Varda Rotter, Head (until October 2010)
The Norman and Helen Asher Professorial Chair of Cancer Research
Elior Peles, Head (from November 2010)
The Hanna Hertz Professorial Chair for Multiple Sclerosis and Neuroscience
Research in our Department focuses on understanding the molecular mechanisms and systems levels that control cell behavior:
- growth regulation
- determination of cell fate and differentiation
- cell adhesion and movement
- intracellular trafficking
- These studies include investigations into the mode of action of growth factors, and the nature of signals triggered by them in target cells. Cell growth regulation is also examined through explorations of tumor suppressor genes, such as p53, which inhibit cell proliferation and can drive cells toward differentiation or apoptosis, as well as through the characterization of growth-activating genes and signaling networks.
- Our researchers also address the understanding of the mechanisms underlying cancerous transformation, either due to deregulated growth or to failure to undergo apoptosis. Advanced gene screening techniques and genetically modified experimental models are used to identify and characterize specific genes that are involved in normal and malignant growth. There is broad interest in the molecular mechanisms of cell adhesion and motility, and their involvement in the regulation of cellular and embryonic morphogenesis, neuronal development, and in the spread of tumor metastases. Of special interest are proteins such as §-catenin, which plays a critical role in reinforcing cell-cell adhesions, as well as triggering gene expression. These studies include characterizing the mechanisms underlying adhesive interactions, the role of sugars in adhesive processes. Furthermore we investigate the identification of recognition molecules which mediate cell-cell interactions during nervous system development. Understanding of the process by which surface-associated adhesion molecules enable the cell to bind to the cytoskeleton, and the involvement of such adhesions in cell motility and signaling is thoroughly investigated.
- Other interesting issues studied in our Department are concerned with developmental biology, and differentiation, processes are dealt with by using cutting edge technologies. This includes also the molecular genetics and evolution of genes involved in human diseases and myogenesis as a model system for investigating possible therapeutic potentials.
- To understand the behavior of cells, it is important to add to the molecular level of description an understanding on the level of systems biology. For this purpose, study of model organisms such as E. coli are useful for defining the design principles of biological circuits. Combined experimental and theoretical approaches allow one to define basic network motifs and their functions, as well as studying the role of evolution in shaping regulatory circuits in the cell.
- Since these cellular processes involve groups of interacting factors, we are also interested in mathematical modeling and computational analysis of biochemical and gene circuitry in normal cells and their deregulation in cancer.
Uri Alon focuses on the cell-wide analysis of protein activity, and how cells make decisions and process information. A systems biologist working to develop a "blueprint" of a living cell, he has determined that the biochemical circuitry in the cell is composed of repeating circuit patterns called network motifs, each of which performs a specific information-processing task.
Abraham Amsterdam focuses on investigating the control of ovulation and factors, which may explain the risk factors for ovarian cancer. We used ovarian transcriptsomes as a tool for global approach of genes, modulated by gonadotropic hormones in human ovarian granulosa cells. Combined studies by DNA microarrays, biochemical and physiological approaches revealed that epiregulin (Ep) and amphiregulin (Ar), members of the mitogenic epidermal growth factor (EGF), are highly expressed on the level of the genes and the proteins, following gonadotropin stimulation. In contrast, in ovarian cancer, these EGF like factors are expressed constitutively. Avri Ben-Ze’ev studies the genes and cellular mechanisms involved in cancer. In focusing on β-catenin, a gene that is abnormally activated in colorectal and many other types of cancer, he has clarified the consequences of β-catenin hyperactivation in cancerous cells, and identified some of the signals unleashed by this gene in instances of malignancy.
Alexander Bershadsky studies how cells move, and the physical forces necessary for cells to attach themselves to the substrate and to one another. In exploring the points of contact, which act as mechanical "sensors" that provide the cell with information about its environment and determine its behavior, he has learned that in cancer cells, the activity of these "sensors" is disrupted, which likely accounts for the cell's difficulty in adhering to substrates and, consequently, their greater mobility. Eli Canaani iinvestigates the MLL gene and its protein products, in order to understand their biochemical activities and the mechanism by which they trigger leukemia. Leukemias associated with rearrangement of the MLL gene account for the majority of acute lymphocytic and myelocytic leukemias in infants, and in therapy-related leukemias. Benjamin Geiger focuses mainly on the mechanisms responsible for communication between cells, both normal and cancerous. He is attempting to identify and trace the specific molecular involved in intercellular recognition and communication, and to investigate the molecules and signaling processes which mediate such interactions.
