A5015123620- Cancer-related molecular mechanisms research
- RNA modifications and cancer
- MicroRNA in disease regulation
- Cytokine Signaling Pathways and Interactions
- Glycosylation and Glycoproteins Research
- Liver Disease Diagnosis and Treatment
- Immune cells in cancer
- Genomics and Phylogenetic Studies
- Fibroblast Growth Factor Research
- RNA Research and Splicing
- Carbohydrate Chemistry and Synthesis
- NF-κB Signaling Pathways
- melanin and skin pigmentation
- Phagocytosis and Immune Regulation
- Galectins and Cancer Biology
- Circular RNAs in diseases
- Vibrio bacteria research studies
- Muscle Physiology and Disorders
- Inflammasome and immune disorders
- Fungal and yeast genetics research
- Immune Cell Function and Interaction
- Protein Kinase Regulation and GTPase Signaling
- Proteoglycans and glycosaminoglycans research
- Cytomegalovirus and herpesvirus research
- Gut microbiota and health
Hadassah Medical Center
2016-2024
Hebrew University of Jerusalem
2005-2024
Israeli Centers for Research Excellence
2015-2024
Core Laboratories (United States)
2022
Technion – Israel Institute of Technology
2013-2017
Hadassah Academic College
2017
Ludwig-Maximilians-Universität München
2006
Freie Universität Berlin
2006
Charité - Universitätsmedizin Berlin
2006
University of Manchester
2005
Abstract Several long noncoding RNAs (lncRNA) are abrogated in cancer but their precise contributions to oncogenesis still emerging. Here we report that the lncRNA MALAT1 is upregulated hepatocellular carcinoma and acts as a proto-oncogene through Wnt pathway activation induction of oncogenic splicing factor SRSF1. Induction SRSF1 by modulates targets, enhancing production antiapoptotic isoforms activating mTOR modulating alternative S6K1. Inhibition expression or activity abolishes...
Abstract Acinar metaplasia is an initial step in a series of events that can lead to pancreatic cancer. Here we perform single-cell RNA-sequencing mouse pancreas during the progression from preinvasive stages tumor formation. Using reporter gene, identify metaplastic cells originated acinar and express two transcription factors, Onecut2 Foxq1. Further analyses cell heterogeneity define six types states, including stomach-specific types. Localization mixture different same pre-malignant...
The circadian clock of the honey bee is implicated in ecologically relevant complex behaviors. These include time sensing, time-compensated sun-compass navigation, and social behaviors such as coordination activity, dance language communication, division labor. molecular underpinnings are largely unknown. We show that gene structure expression pattern more similar to mouse than Drosophila. genome does not encode an ortholog Drosophila Timeless ( Tim1 ), has only mammalian type Cryptochrome...
Zika virus (ZIKV) has emerged as a cause of congenital brain anomalies and range placenta-related abnormalities, highlighting the need to unveil modes maternal-fetal transmission. The most likely route vertical ZIKV transmission is via placenta. earliest events in maternal decidua, representing uterine aspect chimeric placenta, have remained unexplored. Here, we show that replicates first-trimester human maternal-decidual tissues grown ex vivo three-dimensional (3D) organ cultures. An...
The nasal mucosa constitutes the primary entry site for respiratory viruses, including severe acute syndrome coronavirus 2 (SARS-CoV-2). While imbalanced innate immune response of end-stage disease 2019 (COVID-19) has been extensively studied, earliest stages SARS-CoV-2 infection at mucosal have remained unexplored. Here, we employed and influenza virus in native multi-cell-type human turbinate lung tissues
Objective Cellular senescence limits tumourigenesis by blocking the proliferation of premalignant cells. Additionally, however, senescent cells can exert paracrine effects influencing tumour growth. Senescent are present in pancreatic intraepithelial neoplasia (PanIN) lesions, yet their on disease poorly characterised. It is currently unknown whether senolytic drugs, aimed at eliminating from could be beneficial development. Design To uncover functions and potential contribution to early...
The molecular program underlying infrequent replication of pancreatic β-cells remains largely inaccessible. Using transgenic mice expressing green fluorescent protein in cycling cells, we sorted live, replicating and determined their transcriptome. Replicating upregulate hundreds proliferation-related genes, along with many novel putative cell cycle components. Strikingly, genes involved β-cell functions, namely, glucose sensing insulin secretion, were repressed. Further studies using...
Heparanase is an endo-beta-D-glucuronidase that degrades heparan sulfate in the extracellular matrix and cell surfaces. Human proheparanase produced as a latent 65-kDa polypeptide undergoing processing at two potential proteolytic cleavage sites, located Glu109-Ser110 (site 1) Gln157-Lys158 2). Cleavage of yields 8- 50-kDa subunits heterodimerize to form active enzyme. The fate linker segment (Ser110-Gln157) residing between subunits, mode processing, protease(s) engaged are currently...
Skin sun exposure induces two protection programs: stress responses and pigmentation, the former within minutes latter only hours afterward. Although serving same physiological purpose, it is not known whether how these programs are coordinated. Here, we report that UVB every other day significantly more skin pigmentation than higher frequency of daily exposure, without an associated increase in responses. Using mathematical modeling empirical studies, show melanocyte master regulator, MITF,...
