A5041416660- Cancer, Hypoxia, and Metabolism
- Mitochondrial Function and Pathology
- Physiological and biochemical adaptations
- Erythrocyte Function and Pathophysiology
- Erythropoietin and Anemia Treatment
- Telomeres, Telomerase, and Senescence
- Bioinformatics and Genomic Networks
- Genetics, Aging, and Longevity in Model Organisms
- T-cell and B-cell Immunology
- RNA modifications and cancer
- Molecular Biology Techniques and Applications
- Metabolomics and Mass Spectrometry Studies
- Plant-Microbe Interactions and Immunity
- Genomics and Phylogenetic Studies
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Cancer-related Molecular Pathways
- Chromosomal and Genetic Variations
- Liver Disease Diagnosis and Treatment
- Metabolism and Genetic Disorders
- Angiogenesis and VEGF in Cancer
- Neuroinflammation and Neurodegeneration Mechanisms
- Amino Acid Enzymes and Metabolism
- Biochemical Acid Research Studies
- Evolution and Paleontology Studies
- Single-cell and spatial transcriptomics
University of Haifa
2015-2025
Carmel (Israel)
2014-2025
Rebecca Sieff Hospital
2012
Yale University
2007
Abstract Background Subterranean blind mole rats (Spalax) are hypoxia tolerant (down to 3% O 2 ), long lived (>20 years) rodents showing no clear signs of aging or related disorders. In 50 years Spalax research, spontaneous tumors have never been recorded among thousands individuals . Here we addressed the questions (1) whether is resistant chemically-induced tumorigenesis, and (2) normal fibroblasts isolated from possess tumor-suppressive activity. Results Treating animals with...
Blind subterranean mole rats ( Spalax , Spalacidae) evolved adaptive strategies to cope with hypoxia that climaxes during winter floods in their burrows. By using real-time PCR, we compared gene expression of erythropoietin Epo ), a key regulator circulating erythrocytes, and hypoxia-inducible factor 1 α HIF-1 α), inducer, the kidneys white rats, Rattus norvegicus . Our results show significantly higher, quicker, longer responses different O 2 levels i ) In normoxia, both produce small...
ABSTRACT Dehydrin gene ( Dhn ) expression is associated with plant response to dehydration. The aim of the present study was investigate association differential genes 1, 3, 5, 6, and 9 drought tolerance found in wild barley Hordeum spontaneum ). Tolerant sensitive genotypes were identified from Israeli (Tabigha microsite) Jordanian (Jarash Waddi Hassa) populations (based on scoring water loss rate 390 genotypes). five up‐regulated by dehydration resistant genotypes. Notably, differences...
Reactive oxygen species (ROS)- and hypersensitive response (HR)-mediated cell death have long been known to play critical roles in plant immunity pathogens. Wheat powdery mildew caused by Blumeria graminis f. sp. tritici ( Bgt) is a destructive wheat pathogen. Here, we report quantitative analysis of the proportion infected cells with local apoplastic ROS (apoROS) versus intracellular (intraROS) accumulation various accessions that carry different disease resistance genes R genes) at series...
Highlights•Mouse pancreatic acinar and beta cells grow dramatically during postnatal life•Acinar cell growth is a major contributor to pancreas in mice•Postnatal of the human relies entirely on increased number•Acinar size inversely correlates with lifespan among 24 mammalian speciesSummaryDevelopmental processes different mammals are thought share fundamental cellular mechanisms. We report dramatic increase development rodents, accounting for much organ after birth. Hypertrophy involves...
Lacrimo-auriculo-dento-digital (LADD) syndrome is characterized by abnormalities in lacrimal and salivary glands, teeth, the distal limbs. Genetic studies have implicated heterozygous mutations fibroblast growth factor 10 (FGF10) FGF receptor 2 (FGFR2) LADD syndrome. However, it not clear whether (LADD mutations) are gain- or loss-of-function mutations. In order to reveal molecular mechanism underlying syndrome, we compared biological properties of FGF10 FGFR2 mutants activities their normal...
Abstract The blind subterranean mole rat Spalax shows a remarkable tolerance to hypoxia, cancer-resistance and longevity. Unravelling the genomic basis of these adaptations will be important for biomedical applications. RNA-Seq gene expression data were obtained from normoxic hypoxic liver tissue. Hypoxic broadly downregulates genes major function pathways. This energy-saving response is likely crucial adaptation low oxygen levels. In contrast, hypoxia-sensitive massive upregulation energy...
Telomere dynamics have been found to be better predictors of survival and mortality than chronological age. Telomeres, the caps that protect end linear chromosomes, are known shorten with age, inducing cell senescence aging. Furthermore, differences in age-related telomere attrition were established between short-lived long-lived organisms. However, whether length is a "biological thermometer" reflects biological state at certain point life or biomarker can influence conditions, delay...