David Givol investigates the tumor suppressor gene p53, the most frequently mutated gene in all cancers, and focuses on mechanisms that activate p53 and the way p53 activates target genes, using microarrays. He also studies the effect of p53 on different chemotherapies. Recently he has been studying connection between stem cells and cancer, exploring the properties of "cancer stem cells" that are responsible for the propagation of malignant tumors. He isolates such stem cells from leukemia and glioblastoma and compares gene expression profiles of stem and non-stem tumor cells and test differential drug response in these cells.
Zvi Kam is developing and applying high-resolution automated cell-based screening microscopy for functional analysis of cells. Multiple perturbations by compound libraries and by siRNA are applied to reporter cells cultured in multi-well plates, cell images are recorded, and quantitative image analysis scores the responses. This high-throughput platform provides systems biological experimental approach for studying complex cellular mechanisms.
Sima Lev studies the molecular mechanisms of membrane trafficking pathways in mammalian cells. These pathways mediate the transport of proteins, lipids, and sugars to their final cellular destinations and are fundamental to normal cell function and survival. Defects in these pathways are associated with many human diseases and can affect cell cycle progression. She is currently focusing on mechanisms that control the lipid composition of membrane domains along the secretory pathway, as well as the regulation of membrane trafficking events during cell division.
Gil Levkowitz utilizes zebrafish embryos as a vertebrate model organism to investigate how coordinated development of multiple neuronal types is achieved in the brain. The lab studies the development and maintenance of dopaminergic neurons and of several neuropeptides- secreting neurons, which reside in the hypothalamus. Understanding these processes is relevant to prospective therapies for neurological disorders as aberrant development of the dopaminergic system might be a major factor contributing to Parkinson’s disease and impairments in hypothalamic neurons are associated with defects in energy balance, and in neuro-endocrine and psychiatric disorders.
Moshe Oren is studying the regulation of the p53 tumor suppressor and its relevance to cancer. Specific interests include the analysis of signal transduction pathways that modulate p53 activity in response to various stress signals, exploration of the molecular basis for the ability of p53 to elicit different cell fate changes in response to different triggers, the role of p53 in the interaction between tumor cells and their microenvironment, and (in collaboration with V. Rotter) the analysis of gain of function activities of cancer-associated p53 mutants. In addition, the group is studying the regulation and function of the Mdm2 oncoprotein, a major component of the p53 network.
Elior Peles focuses on the biology of Schwann cells and oligodendrocytes, the myelinating glial cells of the peripheral and central nervous system, respectively. His group is studying how these cells recognize and wrap axon with myelin, an insulating lipid membrane that enables the rapid and efficient conduction of nerve impulses. His laboratory is also studying how axon-glia interaction control the molecular organization of the axonal membrane, which is required for the normal function of myelinated nerves and is disturbed in Multiple Sclerosis, as well as in a wide range of other neurological diseases. Varda Rotter focuses on the p53 gene, which as a wild type protein plays a pivotal role in protecting cells from becoming cancerous, but when mutated or inactivated causes the accumulation of genetic instabilities, which in turn induces malignant transformation of cells. On the question of mutant p53 gain of function, which is central in her research, she is collaborating with Moshe Oren and Eytan Domany. As it is well accepted that malignant transformation is a stepwise process involving various defined gene signatures it is the challenge of her studies to discover which of these gene networks involve the p53 protein.
Oren Schuldiner studies the molecular mechanism of neuronal remodeling. His lab uses the fruit fly as a model to investigate axon pruning. Using sophisticated genetic and microscopic tools to create and visualize a single mutant neuron in a heterozygous brain, it is possible to study cell autonomous processes that occur late during development in vivo. To understand the mechanisms that regulate axon pruning, his lab focuses finding and characterizing novel proteins that play a role in cell-cell interactions (specifically neuron-glia interactions), cargo trafficking, and signaling within the neurons. His lab also studies the molecular switch that induces re-growth of the axons following pruning. Axon fragmentation during pruning shares molecular similarities with processes occurring in neurodegenerative diseases. Therefore, uncovering the molecular mechanisms underlying pruning and axon re-growth will promote our understanding of axon fragmentation and regeneration during development and disease.
