Yair Reisner, Head
The Henry H. Drake Professorial Chair of Immunology
The exponential growth of research activity in the life sciences has immunology in its center: The wide range of research activities in our Department covers a spectrum of studies in immunology ranging from fundamental aspects of antigen recognition and intracellular signaling to intercellular communication as well as immune-cell differentiation, migration and homing. Naturally, the progress made in resolving the basic principles underlining the mode of operation of the immune system is also applied to furthering the understanding of its disorders such as autoimmunity and allergies, as well as to the design of new immunotherapeutic modalities to fight cancer and infectious diseases.
Among the different interesting advances made during the recent years is the effective collaborations that have evolved amongst several researchers of the Department in studying the relationship between migration and adhesion of immune cells and their regulation during the functional maturation of the immune system.
The activities of the different research groups are briefly summarized below:
K. Abramson studies focus on a very unique population of the thymic stroma, called the medullary epithelial cells (MECs). Although these cells are extremely rare, they are absolutely essential for the establishment of immunological tolerance. This is due to their amazing capacity to express (and subsequently present) essentially all body antigens, including those whose expression was originally thought to be restricted only to peripheral organs (e.g. insulin, casein, etc). Hence, this "promiscuous" transcription of peripheral-tissue-antigen (PTA) genes in these unique cells "foreshadows" the self-antigens that T cells would encounter once they reach maturity and are released into the body. Many of these ectopic transcripts are regulated by the product of a single gene, the Autoimmune regulator (Aire), as mice with a mutation at this locus express only a fraction of the PTA repertoire. As a result, these animals develop antibodies and immune infiltrates directed at multiple peripheral tissues, resembling a multiorgan autoimmune disorder characteristic of humans with a mutated AIRE gene, the autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED). The lab aims at further delineation of the molecular and cellular mechanisms of the MEC-induced immunologic tolerance to self.
R. Alon's studies focus on the molecular basis and cellular mechanisms by which vascular adhesion molecules (selectins, integrins and their respective ligands) operate to capture and arrest circulating leukocytes on vascular endothelium under shear flow. The group investigates the crosstalk between these adhesion receptors and chemokine receptors on recruited leukocytes, facilitating their emigration to specific tissues both in normal and pathological immune processes. A major focus of the lab is the role of mechanical signals, transduced to adherent leukocytes by shear flow, and their function in the translation of biochemical signals from vascular endothelial cells into productive transendothelial leukocyte migration. Another focus is the interplay between endothelial and stromal transcribed chemokines in directing effector lymphocyte diapedesis. The group also investigates the roles of integrins and their ligands in leukocyte trafficking and function in inflamed lungs.
R. Arnon studies focus on antigenicity and vaccine development: Epitope-based synthetic vaccines; as well as autoimmune diseases: Experimental allergic encephalomyelitis, mechanisms of its suppression by basic copolymers of amino acids and relevance to multiple sclerosis (collaboration with M. Sela, R. Aharoni); Neurogenesis induced by copolymer I (with R. Aharoni); Exploitation of Copolymer I for additional application including inflammatory bowel diseases; Use of Cop1 in the prevention of transplant rejection (collaboration with M. Sela and R. Aharoni). In addition, she studies antigen-specific T-cells efficacy in cancer.
A. Ben-Nun demonstrated new primary target antigens (MOG, MOBP and OSP) in multiple sclerosis and their implications for pathogenic processes and immune-specific therapy; He studies multi-epitope/multi-antigen-directed, altered peptides-mediated, immune-specific therapy of 'complex EAE' associated with multiple pathogenic autoreactivities. The mechanisms of T cell modulation; T cell receptor and ligand interaction in autoimmune disease; Non-superantigenic bacterial toxins, T cell subsets and autoimmune diseases; Effect of encephalitogenic myelin-specific T cells and demyelinating antibodies on nerve conduction in the central nervous system in vitro and mechanisms of myelin/neuronal repair by adult stem cells.
