A5057859390- Liver Disease Diagnosis and Treatment
- Proteoglycans and glycosaminoglycans research
- Fibroblast Growth Factor Research
- RNA regulation and disease
- Cancer, Hypoxia, and Metabolism
- RNA Research and Splicing
- Cancer-related Molecular Pathways
- CRISPR and Genetic Engineering
- Glycosylation and Glycoproteins Research
- Cell Adhesion Molecules Research
- Angiogenesis and VEGF in Cancer
- Liver physiology and pathology
- bioluminescence and chemiluminescence research
- Peptidase Inhibition and Analysis
- Hepatitis B Virus Studies
- Organ Transplantation Techniques and Outcomes
- Ubiquitin and proteasome pathways
- High Altitude and Hypoxia
- Liver Disease and Transplantation
- Liver Diseases and Immunity
- Radiomics and Machine Learning in Medical Imaging
- Platelet Disorders and Treatments
- Economic and Financial Impacts of Cancer
- Viral Infectious Diseases and Gene Expression in Insects
- Bariatric Surgery and Outcomes
Sheba Medical Center
2009-2022
California Liver Research Institute
2013-2015
Tel Aviv University
2007-2012
Edmond and Lily Safra Children's Hospital
2007
Weizmann Institute of Science
1993-2006
Brigham and Women's Hospital
2003-2006
Dana-Farber Brigham Cancer Center
2003-2006
Harvard University
2003-2006
Dana-Farber Cancer Institute
2003-2006
Howard Hughes Medical Institute
2003-2005
Adenosine-to-inosine (A-to-I) RNA editing was recently shown to be abundant in the human transcriptome, affecting thousands of genes. Employing a bioinformatic approach, we identified significant global hypoediting Alu repetitive elements brain, prostate, lung, kidney, and testis tumors. Experimental validation confirmed this finding, showing significantly reduced sequences within MED13 transcripts brain tissues. Looking at specific recoding noncoding sites, including cancer-related genes,...
Many human diseases are characterized by the development of tissue hypoxia. Inadequate oxygenation can cause cellular dysfunction and death. Tissues use many strategies, including induction angiogenesis alterations in metabolism, to survive under hypoxic conditions. The heterodimeric transcription factor hypoxia-inducible (HIF) is a master regulator genes that promote adaptation HIF activity linked oxygen availability because members EGLN family hydroxylate HIFα subunits on specific prolyl...
Hypoxia refers to below-normal levels of oxygen in air, blood, or tissue.Tissue hypoxia leads cellular dysfunction and ultimately can lead cell death.Causes tissue include (a) decreased blood oxygenation (such as occurs certain pulmonary disorders), (b) altered release from hemoglobin (associated with some hemoglobinopathies), (c) impaired delivery leading localized anemia (i.e., ischemia) a result low cardiac output vascular obstruction.In order adapt hypoxia, mammals use number...
Heparan sulfate proteoglycans (HSPG) are obligatory for receptor binding and mitogenic activity of basic fibroblast growth factor (bFGF). The capacity various species heparin heparan (HS) to promote bFGF was investigated using both Chinese hamster ovary mutant cells deficient in cell surface HSPG a soluble receptor-alkaline phosphatase fusion protein. Highly sulfated oligosaccharides were more effective than medium low fractions the same size oligosaccharide. O-Sulfation found be critical...
Leukocyte and platelet integrins rapidly alter their affinity adhesiveness in response to various activation (inside-out) signals. A rare leukocyte adhesion deficiency (LAD), LAD-III, is associated with severe defects integrin activation. We report two new LAD cases which lymphocytes, neutrophils, platelets share β1, β2, β3 Patients were both homozygous for a splice junction mutation CalDAG-GEFI gene, key Rap-1/2 guanine exchange factor (GEF). Both mRNA protein levels of the GEF diminished...
Alternative mRNA splicing is a major mechanism for gene regulation and transcriptome diversity. Despite the extent of phenomenon, specificity machinery are only partially understood. Adenosine-to-inosine (A-to-I) RNA editing pre-mRNA by ADAR enzymes has been linked to in several cases. Here we used bioinformatics approaches, RNA-seq exon-specific microarray knockdown cells globally examine how its A-to-I activity influence alternative splicing. Although rarely targets canonical acceptor,...
Conditional alleles containing LoxP recombination sites, in conjunction with Cre recombinase delivered by a variety of means, allows for spatial and temporal control gene expression mouse models. Here we describe strain which luciferase (Luc) cDNA, preceded LoxP-stop-LoxP (L-S-L) cassette, was introduced into the ubiquitously expressed ROSA26 locus. Mouse embryo fibroblasts derived from this after Cre-mediated vitro. L-S-L-Luc/+ mice diffuse or liver-restricted pattern, as determined...