Eran Segal develops computational models aimed at understanding how biological processes are regulated at various levels. These include models that integrate transcription factors and DNA sequences, aimed at explaining how complex patterns of gene expression are encoded in DNA sequences and read by cells, and sequence-based models for chromatin structure that explain how nucleosomes get positioned on genomes and how they consequently affect gene expression.
Uri Nudel and David Yaffe are investigating the structure, evolution and function of products of the dystrophin gene, which is defective in Duchenne muscular dystrophy (DMD). Gene inactivation techniques were used to study the function of Dp71, the major non-muscle product of the DMD gene, and its possible involvement in development and in learning capacity. Cloning and analysis of the homologous genes from sea urchin and drosophila have important implications with regard to the evolution of the DMD gene family and function of the DMD gene products. These studies showed a very impressive conservation during evolution of the structure of the DMD gene and its multiple products. Functional studies indicated a number of abnormalities associated with mutants of the drosphila orthologue of the DMD gene, including defects in learning capacity. It is interesting to note that in humans, DMD is also often associated with cognitive impairments. Dr. Rachel Sarig, of the same group is also investigating the topic of adult stem cells and their potential application for cell therapy. Recent studies have indicated the prevalence and importance of adult stem cells in development, maintenance and regeneration of various tissues. Muscle progenitor cells are of special interest as an excellent, easy accessible cell type, with well-characterized markers and transcription factors associated with its various differentiation stages, thus offering a convenient model system. The team has isolated, from mouse skeletal muscle a population of slow adherent myogenic cells that can proliferate for extended periods, as suspended clusters of cells (myospheres). Myosphere cells express myogenic markers, and differentiate to muscle fibers both in vitro and in vivo. Cloned populations of these cells and of human myogenic cells are being examined for their plasticity and ability to transdifferentiate into other cell lineages. Preliminary results suggest that these cells can be reprogrammed into neuronal cells. Yehiel Zick studies the molecular basis of insulin resistance with a particular emphasis on the role of Ser/Thr kinases as negative-feedback regulators of this process. He also works to understand the activities of galectin-8, one of a family of animal lectins implicated in the development of prostate cancer. Demonstrating that galectin-8 as a modulator of cell cycle progression and as an inducer of cell growth arrest, he is working toward a novel, potentially curative treatment for prostate cancer. Dov Zipori focuses on the nature of the mesenchyme, primarily on the tendency of this tissue to generate cells in the stem state. Research in this laboratory is divided into three categories. The first is concerned with the molecular basis of stemness. The research team discovered that mesenchymal cells have promiscuous gene expression pattern in that they express genes of various lineage (e.g. T cell receptor components). The functional significance of this unexpected gene expression is a major subject for investigation in the laboratory. The second category relates to the regulation of stem cell self-renewal and differentiation. Previous studies of this research team suggested that the maintenance of the stem state is imposed by differentiation restraining molecules such as transforming growth factor β superfamily members. The group recently showed that Toll-like receptor ligands convey signals that block mesenchymal stem cell (MSC) differentiation. The generality of this phenomenon and its mechanism are now being studied. The third category relates to the practical use of MSC. These cells are used as a therapeutic modality in animal models for human diseases including osteoarthritis and multiple myeloma.