G. Berke investigated the regulation of tumor immunity emphasizing tumor escape from immune attack. Along this line, he has addressed the regulation of expression and function of the death receptor Fas and its Ligand in tumors. He studied the binding to and activation of tumor specific T lymphocytes by tetrameric MHC – peptide complexes and showed direct activation of the lymphocytes by the bound tetramers. He developed a novel procedure to determine tumor cell susceptibility to anticancer drugs. Finally, he provided evidence that hypoxia predisposes the heart to myocardial damage induce by the death receptor Fas, a finding with implication to the mechanism of myocardial damage following myocardial infarction.
I.R. Cohen's research activities concentrate on the following topics: Autoimmune diabetes: Pathogenesis and clinical trials; Autoimmunity to hsp60 and the development of subunit vaccines against infectious diseases; Innate receptors for hsp60; Bio informatics: antigen chip (with Eytan Domany), modeling languages (with David Harel, Amir Pnueli), and T-cell repertoire chip; Regulation of immune inflammation by small carbohydrate molecules (originally done with Ofer Lider) and by lipoid molecules (with Meir Shinitzky);Autoimmunity to p53 and the development of systemic lupus erythematosus (with Varda Rotter).
L. Eisenbach: tumor progression results in the emergence of highly metastatic cells disseminating to distal organs. We are studying the interaction between malignant cells and the cellular immune system. In particular: a) Identification and characterization of human Tumor Associated Antigen (TAA) peptides derived from differentially expressed genes. Differentially expressed genes are discovered through genomic methods (DNA chips, SAGE) or molecular methods. TAAs from breast, colon, prostate and bladder tumors are the focus of our studies b) Design of anti-tumor peptide vaccines. c) Design of anti-angiogenic vaccines d) The role of interferon inducible genes in tumorigenesis e) Antigen presentation in tumor Immunity. f) Brain tumors (together with Prof. I. Cohen) g) Genetically manipulated tumor cell vaccines.
Z. Eshhar pursues the adoptive-gene and cell immunotherapy by redirecting effector (for cancer) and suppressor (for autoimmune diseases) T-cells using antibody based chimeric receptors and focusing on murine models of the human diseases. The process of homing, mode of action and fate of the genetically modified lymphocytes, as well as the optimal gene transfer procedure are studied and optimized. Another area of interest is the development of universal vaccine for allergy (together with Prof. G. Gross from Miga"l).
N. Friedman studies focus on network modules involved in T-cell activation and differentiation. Some questions of interest include - How does autoregulation effect thresholds for cell activation? What are the rules for combinatorial signaling, when a cell responds simultaneously to a number of cytokines? What roles are played by stochasticity in differentiation processes? We focus on experimental studies and theoretical modeling of processes mediated by cytokines during CD4 T cell activation and differentiation. We also develop and apply microfluidics devices for dynamic investigation of single cell responses in controlled microenvironments, using live cell imaging.
S. Fuchs studies immunoregulation of experimental autoimmune myasthenia gravis (EAMG) and the relation between myasthenia gravis and acetylcholine receptor (AChR); Structure, function and signal transduction of dopamine receptors and their presence in peripheral tissues in health and disease.
S. Jung investigates the in vivo origin and functional organization of the mononuclear phagocyte (MP) system, a body wide network of myeloid cells including macrophages and dendritic cells, as well as organ specific cell types such as the brain microglia. To study the differential functions of MP subsets in homeostasis and under pathogen challenge his research team uses the combined application of adoptive precursor cell transfers, imaging strategies and conditional in vivo cell ablation in the intact organism. A particular focus is given to the host/pathogen interface in the gut mucosa and the role of MPs in the maintenance of intestinal homeostasis as well as colitis development. More recently, the Jung laboratory developed a model system to investigate microglia functions in the healthy and diseased brain.