Background Hypoxia inducible factor-1α (HIF-1α) is responsible for the majority of HIF-1-induced gene expression changes under hypoxia and "angiogenic switch" during tumor progression. HIF-1α often upregulated in tumors leading to more aggressive growth chemoresistance, therefore representing an important target antitumor intervention. We previously reported that zinc downregulated levels. Here, we evaluated molecular mechanisms zinc-induced downregulation whether affected also vivo....
During liver injury, hepatic stellate cells (HSCs) can undergo activation and transform into alpha-smooth muscle actin (αSMA)-expressing contractile myofibroblast-like cells, leading to deposition of excessive scar matrix. We have recently demonstrated that depletion adenosine deaminase acting on double-stranded RNA (ADAR1) from mouse hepatocytes leads HSC induction inflammation fibrosis is mediated by interleukin 6 (IL-6). Our aim was identify characterize the molecular pathways involved in...
Hepatocellular carcinoma (HCC) is the second leading cause of cancer-related mortality worldwide. While cirrhosis main risk factor for HCC, factors influencing progression from to HCC remain largely unknown. Gut microbiota plays a key role in liver diseases; however, its association with remains elusive. This study aimed elucidate microbial differences between patients HCC-associated (HCC-cirrhosis) and cirrhotic without healthy volunteers explore associations diet, lifestyle, microbiome...
Control of proliferation and differentiation by the retinoblastoma tumor suppressor protein (pRB) related family members depends upon their interactions with key cellular substrates. Efforts to identify such targets led isolation a novel protein, EID-1 (for E1A-like inhibitor 1). Here, we show that is potent link this activity its ability inhibit p300 (and highly molecule, CREB-binding or CBP) histone acetylation activity. rapidly degraded proteasome as cells exit cell cycle. Ubiquitination...
Basic fibroblast growth factor (bFGF) is known to bind its cell-surface receptors with high affinity and in a heparin-dependent manner. In an attempt predict the receptor recognition site on bFGF we screened phage-epitope libraries monoclonal antibodies DG2 DE6, which inhibit binding receptor. On affinity-isolated phages, identified several peptide sequences as putative antibody-binding epitopes bFGF. The library shared consensus sequence Pro-(Pro/Ser)-Gly-His-(Tyr/Phe)-Lys, corresponding...
Adenosine to Inosine (A-to-I) RNA editing is a site-specific modification of transcripts, catalyzed by members the ADAR (Adenosine Deaminase Acting on RNA) protein family. occurs in human thousands different sites. Some sites are located protein-coding regions but majority found non-coding regions, such as 3′UTRs, 5′UTRs and introns - mainly Alu elements. While all tissues, highest levels brain. It was shown that within increased during embryogenesis after birth crucial for organism...
Interaction of basic fibroblast growth factor (FGF-2) with heparin or heparan sulfate proteoglycans (HSPGs) is required for receptor activation and initiation biological responses. To gain insight into the mechanism FGF by FGF-2 heparin, we have used NMR, dynamic light scattering, HSPG-deficient cells cell-free systems. The first 28 N-terminal residues in were found to be highly mobile flexible, consistent disorder both NMR X-ray structures. structure an FGF-2−heparin−decasaccharide complex...
Post-transcriptional events play an important role in human development. The question arises as to whether Adenosine Inosine RNA editing, catalyzed by the ADAR (Adenosine Deaminase acting on RNA) enzymes, differs embryogenesis and adulthood. We tested editing of various target genes coding (FLNA, BLCAP, CYFIP2) non-coding sequences at their Alu elements (BRCA1, CARD11, RBBP9, MDM4, FNACC), well transcriptional levels ADAR1 enzymes. This analysis was performed five fetal adult tissues: brain,...
Fulminant hepatitis failure (FHF) is marked by the sudden loss of hepatic function, with a severe life-threatening course in persons no prior history liver disease. Interleukin (IL)-1α and IL-1β are key inflammatory cytokines but little known about their role development FHF. The aim this study was to assess involvement IL-1α progression LPS/GalN-induced FHF.WT, or deficient mice were injected LPS/GalN. Blood tissue collected at different time points, FHF related pathways examined.After...
Adenosine deaminase acting on RNA (ADAR) 1 binds and edits double-stranded (ds) secondary structures found mainly within untranslated regions of many transcripts. In the current research, our aim was to study role ADAR1 in liver homeostasis. As previous studies show a conserved immunoregulatory function for mammalians, we focused its preventing chronic hepatic inflammation associated activation stellate cells produce extracellular matrix promote fibrosis. We that hepatocytes specific knock...
ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTDiminished Heparin Binding of a Basic Fibroblast Growth Factor Mutant Is Associated with Reduced Receptor Binding, Mitogenesis, Plasminogen Activator Induction, and in vitro AngiogenesisLu-Yuan Li, Michal Safran, David Aviezer, Peter Boehlen, Andrew P. Seddon, Avner YayonCite this: Biochemistry 1994, 33, 36, 10999–11007Publication Date (Print):September 13, 1994Publication History Published online1 May 2002Published inissue 13 September...