|Professor Irun R. Cohen|
The Helen and Morris Mauerberger Professor of Immunology
For Detailed Information, refer to Irun Cohen's Personal Web Page
DiaPep277 Peptide and Type 1 Diabetes
We study insulin dependent diabetes mellitus (IDDM) in NOD mice and in humans aimed at elucidating the role of autoimmunity to the 60kDa heat shock protein (hsp60) and other antigens. Mice transgenic for hsp60 on various promoters, peptide mapping of T-cell antigens, cytokines produced by pathogenic T cells, and analysis of antibody isotypes are among the methods used. We have discovered how to arrest the autoimmune pathogenic reaction by administering a defined hsp60 peptide. The peptide induces a shift in the autoimmune phenotype which causes regression of the autoimmune inflammatory reaction. Clinical trials of hsp60 peptide therapy are underway in humans.
Innate Immune Receptors and hsp60
The hsp60 molecule is known to be a molecular chaperone that is up-regulated in response to stress. We now know that hsp60 also functions to activate cells of the immune system by serving as a ligand for innate toll-like receptors. We are studying the interactions of hsp60 and its peptide epitopes with these receptors on macrophages and T-cells, and the resultant effects on regulation of immune responses.
Regulation of Pro-inflammatory Cytokines by Natural Disaccharide Molecules
Together with Dr. Ofer Lider, we have discovered that the T-cell inflammatory response involves the action of a heparanase enzyme that degrades the heparan sulfate moiety of the extracellular matrix. Among the products of heparanase action are disaccharide molecules that exert feed-back inhibition of the pro-inflammatory cytokine cascade (TNF). We are studying the disaccharide receptor, the intracellular signals transduced and the regulation of TNF expression in T cells and macrophages. Clinical trials are being planned to apply the disaccharide to the regulation of inflammatory diseases in humans.
Heat shock protein molecules such as hsp60 are hyper-expressed at any site of inflammation; thus hsp60 expression is a universal feature of any infection. The hsp60 molecule is also the target of naturally autoimmune T cells in all individuals. This natural T-cell autoimmunity to hsp60 can be exploited, therefore, to construct subunit vaccines in which poorly immunogenic bacterial carbohydrate antigens are conjugated to defined peptides of hsp60. The hsp60 peptides serve as universal T-cell carrier epitopes that markedly enhance the efficacy of subunit vaccines. The immunology and applicability of such vaccines are being studied in bacterial infections.
Autoimmunity to the tumor suppressor molecule p53
The p53 molecule functions to regulate cell growth and mutated p53 is a regular feature of cancer cells. In collaboration with Prof. Varda Rotter of the Weizmann Institute we are studying immune responses to particular domains of p53, mutated or not, in the development of resistance to tumor growth based on p53 as a target of immune attack.
Modelling the Immune System
In collaboration with Prof. David Harel and Prof. Amir Pnueli of the Department of Applied Mathematics and Computer Science, we are developing new approaches (mostly bottom-up) to model the immune system. We aim to develop a language for computer simulation that is understandable to biologists.
An Antigen Chip: Immune bio-informatics
In collaboration with Prof. Eytan Domany of the Department of Physics of Complex Systems, we are developing a system for the global analysis of antibody and T-cell reactivities to an array of self-molecules. The aim is to investigate patterns of reactivities as a means to detect the state of the individual immune system in health and disease.
Liora Cahalon, PhD - Research associate
Michael Cohen - PhD student
Noam Cohen - Msc student
Na'aman Kam - PhD student jointly with David Harel
Hila Amir-Kroll, PhD – Post-doctoral fellow
Raanan Margalit - lab technician
Felix Mor, MD, PhD - Scientific Advisor
Honoch Otmi - lab technician (retired)
Merav Pevsner – PhD student, jointly with Dov Zipori
Yaki Setty – PhD student, jointly with David Harel
Ilya Sotnikov – PhD student
Ilan Volovitz - PhD student, jointly with Lea Eisenbach
Alexandra Zanin-Zhorov, PhD – Post-doctoral fellow