In the subterranean rodent (Nanno)spalax galili, evolutionary adaptation to hypoxia is correlated with longevity and tumor resistance. Adapted gene-regulatory networks of Spalax might pinpoint strategies maintain health in humans. Comparing liver, kidney spleen transcriptome data from rat at normoxia, we identified differentially expressed gene pathways common multiple organs both species. Body-wide interspecies differences affected processes like cell death, antioxidant defense, DNA repair,...
The blind subterranean mole rat superspecies Spalax ehrenbergi has evolved adaptations that allow it to survive and carry out intensive activities in its highly hypoxic underground sealed burrows. A key component of this adaptation is a higher capillary density some tissues, primarily muscles used digging other energetic activities, resulting shorter diffusion distance for oxygen. Vascular endothelial growth factor (VEGF) an angiogenic critical angiogenesis during development found response...
The blind mole rat, Spalax, is the only mammalian species, to date, for which spontaneous cancer was never reported and resistance carcinogens- induced cancers demonstrated. However, underlying mechanisms are still poorly understood. fact that Spalax also a hypoxia-tolerant long-lived species implies molecular adaptations prevent genomic instability, underlies both aging. We previously demonstrated up-regulation of transcripts related DNA replication repair pathways in Spalax. Yet, no direct...
The subterranean blind mole rat, Spalax, experiences acute hypoxia-reoxygenation cycles in its natural habitat. At the cellular level, these conditions are known to promote genomic instability, which underlies both cancer and aging. However, Spalax is a long-lived animal resistant spontaneous induced cancers. To study this apparent paradox we utilized computational procedure that allows detecting differences transcript abundance between closely related above-ground Rattus norvegicus...
Blind subterranean mole rats of the Spalax ehrenbergi superspecies in Israel have evolved multiple adaptive strategies to face underground hypoxia. Hypoxia-inducible factor-1alpha (HIF-1alpha) and erythropoietin (Epo) are key factors development normal erythropoiesis angiogenesis. Here, we demonstrate via real-time polymerase chain reaction (PCR) quantification that fetal liver kidney express higher levels Epo mRNA than Rattus, generating reinforcement adapting it life an atmosphere abrupt...
Abstract The blind mole rat ( Spalax ) is a wild, long‐lived rodent that has evolved mechanisms to tolerate hypoxia and resist cancer. Previously, we demonstrated high DNA repair capacity low damage in fibroblasts following genotoxic stress compared with rats. Since the acquisition of senescence‐associated secretory phenotype (SASP) consequence persistent damage, investigated whether cellular senescence accompanied by an inflammatory response. undergo replicative (RS) etoposide‐induced...
Objective. The objective of the present study is to investigate effect rosiglitazone, metformin, ezetimibe, and valsartan (alone or in combinations) on paraoxonase (PON) activity PON-mRNA expression nonalcoholic fatty liver disease (NAFLD). Methods. 54 Male Sprague-Dawley rats were divided 9 groups: chow diet group (15 weeks); methionine-choline-deficient (MCDD) MCDD-treated groups for last 6 weeks with either metformin (M), rosiglitazone (R), plus (M+R), ezetimibe (E), (V), a combination...
Spalax, the blind mole rat, developed an extraordinary cancer resistance during 40 million years of evolution in a subterranean, hypoxic, thus DNA damaging, habitat. In 50 Spalax research, no spontaneous development has been observed. The mechanisms underlying this are still not clarified. We investigated genetic difference between and mice that might enable relative to development. compared responses treatment with carcinogen 3-Methylcholantrene, as model assess Spalax' cancer-resistance.We...
Different subtypes of macrophages have been shown to participate during the different stages in tissue repair. In late stage repair macrophages, following their engulfment apoptotic neutrophils, acquire a new phenotype termed alternatively-activated macrophages. These produce growth factors such as vascular endothelial factor (VEGF) that facilitate angiogenic response part restoration. As wound resolves capillary regression takes place. However, whether play role this is largely unknown....
Erythropoietin (Epo) is the primary regulator of erythropoiesis, controlling proliferation, maturation, and survival erythroid progenitor cells. The functions Epo are mediated through its specific receptor (EpoR) expressed mainly on surface cells, expression both responds to hypoxia. subterranean mole rat (Spalax) a unique model system study molecular mechanisms for adaptation Here, we cloned two forms Spalax EpoR: complete EpoR cDNA as well novel truncated bone marrow form. In full-length...
Erythropoietic functions of erythropoietin (EPO) are mediated by its receptor (EPO-R), which is present on the cell surface erythroid progenitors and induced hypoxia. We focused EPO-R from Spalax galili (sEPO-R), one four Israeli species subterranean blind mole rat, ehrenbergi superspecies, as a special natural animal model high tolerance to Led intriguing observation that most mouse (mEPO-R) retained in endoplasmic reticulum (ER), we hypothesized sEPO-R expressed at higher levels surface,...