Department of Molecular Cell Biology
Yehiel Zick, Head
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.
Systems level analysis of gene regulation networks, with E. coli as a model system.
Combining theoretical and experimental methods to discover design principles of biological circuits
Systems Immunology
U. Alon, Nir FriedmanEvolution
A. Amsterdam
Plasticity of gene expression during differenatiation in the gonads.
Crosstalk amond signals that control apoptosis.
Carcinogenesis in endocrine glands.
The interplay between the role of β-catenin in cell adhesion and signaling during colon cancer development.
The role of novel β-catenin target genes in tumor development and metastasis
The molecular basis and signaling roles of nerve cell adhesion receptors in colon cancer metastasis
Epithelial-mesenchymal transition (EMT), cancer stem cells (CSCs) and Wnt target genes in colon cancer metastasis
A. 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.
E. 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.
Molecular diversity of adhesion complexes
The roles of mechanical force in adhesion development
Role of phosphorylation in regulating cell adhesion and migration
Signaling from the ECM
Cell adhesion and migration in cancer
Quantitatibve automated microscopy and high throughput screens
Design Principles of mammalian tissues
Combining mathematical models and sensitive single-molecule measurements to study how single cells interact in tissues to jointly bring about physiological goals
Cellular Biophysics
Z. Kam, Benjamin Geiger, John Sedat, David Agard (UCSF)
- Quantitative analysis of structural features and dynamic changes in cells using microscope imaging
- High throughput high-definition microscopy application in systems cell biology
- Adaptive optics methods applied to thick sample imaging
- Cell level informatics
The role of cellular senescence in human disease
Mechanisms of interaction of senescent cells with their microenvironment
Cellular senescence in cancer development and treatment
Breast cancer progression and metastasis.
- Signal transduction therapy for triple negative breast cancer (TNBC).
- PYK2 and FAK as potential therapeutic targets for breast cancer metastasis.
- Chemotherapy resistance and recurrence of breast cancer.
Developmental neurobiology
hypothalamus
Molecular neurophysiology
Genetics
Neuroendocrinology
Molecular biology of p53.
Regulation of proteins by covalent modifications.
Role of microRNAs in cancer.
Relationship of p53 to programmed cell death.
Gain of function of mutant p53 in cancer.
M. Oren, Prof. Varda Rotter, Weizmann Institute; Prof. Vassilis Gorgoulis, Athens University Medical SchoolRole of p53 in tumor-host interactions.
M. Oren, Dr. Jair Bar, Sheba Medical CenterRegulation of the Mdm2 oncoprotein.
M. Oren, Prof. Yossi Shilo, Tel Aviv UniversityHistone ubiquitylation in regulation of gene expression and in cancer.
M. Oren, Prof. Yossi Shiloh, Tel Aviv University, Prof. Robert Roeder, Rockefeller University; Prof. Steven Johnsen, Goettingen University; Dr. Itay Ben-Porath, HUJICellular junctions of myelinated nerves.
Role of Caspr family members in neuronal development.
Generation of specialized domains along myelinated axons.
Function of Caspr proteins in generating cell-cell contact in C. elegans.
Molecular mechanisms of neuron-glia interactions.
Molecular mechanisms controlling the expression of p53 in normal cells and its deregulation in cancer cells
- Involvement of p53 in cell differentiation and apoptosis: in vivo 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.
Molecular mechanisms of neuronal remodeling during development: Developmental axon pruning in Drosophila
- The role of cell-cell interaction in regulating developmental axon pruning
- The role of intracellular signaling in regulating developmental axon pruning
- The role of trafficking in regulating developmental axon pruning
- Glia and their effect on neuronal growth and remodeling
A genetic dissection of developmental axon regeneration
Head muscle patterning and differentiation
- Characterization of head muscle derived satellite cells
- Dissecting the myogenic programs in head muscle progenitors
- Involvement of p53 in cranial myogenesis
Cardiac and skeletal muscle progenitors during vertebrate embryogenesis
- Studying the crosstalk between BMP and FGF signaling pathways in cardiac progenitors
- Regulation of Islet1 gene expression using novel imaging techniques in live embryos
- The origin of the heart endocardium: Focus on the role of endothelial cells in cardiogenesis
Receptor trafficking: Regulation of endocytosis and recycling of the insulin receptor.
Mammalian lectins as regulators of cell adhesion, cell growth, and apoptosis.
The insulin receptor as a model system for transmembrane signaling: Mode of interaction of the insulin receptor with its downstream effector molecules.
The molecular basis of Insulin Resistance: a Phosphorylation based Uncoupling of Insulin Signalling
Mode of action of galectin-8, a mammalian lectin
Role of Galectin-8 in bone remodeling