- Glycosylation and Glycoproteins Research
- Cancer-related Molecular Pathways
- Carbohydrate Chemistry and Synthesis
- Enzyme Production and Characterization
- Cancer, Hypoxia, and Metabolism
- Adipose Tissue and Metabolism
- RNA Research and Splicing
- Polysaccharides and Plant Cell Walls
- Diet and metabolism studies
- Pancreatic function and diabetes
- Microbial Metabolites in Food Biotechnology
- Diet, Metabolism, and Disease
- Cancer, Lipids, and Metabolism
- Genomics and Chromatin Dynamics
- RNA modifications and cancer
- Metabolism, Diabetes, and Cancer
- Galectins and Cancer Biology
- Toxin Mechanisms and Immunotoxins
- Epigenetics and DNA Methylation
- FOXO transcription factor regulation
- interferon and immune responses
- Botanical Research and Chemistry
- bioluminescence and chemiluminescence research
- Plant pathogens and resistance mechanisms
- Fungal Biology and Applications
Hebrew University of Jerusalem
2019-2024
National Institutes of Health
2015-2017
National Cancer Institute
2015-2017
Center for Cancer Research
2017
Weizmann Institute of Science
2008-2016
Tel Aviv University
2006-2010
Johns Hopkins University
2010
Edmond and Lily Safra Children's Hospital
2006
Sheba Medical Center
2006
University of Michigan
1968-1999
Primary hepatocytes are a vital tool in various biomedical research disciplines, serving as an ex vivo model for liver physiology. Obtaining high yields of viable primary mouse is technically challenging, limiting their use. Here, we present improved protocol based on the classic two-step collagenase perfusion technique. The washed by perfusion, dissociated collagenase, separated from other cells, and cultured. This was optimized to significantly reduce procedure duration improve hepatocyte...
Fasting elicits transcriptional programs in hepatocytes leading to glucose and ketone production. This program is regulated by many transcription factors (TFs). To understand how this complex network regulates the metabolic response fasting, we aimed at isolating enhancers TFs dictating it. Measuring chromatin accessibility revealed that fasting massively reorganizes liver chromatin, exposing numerous fasting-induced enhancers. By utilizing computational methods combination with dissecting...
Highlights•Only one-fifth of TF motifs show protection from DNA cleavage ("footprint")•Enzyme-specific cut bias profoundly and unavoidably affects footprint estimation•BaGFoot unbiasedly detects activity via TF-associated changes in accessibility•BaGFoot overcomes is amenable to both DNase-seq ATAC-seqSummaryIn response activating signals, transcription factors (TFs) bind regulate gene expression. binding can be measured by the bound sequence DNase digestion (i.e., footprint). Here, we...
This paper presents data on reactions of murine macrophages with a variety lectins, special focus Griffonia simplicifolia I-B4 isolectin, the only lectin we tried that distinguishes stimulated from resident populations. Specificity I reaction carbohydrate determinants at cell surface is shown by (i) ability alpha-galactosidase treatment intact cells to abolish all binding whereas beta-galactosidase has no effect binding, (ii) methyl alpha-D-galactopyranoside completely inhibit having (iii)...
Prostate cancer is the most common non-dermatologic malignancy in men Western world. Recently, a frequent chromosomal aberration fusing androgen regulated TMPRSS2 promoter and ERG gene (TMPRSS2/ERG) was discovered prostate cancer. Several studies demonstrated cooperation between TMPRSS2/ERG other defective pathways progression. However, unveiling of more specific which takes part, requires further investigation. Using immortalized epithelial cells we were able to show that over-expressing...
The carbohydrate moiety of carcinoembryonic antigen could be sequentially degraded by repeated cycles periodate oxidation, reduction, and mild acid hydrolysis (Smith degradation). After three complete degradations, all fucose sialic acid, 80% the galactose, 65% mannose, about 40% N-acetylglucosamine were eliminated without impairing ability to react with specific antisera against antigen. Inhibition studies in a antigen/rabbit anti-carcinoembryonic precipitating system oligosaccharides...
Uncontrolled accumulation of reactive oxygen species (ROS) causes oxidative stress and induces harmful effects. Both high ROS levels p53 mutations are frequent in human cancer. Mutant forms known to actively promote malignant growth. However, no mechanistic details about the contribution mutant excessive cancer cells. Herein we examined effect p53R273H, a commonly occurring mutated form, on expression phase 2 detoxifying enzymes, ability cells readopt reducing environment after exposure...
Abstract The cytokines interleukin 1β and 6 (IL-1β, IL-6) mediate the acute phase response (APR). In liver, they regulate secretion of proteins. Using RNA-seq in primary hepatocytes, we show that these transcription a bifurcated manner, leading to both synergistic antagonistic gene expression. By mapping changes enhancer landscape factor occupancy (using ChIP-seq), induction is achieved by assisted loading STAT3 on chromatin NF-κB. With IL-6 treatment alone, does not efficiently bind 20% its...
Fibroblasts located adjacent to the tumor [cancer-associated fibroblasts (CAFs)] that constitute a large proportion of cancer-associated stroma facilitate transformation process. In this study, we compared biological behavior CAFs were isolated from prostate their normal-associated fibroblast (NAF) counterparts. formed more colonies when seeded at low cell density, exhibited higher proliferation rate and less prone contact inhibition. contrast general notion high levels α-smooth muscle actin...
Abstract In this study, we focus on the analysis of a previously identified cancer-related gene signature (CGS) that underlies cross talk between p53 tumor suppressor and Ras oncogene. CGS consists large number known downstream target genes were synergistically upregulated by wild-type loss oncogenic H-RasG12V expression. Here show expression strongly correlates with malignancy. an attempt to elucidate molecular mechanisms underling cooperation H-RasG12V, distinguished pathways may account...
The p53 tumor suppressor protein is a transcription factor that initiates transcriptional programs aimed at inhibiting carcinogenesis. represses metabolic pathways support development (such as glycolysis and the pentose phosphate pathway (PPP)) enhances are considered counter-tumorigenic such fatty acid oxidation.In an attempt to comprehensively define regulated by p53, we performed two consecutive high-throughput analyses in human liver-derived cells with varying statuses. A gene expression...
Concomitant expression of mutant p53 and oncogenic Ras, leading to cellular transformation, is well documented. However, the mechanisms by which various categories cooperate with Ras remain largely obscure. In this study we suggest that different H-Ras in manners induce a unique pattern cancer related gene signature (CGS). The DNA-contact mutants (p53R248Q p53R273H) exhibited highest level CGS cooperating NFκB. Furthermore, Zn+2 region conformational (p53R175H p53H179R) induced elevating...