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 which may drive cells towards differentiation or apoptosis. These studies, focusing on the mechanisms driving cells to 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-signals triggered by adhesive interactions. Of special interest are proteins such as b-catenin, which play a crucial role in reinforcing cell-cell adhesions and triggering gene expression.

U. Alon

Systems level analysis of gene regulation networks, with E. coli as a model system.

Combining theoretical, bioinformatic and experimental methods to discover design principles of genetic networks.

A. Amsterdam

Plasticity of gene expression during differenatiation in the gonads.

Crosstalk amond signals that control apoptosis.

Carcinogenesis in endocrine glands.

A. Ben-Ze'ev

The molecular basis of the role of cell-cell adhesion in malignant transformation: the b-catenin/APC case.

The dual role of b-catenin and plakoglobin in adhesion and transactivation: novel target genes activated by b-catenin and their role in oncogenesis.

The interplay between b-catenin signaling and p53-responsive pathways in the development of colon cancer.

A.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.

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.

B. Geiger

Molecular mechanisms of cell adhesion and motility in normal and cancerous cells.

Structure and signaling activity of cell-matrix and cell-cell adhesions.

Adhesion mediated regulation of cell growth, apoptosis and differentiation.

D. Ginsberg

Regulation of the activity of the E2Fs transcription factors.

E2F induced apoptosis and its modulation by Ras.

Repression of mitotic genes by E2F/RB complexes as part of the G2/M checkpoint.

E2F-dependent regulation of DNA repair genes.

Z. Kam

Cellular Biophysics

1. Computerized light microscopy, development of methods and applications to cellular and developmental biology.

2. Quantitative analysis of structural features and dynamic changes using computerized light microscopy. Lineage tracking in time-movies.

3. Neural network applied to analyze experimental data measurement of complex biological mechanisms, such as cell responses and signaling pathways, probed by genetic, molecular and morphological measurements.

U. Nudel

Structure, function and regulation of expression of the Duchenne muscular dystrophy (DMD) gene and its protein products in muscle and non-muscle cells. Prenatal diagnosis of DMD.

Dp71: the major product of the DMD gene in the brain and other non muscle tissues; analysis of possible involvement in development and in brain function by targeted gene inactivation.

The evolution of structure and function of the DMD gene and its products: Analysis in Drosophila and lower organisms.

Muscle differentiation in cell cultures - a model system for the study of cell commitment and regulation of tissue-specific gene expression. Genes determining the myogenic cell lineage (MyoD gene family and upstream genes) and their involvement in muscle cell differentiation.

M. Oren

Structure-function analysis of p53.

Relationship of p53 to programmed cell death.

Regulation of the Mdm2 oncoprotein

Role of p53 in senescence.

Regulation of proteins by phosphorylation, nitrosylation and acetylation.

Molecular biology of p63.

E. Peles

Molecular mechanisms of neuron-glia interactions.

Role of Caspr family members in neuronal development.

Cellular junctions of myelinated nerves.

Generation of specialized domains along myelinated axons.

Function of Caspr proteins in generating cell-cell contact in C. elegans.

V. Rotter

Molecular mechanisms controlling the expression of p53 in normal cells and its deregulation in cancer cells

1. Involvement of p53 in cell differentiation and apoptosis: in vivo and in vitro models.

2. Cellular proteins that specifically complex with the p53 protein.

3. Cellular proteins that are induced upstream or downstream to the p53 protein following genotoxic stress.

Y. Zick

The insulin receptor as a model system for transmembrane signaling: Mode of interaction of the insulin receptor with its downstream effector molecules.

Receptor trafficking: Regulation of endocytosis and recycling of the insulin receptor.

Mammalian lectins as regulators of cell adhesion, cell growth, and apoptosis.

A. Yayon

Fibroblast growth factors, their receptor tyrosine kinases and accessory heparan-sulfate proteoglycans as regulators of cell growth and differentiation.

Molecular modeling based mapping of ligand and receptor active sites and rational design of novel modulators for cancer and other human pathologies.

Molecular understanding of Achondroplasia and other human inherited skeletal disorders caused by specific mutations in FGF receptors.

D. Zipori

Regulation of normal cell differentiation and tumor cell growth by the hemopoietic microenvironment

1. Stem cell growth and the organ stroma.

2. Characterization of the cytokine antagonist, Activin A; signal transduction and biological functions.

3. PSF, a pre mRNA splicing factor involved in processes of differentiation in stem cell systems.

 This file was last modified on 08/15/2004 15:13:56

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