A5021648941- melanin and skin pigmentation
- Advanced Radiotherapy Techniques
- MicroRNA in disease regulation
- Mast cells and histamine
- RNA regulation and disease
- Immunotherapy and Immune Responses
- Cancer-related molecular mechanisms research
- Sarcoma Diagnosis and Treatment
- RNA Research and Splicing
- Cardiomyopathy and Myosin Studies
- Biochemical Analysis and Sensing Techniques
- Neonatal Respiratory Health Research
- Cytokine Signaling Pathways and Interactions
- Skin Protection and Aging
- Genomics and Chromatin Dynamics
- Respiratory Support and Mechanisms
- Circular RNAs in diseases
- Neuroscience of respiration and sleep
- Melanoma and MAPK Pathways
- Cancer Cells and Metastasis
- Retinal Development and Disorders
- Circadian rhythm and melatonin
- RNA modifications and cancer
- interferon and immune responses
- Eating Disorders and Behaviors
Tel Aviv University
2016-2025
Tel Aviv Sourasky Medical Center
2025
Technion – Israel Institute of Technology
2002-2015
National Insurance Institute of Israel
2015
Massachusetts General Hospital
2010-2011
Harvard University
2006-2011
Dana-Farber Cancer Institute
2011
Harvard University Press
2008-2011
Vehicle Technologies Office
2009
Hebrew University of Jerusalem
2003-2005
Cancer-associated fibroblasts (CAFs) are highly prominent in breast tumors, but their functional heterogeneity and origin still largely unresolved. We report that bone marrow (BM)-derived mesenchymal stromal cells (MSCs) recruited to primary tumors lung metastases differentiate a distinct subpopulation of CAFs. show BM-derived CAFs functionally important for tumor growth enhance angiogenesis via up-regulation Clusterin. Using newly generated transgenic mice adoptive BM transplantations, we...
Ataxia–telangiectasia (A-T) is a pleiotropic genome instability syndrome resulting from the loss of homeostatic protein kinase ATM. The complex phenotype A-T includes progressive cerebellar degeneration, immunodeficiency, gonadal atrophy, interstitial lung disease, cancer predisposition, endocrine abnormalities, chromosomal instability, radiosensitivity, and segmental premature aging. Cultured skin fibroblasts patients exhibit senescence, highlighting association between cellular We found...
Transcriptional regulation requires the binding of transcription factors (TFs) to short sequence-specific DNA motifs, usually located at gene regulatory regions. Interestingly, based on a vast amount data accumulated from genomic assays, it has been shown that only small fraction all potential sites containing consensus motif given TF actually bind protein. Recent in vitro which exclude effects cellular environment, also demonstrate selective binding. An intriguing conjecture is surroundings...
Abstract MicroRNA (miRNA) biogenesis initiates co-transcriptionally, but how the Microprocessor machinery pinpoints locations of short precursor miRNA sequences within long flanking regions transcript is not known. Here we show that depends on DNA methylation. When coding sequence are highly methylated, miRNAs more expressed, have greater conservation, and likely to drive cancer-related phenotypes than encoded by unmethylated loci. We removal methylation from loci leads their downregulation....
During development, tissue-specific transcription factors regulate both protein-coding and non-coding genes to control differentiation. Recent studies have established a dual role for the factor Pax6 as an activator repressor of gene expression in eye, central nervous system, pancreas. However, molecular mechanism underlying inhibitory activity is not fully understood. Here, we reveal that Trpm3 intronic microRNA miR-204 are co-regulated by during eye development. probably best known...
During development, enhancers play pivotal roles in regulating gene expression programs; however, their involvement cancer progression has not been fully characterized. We performed an integrative analysis of DNA methylation, RNA-seq, and small RNA-seq profiles from thousands patients, including 25 diverse primary malignances seven body sites metastatic melanoma. found that are consistently the most differentially methylated regions (DMR) as progresses normal to tumors then metastases,...
Despite the remarkable successes of cancer immunotherapies, majority patients will experience only partial response followed by relapse resistant tumors. While treatment resistance has frequently been attributed to clonal selection and immunoediting, comparisons paired primary relapsed tumors in melanoma breast cancers indicate that they share clones. Here, we demonstrate both mouse models clinical human samples tumor cells evade immunotherapy generating unique transient cell-in-cell...
MITF and its related family members TFE3 TFEB heterodimerize with each other, recognize the same DNA sequences, are subject to many of post-translational modifications. We show that lysine residues within conserved small ubiquitin-like modifier (SUMO) consensus sites in these SUMO modification. Mutation significantly affects transcriptional activity but does not alter dimerization, binding, stability, or nuclear localization. Mutagenesis reducing number binding promoter TRPM1 from three one...
Microphthalmia-associated transcription factor (MITF) regulates normal melanocyte development and is also a lineage-selective oncogene implicated in melanoma clear-cell sarcoma (i.e., of soft parts). We have observed that MITF expression potently reduced under hypoxic conditions primary melanocytes clear cell cells through hypoxia inducible 1 (HIF1)-mediated induction the transcriptional repressor differentially expressed chondrocytes protein (DEC1) (BHLHE40), which subsequently binds...
Melanoma incidence continues to rise at an alarming rate while effective systemic therapies remain very limited. Microphthalmia-associated transcription factor (MITF) is required for development of melanocytes and amplified oncogene in a fraction human melanomas. also plays oncogenic role clear cell sarcomas, which typically exhibit melanoma-like features. Although pharmacologic suppression MITF potential interest variety clinical settings, it not known contain intrinsic catalytic activity...
Abstract Decoding heterogeneity of pluripotent stem cell (PSC)-derived neural progeny is fundamental for revealing the origin diverse progenitors, defining their lineages, and identifying fate determinants driving transition through distinct potencies. Here we have prospectively isolated consecutively appearing PSC-derived primary progenitors based on Notch activation state. We first isolate early neuroepithelial cells show broad Notch-dependent developmental proliferative potential....
<b><i>Background:</i></b> Several studies in animal models and human with obstructive sleep apnea syndrome (OSAS) demonstrated an increase cancer aggressiveness mortality. However, there is a need for further clinical evidence supporting correlation between OSAS incidence. <b><i>Objectives:</i></b> To reveal whether presence severity correlated incidence large homogenous patients’ cohort. <b><i>Methods:</i></b> We...
Abstract Sexual dimorphisms are responsible for profound metabolic differences in health and behavior. Whether males females react differently to environmental cues, such as solar ultraviolet (UV) exposure, is unknown. Here we show that exposure induces food-seeking behavior, food intake, behavior intake men, but not women, through epidemiological evidence of approximately 3,000 individuals throughout the year. In mice, UVB leads increased weight gain, with a sexual dimorphism towards males....
Cyclic AMP (cAMP) is a ubiquitous second messenger that regulates variety of biological processes. The magnitude and duration cAMP expression are regulated by both production hydrolysis. Melanocyte-stimulating hormone (MSH) plays crucial role in pigment cell differentiation via cAMP-regulated the master transcription factor MITF. We report identification phosphodiesterase 4D3 as direct target MSH/cAMP/MITF pathway. This creates negative feedback loop induces refractoriness to chronic...
The majority of mammalian microRNA (miRNA) genes reside within introns protein-encoding and non-coding genes, yet the mechanisms coordinating primary transcript processing into both mature miRNA spliced mRNA are poorly understood. Analysis melanoma invasion suppressor miR-211 expressed from intron 6 melastatin revealed that microprocessing promotes splicing exon 6–exon 7 junction by a mechanism requiring RNase III activity Drosha. Additionally, mutations in 5′ splice site (5′SS), but not...