abstract Background Multiple sclerosis (MS) is associated with pathogenic autoimmunity primarily focused on major CNS-myelin target antigens including myelin basic protein (MBP), proteolipidprotein (PLP), oligodendrocyte (MOG). MS a complex trait whereby the HLA genes, particularly class-II genes of HLA-DR15 haplotype, dominate genetic contribution to disease-risk. Due strong linkage disequilibrium in HLA-II region, it has been hard establish precisely whether functionally relevant effect...
Dimethylheptyl-cannabidiol (DMH-CBD), a non-psychoactive, synthetic derivative of the phytocannabinoid cannabidiol (CBD), has been reported to be anti-inflammatory in RAW macrophages. Here, we evaluated effects DMH-CBD at transcriptional level BV-2 microglial cells as well on proliferation encephalitogenic T cells.BV-2 were pretreated with DMH-CBD, followed by stimulation endotoxin lipopolysaccharide (LPS). The expression levels selected genes involved stress regulation and inflammation...
An antagonistic center-surround receptive field is a key feature in sensory processing, but how it contributes to specific computations such as direction selectivity often unknown. Retinal On-starburst amacrine cells (SACs), which mediate direction-selective ganglion (DSGCs), exhibit organization: depolarizing light increments and decrements their center surround, respectively. We find that repetitive stimulation exhausts SAC enhances its surround use study responses contribute selectivity....
Abstract The mutational mechanisms underlying recurrent deletions in clonal hematopoiesis are not entirely clear. In the current study we inspect genomic regions around myeloid malignancies, and identify microhomology-based signatures CALR , ASXL1 SRSF2 loci. We demonstrate that these result of double stand break repair by a PARP1 dependent microhomology-mediated end joining (MMEJ) pathway. Importantly, provide evidence originate pre-leukemic stem cells. While DNA polymerase theta (POLQ) is...
Cannabidiol (CBD), the non-psychoactive cannabinoid, has been previously shown by us to decrease peripheral inflammation and neuroinflammation in mouse experimental autoimmune encephalomyelitis (EAE) model of multiple sclerosis (MS). Here we have studied anti-inflammatory effects newly synthesized derivatives natural (-)-CBD ((-)-8,9-dihydro-7-hydroxy-CBD; HU-446) synthetic (+)-CBD ((+)-8,9-dihydro-7-hydroxy-CBD; HU-465) on activated myelin oligodendrocyte glycoprotein (MOG)35-55-specific...
Abstract Myelin oligodendrocyte glycoprotein (MOG) is an important myelin target antigen, and MOG‐induced EAE now a widely used model for multiple sclerosis. Clonal dissection revealed that in H‐2 b mice associated with activation of unexpectedly large number T cell clones reactive against the encephalitogenic epitope MOG35–55. These expressed extremely diverse TCR no obvious CDR3α/CDR3β motif(s). Despite extensive diversity, cells required MOG40–48 as their common core shared MOG44F major...
Abstract Microglia are established in embryogenesis forming a self-containing cellular compartment resisting seeding with cells derived from adult definitive hematopoiesis. We report that monocyte-derived macrophages (MoMΦ) accumulate the brain of aging mice distinct topology, including nigrostriatum and medulla, but not frontal cortex. Parenchymal MoMΦ adopt bona fide microglia expression profiles. Unlike microglia, these (MoMg) due to their hematopoietic origin targets clonal hematopoiesis...
Antigen-induced peripheral tolerance is potentially one of the most efficient and specific therapeutic approaches for autoimmune diseases. Although highly effective in animal models, antigen-based strategies have not yet been translated into practicable human therapy, several clinical trials using a single antigen or peptidic-epitope multiple sclerosis (MS) yielded disappointing results. In these trials, however, apparent complexity dynamics pathogenic autoimmunity associated with MS, which...
The absorption and desorption of chlorobenzene, o-dichlorobenzene, chloroform in poly[n-butyl methacrylate] (PBMA) was studied polymer-coated 104 MHz surface acoustic wave (SAW) sensors, free-standing polymer films by thermogravimetric analysis (TGA). sorption processes were analyzed a Fickian simulation best-fit partition, diffusion coefficients derived. Good correlations found between simulated observed data. Partition derived from SAW response independent coating thickness to be about two...
Abstract The encephalitogenic potential of oligodendrocyte-specific protein (OSP) in mice, its specific localization the intralamellar tight junctions CNS myelin, and detection autoreactivity against OSP multiple sclerosis (MS) strongly suggest relevance pathogenesis MS. In this study, we have characterized autoimmune T B cells that are associated with clinicopathological manifestations OSP-induced MS-like disease mice by using recombinant soluble mouse (smOSP) synthetic overlapping peptides...