Research Staff, Visitors and Students
Uri Alon, Ph.D., Weizmann Institute of Science, Rehovot, Israel
Avri Ben-Ze'ev, Ph.D., The Hebrew University of Jerusalem, Jerusalem, Israel
The Samuel Lunenfeld-Reuben Kunin Professorial Chair of Genetics
Alexander D. Bershadsky, Ph.D., Cancer Research Center, Moscow, Russian Federation
The Joseph Moss Professorial Chair of Biomedical Research
Eli Canaani, Ph.D., University of California, Berkeley, United States
The Harry Kay Professorial Chair of Cancer Research
Benjamin Geiger, Ph.D., Weizmann Institute of Science, Rehovot, Israel
The Professor Erwin Neter Professorial Chair of Cell and Tumor Biology
Zvi Kam, Ph.D., Technion-Israel Institute of Technology, Haifa, Israel (on extension of service)
The Israel Pollak Professorial Chair of Biophysics
Moshe Oren, Ph.D., Weizmann Institute of Science, Rehovot, Israel
The Andre Lwoff Professorial Chair in Molecular Biology
Elior Peles, Ph.D., Weizmann Institute of Science, Rehovot, Israel
The Hanna Hertz Professorial Chair for Multiple Sclerosis and Neuroscience
Varda Rotter, Ph.D., Weizmann Institute of Science, Rehovot, Israel
The Norman and Helen Asher Professorial Chair of Cancer Research
Yehiel Zick, Ph.D., Weizmann Institute of Science, Rehovot, Israel
The Marte R. Gomez Professorial Chair of Photosynthesis
Abraham Amsterdam, Ph.D., The Hebrew University of Jerusalem, Jerusalem, Israel
David Givol, Ph.D., The Hebrew University of Jerusalem, Jerusalem, Israel
David Yaffe, Ph.D., The Hebrew University of Jerusalem, Jerusalem, Israel
Sima Lev, Ph.D., Weizmann Institute of Science, Rehovot, Israel
The Joyce and Ben B. Eisenberg Professorial Chair of Molecular Endocrinology and Cancer Research
Dov Zipori, Ph.D., Weizmann Institute of Science, Rehovot, Israel
The Joe and Celia Weinstein Professorial Chair
Valery Krizhanovsky, Ph.D., The Hebrew University of Jerusalem, Jerusalem, Israel
Yigal Allon Fellow
Incumbent of the Carl and Frances Korn Career Development Chair in the Life Sciences
Gil Levkowitz, Ph.D., Weizmann Institute of Science, Rehovot, Israel
Incumbent of the Tauro Career Development Chair in Biomedical Research
Oren Schuldiner, Ph.D., The Hebrew University of Jerusalem, Jerusalem, Israel
Incumbent of the Aser Rothstein Career Development Chair
Associate Staff Scientists
Janna Blechman, Ph.D., Moscow University, Moscow, Russian Federation
Anat Bren, Ph.D., Weizmann Institute of Science, Rehovot, Israel
Erez Dekel, Ph.D., Technion - Israel Institute of Technology, Haifa, Israel
Tatiana A. Rozovskaia, Ph.D., Institute of Molecular Biology, USSR Academy of Sciences, Moscow, Russian Federation
Assistant Staff Scientists
Yael Aylon, Ph.D., Tel Aviv University, Rehovot, Israel
Sigalit Boura-Halfon, Ph.D., Weizmann Institute of Science, Rehovot, Israel
Nancy Gavert, Ph.D., Weizmann Institute of Science, Rehovot, Israel
Irina Lavelin, Ph.D., The Hebrew University of Jerusalem, Jerusalem, Israel
Galia Maik-Rachline, Ph.D., Weizmann Institute of Science, Rehovot, Israel
Avi Mayo, Ph.D., The Hebrew University of Jerusalem, Jerusalem, Israel
Rachel Sarig, Ph.D., Weizmann Institute of Science, Rehovot, Israel
Junior Staff Scientist
Hila Rubin-Lifshitz, Ph.D., The Hebrew University of Jerusalem, Jerusalem, Israel (left May 2010)
Irina Issaeva Ph.D., Weizmann Institute of Science, Jerusalem, Israel (left November 2010)
Cellina Cohen-Saidon, Ph.D., Weizmann Institute of Science, Jerusalem, Israel (left July 2010)
Alexandra Lichtenstein, Ph.D., Ben-Gurion University of the Negev, Beer-Sheva, Israel