T. Lapidot T. Lapidot pursues the identification of cytokines, chemokines, stromal cells, proteolytic enzymes and adhesion molecules that mediate and regulate the migration and developmental program of human stem cells, both normal and leukemic, in a functional in vivo assay as well as the applications for human gene and cancer therapy. In particular, mechanistic insights into the pleotropic roles of the Chemokine SDF-1 and its receptor CXCR4 in stem cell migration (homing and mobilization) and retention in the stem cell niche as well as interactions between Osteoclasts and Osteoblasts in these processes are investigated.
O. Lider. Died, July 2004. His group's activities are being supervised by Prof. I. R. Cohen. Prof. Lider's students are continuing his studies on how the immune system operates under inflammatory conditions. They analyse the effects of cytokines on lymphocyte migration, cell surface adhesion receptor function. They also attempt to evaluate the enzymatic machinery required for leukocytes migration as well as examine the capacities of these enzymes to generate natural small molecular weight inhibitors of inflammation.
E. Mozes research focuses mainly on the mechanisms underlying the specific down-regulation of systemic lupus erythematosus (SLE) by a novel tolerogenic peptide (hCDR1) that is based on the sequence of the complementarity determining region-1 of a pathogenic autoantibody. The role of peptide induced regulatory T cells in the amelioration of disease manifestations, the significant effects of hCDR1 treatment on autoreactive T and B cell populations and on crucial signaling pathway, that are involved in SLE, are investigated. In addition, the potential therapeutic effects of hCDR1 on SLE patients are studied.
I. Pecht investigates the process of recognition performed by immunoreceptors and the mechanism of their signaling. Specifically, what is the physico-chemical nature of these receptors' stimuli how it is coupled to cellular responses and controlled. The model employed for the latter process is that of mast cell response by secretion of inflammatory mediators and its Fce receptor coupled cascade. T-cell antigen recognition is the main system where the immunological recognition processes are studied. Another, rather different problem investigated is the mechanism of internal electron transfer reactions in proteins.
Y. Reisner investigates a new approach for tolerance induction, using megadose stem-cell transplants to overcome MHC barriers in sublethally irradiated recipients; the mechanism(s) of tolerance induction by different tolerizing cells is investigated along the mechanism of a novel TCR independent T cell therapy directed against B cell malignancies ; also the reduced immunogenicity of human and pig embryonic tissues is investigated so as to afford a new source for organ transplantation.
I. Schechter scientific activities center on the active sites of enzymes and antibodies, mapping of the active site of proteases, the model of a large active site divided into subsites, rational design of inhibitors/drugs, proteases and inhibitors in biology and medicine, inhibitors can activate proteases to catalyze the synthesis of peptides, the binding energy of enzyme-inhibitor complex formation can be utilized to catalyze the synthesis of peptide bonds in the absence of an exogenous energy source (e.g. ATP), catalysis driven by binding energy may be relevant to prebiotic evolution since it is a simple system that enables synthesis, specificity and diversity.
M. Sela collaborates with R. Arnon on mechanism of action of copolymer 1,a drug against experimental allergic encephalomyelitis and multiple sclerosis. He collaborates also with Y. Yarden on monoclonal antibodies to ErbB1 and ErbB2,and their roles in potential anti-tumor strategy, as well as on aptamers specific for the respective epitopes. He also studies the immunotherapy of pancreatic cancer.
I. Shachar studies homing, maturation, survival and function of B cells in health and disease. Adaptive immunity depends on the production and maintenance of a pool of mature peripheral lymphocytes throughout life. Most of these cells circulate in the periphery in a quiescent state, without actively contributing to any given acute immune response. Thus, homing and survival are two essential mechanisms that regulate the maintenance of this peripheral lymphocyte pool. We follow these pathways in healthy cells and when things go wrong in tumor cells.
G. Shakhar studies cellular communication in the immune system with these objectives:
- Keeping biomedical applications in mind
*The lab addresses questions important for optimizing cancer immunotherapy: how tumor antigens are carried to draining lymph nodes, and how tumor cells evade destruction by infiltrating lymphocytes.
