2024 research activities
Overview
The molecular mechanisms underlying cell structures, dynamics and fate, and their involvement in embryonic development and cancer are among the primary topics of interest of the Department. These include studies on the mode of action of growth factors and the nature of signals triggered by them in target cells following binding to specific surface receptors. Growth regulation is also approached through the study of suppressor genes encoding such proteins as p53, which inhibit proliferation and drive cells towards differentiation or apoptosis. These studies, focusing on the mechanisms stimulate cell proliferation, differentiation, or death, can elucidate the basis for cancerous transformation in a large variety of systems. Overproduction or hyperactivation of growth-promoting systems was shown to have an oncogenic (cancer-causing) effect, and a similar process may be induced when growth-suppressor or apoptosis-inducing genes fail to function. The levels at which cell structure, activity and fate are studied in this department and the focus of these studies are many and diverse, including the characterization of soluble growth factors and their receptors, the nature of complex signal transduction pathways, the action of specific regulators of cytokine action, rearrangement of genes associated with oncogenic processes, and the properties of tumor suppressor and apoptosis promoting genes. Since such processes involve networks of interacting factors, we are also interested in mathematical modeling and computerized analysis of biological gene circuits.
In addition, there is broad interest in the molecular mechanisms of cell adhesion and their involvement in the regulation of cell fate. These studies include characterization of the basic rules underlying adhesive interactions, the binding of surface-associated adhesion molecules with the cytoskeleton, and the nature of growth- and differentiation-promoting signals triggered by adhesive interactions. Of special interest are proteins such as β-catenin, which play a crucial role in reinforcing cell-cell adhesions as well as triggering gene expression.
ScientistsShow details
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Prof. Uri Alon
Combining theoretical and experimental methods to discover design principles of biological circuitsSystems level analysis of gene regulation networks, with E. coli as a model system.Systems ImmunologyCollaboration with: Nir FriedmanEvolution
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Prof. Avri Ben-Ze'ev
Epithelial-mesenchymal transition (EMT), cancer stem cells (CSCs) and Wnt target genes in colon cancer metastasisMechanisms regulating L1CAM-mediated colon cancer invasion and metastasisThe interplay between the role of beta-catenin in cell adhesion and signaling during colon cancer development.The molecular basis and signaling roles of nerve cell adhesion receptors in colon cancer metastasisThe role of novel beta-catenin target genes in tumor development and metastasis
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Prof. Alexander D. Bershadsky
Integrin-mediated cell-matrix adhesions as mechanosensors: molecular requirements for the force-induced focal adhesion growth.Cell-cell contact-dependent regulation of the actin cytoskeleton and microtubule system: Role of p120 catenin and other components of cadherin adhesion complex.Role of myosin-driven contractility in the retrograde surface flow and cell motility.Cooperation between neuregulin, ErbB-family receptors, and cell surface heparan sulfate proteoglycans in the regulation of cell motility and morphogenesis.
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Prof. Eli Canaani
Comparison of the properties of the leukemogenic ALL-1 fusion proteins with those of normal ALL-1.Transcription profiles of primary tumors with ALL-1 rearrangements.Functions of the human ASH1 protein.Studies of the ALR gene.
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Prof. Benjamin Geiger
Molecular diversity of adhesion complexesThe roles of mechanical force in adhesion developmentRole of phosphorylation in regulating cell adhesion and migrationSignaling from the ECMCell adhesion and migration in cancerQuantitatibve automated microscopy and high throughput screens
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Dr. Shalev Itzkovitz
Design Principles of mammalian tissuesSpatially resolved single cell genomicsmRNA localization in tissues
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Professor Emeritus Zvi Kam
Cellular BiophysicsCollaboration with: Benjamin Geiger, John Sedat, David Agard (UCSF)Quantitative analysis of structural features and dynamic changes in cells using microscope imagingHigh throughput high-definition microscopy application in systems cell biologyAdaptive optics methods applied to thick sample imagingCell level informatics
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Prof. Valery Krizhanovsky
The role of cellular senescence in aging and age-related diseasesCollaboration with: Uri AlonThe dynamics of senescent cells during agingThe role of senescent cells in lung fibrosis and chronic obstructive pulmonary diseaseThe role of senescent cells in Alzheimer's diseaseAnalysis of senescent cells heterogeneity on transcriptomic, proteomic and metabolomic levelsMechanisms of interaction of senescent cells with their microenvironmentInteraction of senescent cells with the immune systemCellular senescence in cancer development and treatmentCollaboration with: Ittai Ben-Porath, Hebrew UniversitySenescent cells in pre-malignant lesionsTherapy-induced senescence in cancerSenescence during embryonic developmentCollaboration with: Dr. Tal Biron-Shental, Meir HospitalSenescence in syncytiotrophoblast is disrupted during intra-uteral growth restriction (IUGR)
