Professor Emeritus
Ph.D. 1984
bio chemistry, alzheimer, cancer, brain, inflammation, neuro degeneration |
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- B.Sc. 1970-1973, Ben-Gurion University of the Negev, Beer Sheva - Biology (with honors). M.Sc. 1973-1975, Ben-Gurion University of the Negev, Beer Sheva - Biology (with honors). Advisor: Prof. A. Livne, Title of thesis: The effect of hashish components on blood platelets' functions. Ph.D. 1980-1984, Ben-Gurion University of the Negev, Beer Sheva – Biology Advisor: Prof. A. Livne, Title of thesis: Essential hypertension and its expression in erythrocyte membranes. B.Sc. 1970-1973, Ben-Gurion University of the Negev, Beer Sheva - Biology (with honors). M.Sc. 1973-1975, Ben-Gurion University of the Negev, Beer Sheva - Biology (with honors). Advisor: Prof. A. Livne, Title of thesis: The effect of hashish components on blood platelets' functions. Ph.D. 1980-1984, Ben-Gurion University of the Negev, Beer Sheva - Biology Advisor: Prof. A. Livne, Title of thesis: Essential hypertension and its expression in erythrocyte membranes.
- The research is devoted to host defense mechanisms against infections and inflammation. The production of superoxides by NADPH oxidase and proinflammatory lipid mediators by phospholipase A2 are of the most important functions for host defense. However, during altered physiological states, superoxides and lipid mediators may promote inflammatory reactions and participate in processes that lead to tissue injury and cause many diseases. The studies are focused on phagocyte cells, in particular neutrophil leukocytes, which are vital to defense against bacteria. Understanding the biochemical processes that regulate these functions is essential to control the activity of the cells during infection and inflammation, increase their ability of killing bacteria and prevent inflammation. Developing alternative therapeutic venues against infections and inflammation is of particular importance because of the limitation of future use in antibiotics. We have established a model of differentiated cytosolic PLA2-deficient PLB-985 cells that strongly implicates p85 cytosolic PLA2 (cPLA2) as the major PLA2 isozyme responsible for the activation of the NADPH oxidase complex, after its assembly, following stimulation of phagocytes. This study has a major contribution in demonstrating a role for arachidonic acid as a step in signal transduction. We have demonstrated that cPLA2 is transiently recruited to the plasma membranes by a functional NADPH oxidase in neutrophils. The association between these two enzymes provides the molecular basis for AA released by cPLA2 to activate the assembled NADPH oxidase. The ability of cPLA2 to regulate two different functions in the same cells (superoxide generation and eicosanoid production) is achieved by a novel dual subcellular localization of cPLA2 to different targets. Our present studies focus on the exact interaction sites between cPLA2 and NADPH oxidase and the target sites for the action of arachidonic acid release by cPLA2. Relaying on the results of basic research we are developing new therapeutic venues against infections and inflammation in animal models of inflammation, which seems to be very promising.
- Cytosolic phospholipase A2a in inflammatory diseases and cancer associated inflammation:
- Exploring its role in different processes in in vitro studies
- Exploring its role in various mouse models of inflammation with major emphasis on neuro- degeneration diseases: Alzheimer's Disease
Major expertise and techniques in the lab
- Signal transduction
- Phagocytic functions
- Mouse models of inflammation: colitis
- Collagen induced arthritis
Publications and funding summary / representative publications and grants
- Hadad, N., Tuval L., Elgazar-carmon, V., Levy R. and Levy R. Endothelial ICAM-1 protein induction is regulated by cytosolic phospholipase A2a via both NFkB and CREB transcription factors. J. Immunol. 186:1816-27, 2011.
- The Israel Science Foundation (ISF)
- Hagit Cohen - Animal behavioral studies Assaf Rudich – Neutropils and inflammation in initiating obesity
- Alon Friedman – Brain inflammation
Suggested multi-disciplinary research project / research focus topics
- Cross-talk of brain cPLA2a and PKC under stress and inflammation