Objective Failing to properly repair damaged DNA drives the ageing process. Furthermore, age-related inflammation contributes manifestation of ageing. Recently, we demonstrated that efficiency diethylnitrosamine (DEN)-induced double-strand breaks (DSBs) rapidly declines with age. We therefore hypothesised age, decline in damage stems from inflammation. Design used DEN-induced mouse livers and compared their resolution different ages following various permutations aimed at manipulating liver...
Article4 July 2022Open Access Transparent process Single-cell transcriptomics reveals a senescence-associated IL-6/CCR6 axis driving radiodermatitis Mor Paldor orcid.org/0000-0001-7210-1351 The Goldyne-Savad Institute of Gene Therapy, Hadassah Hebrew University Hospital, Jerusalem, Israel Contribution: Conceptualization, Investigation, Writing - original draft Search for more papers by this author Orr Levkovitch-Siany orcid.org/0000-0002-3798-2576 Methodology Dana Eidelshtein Investigation...
Abstract Extracellular vesicles (EVs) are important mediators of communication between cells. Here, we reveal a new mode intercellular by melanosomes, large EVs secreted melanocytes for melanin transport. Unlike small EVs, which disintegrated within the receiver cell, melanosomes stay intact them, gain unique protein signature, and can then be further transferred to another cell as “second-hand” EVs. We show that melanoma-secreted passaged through epidermal keratinocytes or dermal...
The N-terminal domain (NTD) of α-amino-3-hydroxy-5-methylisoxazolepropionate (AMPA) and kainate glutamate receptors plays an important role in controlling subtype specific receptor assembly. To identify NTD subdomains involved this process we generated AMPA 3 (GluR3) mutants having intra-NTD substitutions with the corresponding regions GluR6 tested their ability to form functional heteromers wild-type subunits. chimeric design was based on homology metabotropic GluR1, shown two globular...
Hereditary inclusion body myopathy (HIBM), a neuromuscular disorder, is caused by mutations in UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase (GNE), the key enzyme of sialic acid biosynthesis. To date, more than 40 different GNE gene have been reported to cause disease. Ten them, representing both functional domains GNE, were recombinantly expressed insect cells (Sf9). Each mutants that was analyzed displayed reduction two known activities, thus revealing may also influence...
Porphyromonas gingivalis is a Gram-negative anaerobic bacterium strongly associated with periodontal disease. Toll-like receptor 2 (TLR2) indispensable for the host response to P. gingivalis, but escapes from immune clearance via TLR2-dependent activation of phosphoinositide-3-kinase (PI3K). To probe escape pathway we analyzed TLR2 interactome induced following infection or by synthetic lipopeptide TLR2/1 agonist on human macrophages overexpressing TLR2. Interacting proteins were stabilized...
Abstract Senescent cells can influence the function of tissues in which they reside, and their propensity for disease. A portion adult human pancreatic beta express senescence marker p16, yet it is unclear whether are a senescent state, how this affects insulin secretion. We analyzed single-cell transcriptome datasets cells, found that p16-positive gene signatures, as well elevated levels beta-cell maturation genes, consistent with enhanced functionality. beta-like culture undergo chromatin...
Abstract Gliovirin is a strong anti‐oomycete and candidate anticancer compound. It produced by “P” strains of the plant disease biocontrol fungus Trichoderma virens involved in biological control certain pathogens. Even though compound known for more than three decades, neither genes nor biosynthetic pathway are known. We have sequenced whole genome gliovirin producing strain T. discovered novel gene cluster comprising 22 genes. Disruption non‐ribosomal peptide synthetase eliminated...
BACKGROUNDCytomegalovirus (CMV) is the most common intrauterine infection, leading to infant brain damage. Prognostic assessment of CMV-infected fetuses has remained an ongoing challenge in prenatal care, absence established biomarkers congenital CMV (cCMV) infection severity. We aimed identify prognostic cCMV-related fetal injury.METHODSWe performed global proteome analysis mid-gestation amniotic fluid samples, comparing with severe cCMV that asymptomatic fetuses. The levels selected...
NKp46 is a member of group receptors collectively termed natural cytotoxicity (NCRs) that are expressed by killer (NK) cells. NCRs capable mediating direct killing tumor and virus-infected cells NK We have recently shown recognizes the heparan sulfate moieties membranal proteoglycans (HSPGs), thus enabling lysis In current study, we further examined residues in may be involved binding on On basis both electrostatic potential map comparison to heparin site human fibronectin, predicted...
Hepatocellular carcinoma (HCC) typically develops on a background of chronic hepatitis for which the proinflammatory cytokine IL6 is conventionally considered crucial driving factor. Paradoxically, also acts as hepatoprotective factor in liver injury. Here we used multidrug-resistant gene 2 knockout (Mdr2-/-) mouse model to elucidate potential roles hepatitis-associated cancer. Long-term analysis three separate IL6/Stat3 signaling-deficient Mdr2-/- strains revealed aggravated injury with...