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Prof. Sima Lev
Signaling networks in cancer development and metastasisCollaboration with: Thomas Karn, Eytan Ruppin, Gordon Mills, Flavio Maina, Frank Westermann, Yosef YardenTumorigenic signaling networks in triple negative breast cancer (TNBC) subtypesCombination therapy, drug resistance, and cancer stem cellsFerroptosis and TNBC therapyReceptor Tyrosine Kinases (RTKs) (AXL, cMet, EGFR) and non-RTKs (PYK2, FAK) signaling in TNBCEpithelial-Mesenchymal Transition (EMT) & TNBC metastasis
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Prof. Gil Levkowitz
hypothalamusDevelopmental neurobiologyMolecular neurophysiologyGeneticsNeuroendocrinology
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Prof. Moshe Oren
Role of p53 in tumor-host interactions.Collaboration with: Prof. Michal Lotem, Hadassah Medical Center Prof. Yinon Ben-Neriah, Hebrew University Medical SchoolGain of function of mutant p53 in cancer.Collaboration with: Prof. Varda Rotter, Weizmann Institute; Prof. Vassilis Gorgoulis, Athens University Medical SchoolMolecular biology of p53.Regulation of the Hippo pathway and its deregulation in cancerCrosstalk between the p53 and Hippo pathways
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Prof. Varda Rotter
Molecular mechanisms controlling the expression of p53 in normal cells and its deregulation in cancer cellsInvolvement of p53 in cell differentiation and apoptosis: <I>in vivo</I> and in vitro models.Cellular proteins that specifically complex with the p53 protein.Cellular proteins that are induced upstream or downstream to the p53 protein following genotoxic stress.
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Prof. Yardena Samuels
Synthetic lethal interaction network of melanomaIdentification of melanoma hub interactomesCRISPR screens to reveal driver gene interactions and drug resistance genesDecipher the immuno-genetic interactions between melanoma and T cellsHLA peptidome analysis of metastatic melanoma lesions
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Prof. Oren Schuldiner
A genetic dissection of developmental axon regenerationMolecular mechanisms of neuronal remodeling during development: Developmental axon pruning in DrosophilaThe role of cell-cell interaction in regulating developmental axon pruningThe role of intracellular signaling in regulating developmental axon pruningThe role of trafficking in regulating developmental axon pruningGlia and their effect on neuronal growth and remodeling
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Dr. Yonatan Stelzer
DNA methylation dynamics during cell fate decisionsEpigenetic reprogramming during gametogenesisMammalian parental imprinting as an epigenetic paradigmEnvironmental effects on the epigenomeEpigenetic perturbations in disease and cancer
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Dr. Ravid Straussman
Tumor microenvironment-mediated chemoresistanceTumor microbiomeEx-vivo Cultures of Tumor Tissues for Rapid Tailoring of Anti-Cancer TherapyPhenotypic and Mechanistic Characterization of Drug Tolerant Persister Cancer CellsSignalome: A Novel Approach for the Analysis of Signaling Pathway Activity in Cancer
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Dr. Itay Tirosh
Intra-tumor heterogeneity: combining computational and experimental approaches to understand the diversity of cells within tumors, their functions, interactions and clinical significance.Collaboration with: Mario Suva, Massachusetts General Hospital. Sid Puram, Washington University.Single cell analysis of clinical tumor samples, with a focus on gliomaComputational modeling of the tumor ecosystemTesting the function of tumor subpopulations in cell and animal models
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Prof. Eldad Tzahor
Head muscle patterning and differentiationCharacterization of head muscle derived satellite cellsDissecting the myogenic programs in head muscle progenitorsInvolvement of p53 in cranial myogenesisCardiac and skeletal muscle progenitors during vertebrate embryogenesisStudying the crosstalk between BMP and FGF signaling pathways in cardiac progenitorsRegulation of Islet1 gene expression using novel imaging techniques in live embryosThe origin of the heart endocardium: Focus on the role of endothelial cells in cardiogenesis
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Dr. Leeat Yankielowicz-Keren
MelanomaCollaboration with: Prof. Michal Lotem Prof. Eli Pikarsky Dr. Jonathan Cohen Prof. Yardena Samuels Prof. Steve Hodis Prof. Scott RodigImmunotherapyGraft verses host diseaseCollaboration with: Prof. Gerard SocieMultiplexed imagingCollaboration with: Dr. David van ValenArtificial intelligence
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Prof. Yehiel Zick
Mode of action of galectin-8, a mammalian lectinThe molecular basis of Insulin Resistance: a Phosphorylation based Uncoupling of Insulin SignallingThe insulin receptor as a model system for transmembrane signaling: Mode of interaction of the insulin receptor with its downstream effector molecules.Mammalian lectins as regulators of cell adhesion, cell growth, and apoptosis.Receptor trafficking: Regulation of endocytosis and recycling of the insulin receptor.Role of Galectin-8 in bone remodeling
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