Ziv Porat, Ph.D., Weizmann Institute of Science, Rehovot, Israel
Alexander Sobko, Ph.D., Weizmann Institute of Science, Rehovot, Israel
Sabina Winograd-Katz, Ph.D., The Hebrew University of Jerusalem, Jerusalem, Israel
Yossi Buganim, Ph.D., Weizmann Institute of Science, Rehovot, Israel (left March 2010)
Ariel Cohen, Ph.D., Weizmann Institute of Science, Rehovot, Israel (left August 2010)
Yael Eshed Eisenbach, Ph.D., Weizmann Institute of Science, Rehovot, Israel
Konstantin Fineberg, Ph.D., Weizmann Institute of Science, Rehovot, Israel (left May 2010)
Eyal Kalo, Ph.D., Weizmann Institutue of Science, Rehovot, Israel (left June 2010)
Perry Stambolsky, Ph.D., Weizmann Institute of Science, Rehovot, Israel
Ronit Aloni-Grinstein, Institute for Biological Research (IIBR), Ness-Ziona, Israel
Milana Frenkel-Morgenstern (left September 2010)
Valery Krizhanovsky (left January 2010)
Helit Nabel-Rosen (left June 2010)
Guy Shinar, Dune Medical Devices Ltd., and Earlysense Ltd.,
Amos Simon, Sheba Hospital, Tel Hashomer, Israel
Fabian Anderegg, University of Zurich, Switzerland
Jozsef Baryani, INSERM E0021, Paris, France
Shai Garty, Max Planck Inst., Heildelberg, Germany
Dov Gefel, Barzilai Med. Ctr., Ashkelon, Israel
Anna Carla Goldberg
Marija Nika Lovsin, University of Ljubljana, Slovenia
Shmuel Rozenblatt, Tel-Aviv University , Israel
Sanford Sampson, Bar-Ilan University, Israel
Yardena Samuels, NIH, NIE, Bethesda, MD, U.S.A.
Tamar Shahal, Max Planck Inst., Stuttgart, Germany
David Sidransky, Johns Hopkins University , Baltimore, U.S.A.
Moshe Yaniv, Institut Pasteur, Paris, France
Shlomit Amar-Farkash, Hebrew University of Jerusalem, Israel
Liat Amir-Zilberstein, Ph.D., Weizmann Institute of Science, Israel
Vered Bar, Weizmann Institute of Science, Israel
Ran Brosh, Weizmann Institute of Science, Israel
Debora Rosa Bublik, Sissa-Isas
Ariel Cohen, Weizmann Institute of Science, Israel
Tomer Cooks, Tel-Aviv University, Israel
Yael Eshed-Eisenbach, Weizmann Institute of Science, Israel
Konstantin Feinberg, Weizmann Institute of Science, Israel
Shahar Frechter, Ph.D., Hebrew University of Jerusalem, Israel
Naama Geva-Zatorsky, Weizmann Institute of Science, Israel
Yaniv Hakim, Agriculture Faculty, Israel
Ido Horresh, Weizmann Institute of Science, Israel
Iris Kamer Samoelov, Weizmann Institute of Science, Israel
Elena Kartvelishvily, Ph.D., Technion - Israel Institute of Technology, Israel
Ira Kogan-Sakin, Weizmann Institute of Science, Israel
Daniel Koster, Ph.D., Delft University of Technology
Orly Laufman, Weizmann Institute of Science, Israel
Julieta Leyt Kachanovsky, Ph.D., Hebrew University of Jerusalem, Israel
Efrat Lidor Nili, Weizmann Institute of Science, Israel
Ariel Livne, Hebrew University of Jerusalem, Israel
Merav Marom, Hebrew University of Jerusalem, Israel
Neta Moskovits, Weizmann Institute of Science, Israel
Lior Noy, Weizmann Institute of Science, Israel
Meirav Pevsner-Fischer, Weizmann Institute of Science, Israel
Ziv Porat, Weizmann Institute of Science, Israel
Nadya Rakovitsky, Bar-Ilan University, Israel
Adriana Reuveny, Ph.D., Weizmann Institute of Science, Israel
Ruth Scherz-Shouval, Ph.D., Weizmann Institute of Science, Israel
Tamar Shahal, University of Cambridge
Tom Shemesh, Tel-Aviv University, Israel
Guy Shinar, Weizmann Institute of Science, Israel
Alessia Vivanti, University of Rome
Hyun-Jeong Yang, Tokyo Institute of Technology
Shirit Yaniv, Technion - Israel Institute of Technology, Israel
Yuliya Zilberman, Weizmann Institute of Science, Israel
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