*The control of autoimmunity by Treg in inflammatory bowel disease.
- Observing complicated cellular networks - to be true to the complicated cellular milieu we follow interactions among multiple cell populations by using several channels simultaneously.
- Preserving physiological conditions - we image live mice using the least intrusive microscopic methods to keep blood, lymph and neural connections intact.
- Employing cutting-edge microscopic techniques - we use two-photon fluorescent microscopy and second harmonics generation, which are ideal for in vivo microscopy.
Research Staff, Visitors and Students
Ronen Alon, Ph.D., Weizmann Institute of Science, Rehovot, Israel
The Linda Jacobs Professorial Chair in Immune and Stem Cell Research
Avi Ben-Nun, Ph.D., Weizmann Institute of Science, Rehovot, Israel
The Eugene and Marcia Applebaum Professorial Chair
Gideon Berke, Ph.D., Weizmann Institute of Science, Rehovot, Israel (on extension of service)
The Isaac and Elsa Bourla Professorial Chair of Cancer Research
Tsvee Lapidot, Ph.D., Weizmann Institute of Science, Rehovot, Israel
The Edith Arnoff Stein Professorial Chair in Stem Cell Research
Yair Reisner, Ph.D., Weizmann Institute of Science, Rehovot, Israel
The Henry H. Drake Professorial Professorial Chair of Immunology
Michael Sela, Ph.D., The Hebrew University of Jerusalem, Jerusalem, Israel
The W. Garfield Weston Professorial Chair of Immunology
Ruth Arnon, Ph.D., The Hebrew University of Jerusalem, Jerusalem, Israel
Irun R. Cohen, Ph.D., Northwestern University Medical School
Zelig Eshhar, Ph.D., Weizmann Institute of Science, Rehovot, Israel
Sara Fuchs, Ph.D., The Hebrew University of Jerusalem, Jerusalem, Israel
Nechama Haran-Ghera, Ph.D., The Hebrew University of Jerusalem, Jerusalem, Israel
Edna Mozes, Ph.D., Weizmann Institute of Science, Rehovot, Israel
Roald Nezlin, M.D., Academy of Medical Sciences, Moscow, Russian Federation
Israel Pecht, Ph.D., Weizmann Institute of Science, Rehovot, Israel
Israel Schechter, M.D., Ph.D., Weizmann Institute of Science, Rehovot, Israel
Lea Eisenbach, Ph.D., Weizmann Institute of Science, Rehovot, Israel
The Georg F. Duckwitz Professorial Chair of Cancer Research
Steffen Jung, Ph.D., Universitaet zu Koeln, Germany
Idit Shachar, Ph.D., Tel Aviv University, Tel Aviv, Israel
The Dr. Morton and Anne Kleiman Professorial Chair
Jakub Abramson, Ph.D., Weizmann Institute of Science, Rehovot, Israel
Incumbent of the Dr. Celia Zwillenberg-Fridman and Dr. Lutz Zwillenberg Career Development Chair
Nir Friedman, Ph.D., Weizmann Institute of Science, Rehovot, Israel
Incumbent of the Pauline Recanati Career Development Chair
Guy Shakhar, Ph.D., Tel Aviv University, Tel Aviv, Israel
Senior Staff Scientists
Rina Aharoni, Ph.D., Weizmann Institute of Science, Rehovot, Israel
Ruth Maron, Ph.D., Weizmann Institute of Science, Rehovot, Israel
Associate Staff Scientists
Tali Feferman, Ph.D., Macquarie University Sydney, Sydney, Australia
Sara Feigelson, Ph.D., Weizmann Institute of Science, Rehovot, Israel
Alexander Kalinkovich, Ph.D., Pirogov Moscow Medical Institute (PMMI), Russian Federation
Orit Kollet, Ph.D., Weizmann Institute of Science, Rehovot, Israel
Esther Lustig, Ph.D., Weizmann Institute of Science, Rehovot, Israel
Elias Shezen, Ph.D., Weizmann Institute of Science, Rehovot, Israel
Assistant Staff Scientists
Rina Falb, Ph.D., Tel Aviv University, Tel-Aviv, Israel
Shlomit Reich-Zeliger, Ph.D., Weizmann Institute of Science, Rehovot, Israel
Revital Aricha, Ph.D., Bar-Ilan University, Ramat-Gan, Israel
Shirly Becker Herman, Ph.D., Weizmann Institute of Science, Rehovot, Israel
Esther Witsch, Ph.D., Free University of Berlin, Berlin, Germany (left November 2010)
Nathali Kaushansky, Ph.D., Weizmann Institute of Science, Rehovot, Israel
Ravit Saada, Ph.D., Bar-Ilan University, Ramat-Gan, Israel
Esther Tzehoval, Ph.D., Weizmann Institute of Science, Rehovot, Israel
Alain Berrebi, Kaplan Medical Center, Rehovot
Sonia Berrih-Aknin, CNRC Hopital Marie Lannlongue, France (left February 2010)
Enrique Freud, Schneider Children's Medical Center, Petach-Tikva, Israel
Smadar Gertel, The Open University of Israel, Ra'anana, Israel
Valentin Grabovsky (deceased October 2010)
Debby Haite-Reuveni, The Open University of Israel, Ra'anana, Israel
David Margel (left June 2010)
Felix Mor, Rabin Medical Center, Petach-Tikva, Israel
Alexander Shtabsky, Tel Aviv University, Tel-Aviv, Israel (left July 2010)
Miriam Souroujon, Open University, Raanana, Israel (left March 2010)
Dalit Tchorsh (left July 2010)
Ilan Volovitz, Tel Aviv University, Tel-Aviv, Israel
Lior Zangi (left March 2010)
Ayelet Zauberman, The Israel Institute of Biological Research, Ness-Ziona
Benjamin Chain, University College London, UK
Ole Farver, Royal Danish School of Pharmacy, Copenhagen, Denmark
Nadav Haim, HLRZ, Julich, Germany
William Kerr, Suny at Stony Brook, NY, U.S.A.
Amit Maliar, Assaf Harofe Hospital, Zrifin, Israel
Ruth Maron, Harvard Med. School, MA, U.S.A.
Janos Roszik, University of Debrecen, Hungary
David Shafritz, A. Einstein College of Medicine, NY, U.S.A.
Yehuda Skornick, Ichilov Medical Ctr., Tel Aviv, Israel
Willem Van Eden, University of Utrecht, Nederland
Scot Wherland, University of Washington, Seattle, WA, U.S.A.
Einat Amit Romach, Agriculture Faculty, Israel
Yaron Antebi, Ph.D., Weizmann Institute of Science, Israel
Inbal Binsky-Ehrenreich, Weizmann Institute of Science, Israel
Shmuel Cohen, Hebrew University of Jerusalem, Israel
Hilah Gal, Ph.D., Weizmann Institute of Science, Israel
Georg Mahlknecht, Ph.D., Institute of Cell Biology (Now Bioanalytics)-Tum
Assaf Marcus, Weizmann Institute of Science, Israel
Alexander Mildner, Department For Neuropathology
Sigal Nakav, Ben-Gurion University, Israel
Wilfred Ndimongang Ndifon, Princeton University
Anita Sapoznikov, Weizmann Institute of Science, Israel
Amir Schajnovitz, Weizmann Institute of Science, Israel
Charlotte Servais, Ph.D., UniversitÉ Libre De Bruxelles
Ziv Shulman, Weizmann Institute of Science, Israel
Alona Telerman (Vishnevsk, Technion - Israel Institute of Technology, Israel
Nissan Yissachar, Bar-Ilan University, Israel
Simon Yona, Ph.D., University of London
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