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Edgar Pick is an Israeli immunologist who is Professor Emeritus of Immunology in the Department of Clinical Microbiology and Immunology at the Faculty of Medicine at Tel Aviv University, [1] Israel.
Pick was born in 1938 in Lugoj, Romania. After receiving his baccalaureate at the Coriolan Brediceanu High School in Lugoj, he enrolled at the Victor Babeș University of Medicine and Pharmacy. [2] He completed his medical studies at the Hebrew University Hadassah Medical School in Jerusalem, [3] graduating with an M.D. in 1965. He was a postdoctoral fellow in experimental pathology at the Scripps Clinic and Research Foundation in La Jolla, California, from 1965 to 1967, where he trained with Joseph D. Feldman. [4] In 1967 he joined the laboratory of John L.Turk, the world leader of cell-mediated immunity studies. [5] He received a Ph.D. from the University of London in 1970. While in London, Pick focused on the study of soluble products made by antigen-stimulated T lymphocytes—known as lymphokines, and later as a form of cytokines—characterizing molecules known as "skin reactive factor" [6] and "migration inhibitory factor". [7] With Turk, he published one of the first reviews on lymphokines. [8]
In October 1970, Pick was appointed Senior Lecturer of Immunology in the Department of Human Microbiology (now Clinical Microbiology and Immunology) at the Sackler Faculty of Medicine, Tel Aviv University, and rose to professorship in 1979. His research centered on the role of T cell-derived lymphokines in enhancing innate immunity by augmenting the capacity of phagocytes to produce reactive oxygen species (ROS) in response to pathogenic microorganisms. [9] He co-edited the first book on lymphokines, [10] and edited the 15 volumes of the series Lymphokines. [11]
Pick is best known for his fundamental studies on the enzyme complex responsible for the generation of the primary ROS, superoxide, by phagocytes, known as the NADPH oxidase. With Yael Bromberg, he described a novel method of activating the NADPH oxidase derived from resting phagocytes by unsaturated fatty acids [12] and anionic amphiphiles, [13] known as the "cell-free system". [14] This approach was a major paradigm shift, leading to the discovery that phagocytes contain, in addition to the membrane component directly responsible for superoxide production (known as gp91phox or Nox2), cytosolic components, responsible for the formation of the active NADPH oxidase complex. It also led to the identification of previously unknown causes for an inherited disease, characterized by the inability of phagocytes to produce ROS, known as Chronic Granulomatous Disease, resulting in repeated infections. Pick (with D. Sha’ag and T. Kroizman) also had a leading role in the identification and characterization of the "cytosolic components" of the NADPH oxidase, [15] [16] and is best known for the finding (with A. Abo and A.W. Segal) that the small GTPase Rac is an essential participant in the activation of the NADPH oxidase. [17] [18] [19] This discovery had wide-ranging implications for the understanding of the pathogenesis and treatment of diseases caused by excessive production of ROS, and for new applications of statin drugs.
Pick's other major contribution (with G. Joseph and I. Dahan) was introducing "peptide walking" as a method to identify functionally important regions in individual NADPH oxidase components [20] [21] and as a path to the discovery of peptide-based drugs for the treatment of diseases caused by excessive generation of ROS. [22]
Pick is also known for the pioneering design (with Y. Berdichevsky and A. Mizrahi) of the tripartite chimeras ("trimeras"), where functionally important segments of the NADPH oxidase activating cytosolic components are fused in a single molecule; [23] [24] and for studies (with E. Bechor and A. Zahavi) on the mechanism of interaction of p67phox with Nox2. [25]
A description of Pick's contributions to NADPH oxidase research in a form accessible to the lay readership was recently published. [26] Pick has edited the book "NADPH Oxidases Revisited: From Function to Structure" .
Pick was the Incumbent of the Roberts-Guthman Chair in Immunopharmacology (1988-2008), Director of the J. F. Cohnheim – Minerva Center for Cellular and Molecular Phagocyte Research (1994-2008), Head of Sackler Institute of Molecular Medicine (1997-1998), and Head of Kodesz Institute of Host Defense against Infectious Diseases (1999-2008). [27]
He is a member of the American Society of Biochemistry and Molecular Biology, the American Association of Immunologists, the Society for Leukocyte Biology, the American Association for the Advancement of Science, and the Israel Immunological Society.[ citation needed ]. He became a Honorary Life Member of the Society of Leukocyte Biology in 2023 .
Pick was a member of the Editorial Boards of "International Archives of Allergy and Applied Immunology" (1974-1990), "Immunology" (1979-1986), "Cellular Immunology" (1984-1992), "Immunobiology" (1981-2003), "International Journal of Immunopharmacology" (1984-2000), "Journal of Leukocyte Biology" (1996-2001; Section Editor), and "FASEB Journal" (2006-2018). [28] He was a member of the advisory board of "Antioxidants" (2020). [29]
Pick's research has been supported by grants from institutions including the Israel Science Foundation, the US-Israel Binational Science Foundation, the National Institutes of Health, the German-Israeli Foundation for Scientific Research and Development, the Israel Cancer Research Fund, Deutsches Krebsforschungszentrum, and the Leukemia Research Foundation. He has been a regularly invited speaker and/or session chair at numerous international meetings, most notably the Gordon Research Conferences .
Pick published 113 peer-reviewed papers, 10 book chapters, and 19 papers published in Conference Proceedings. [30]
His papers were cited 11,775 times (till August 12, 2023), his h-index is 51, and his i10-index is 104. [31]
Chronic granulomatous disease (CGD), also known as Bridges–Good syndrome, chronic granulomatous disorder, and Quie syndrome, is a diverse group of hereditary diseases in which certain cells of the immune system have difficulty forming the reactive oxygen compounds used to kill certain ingested pathogens. This leads to the formation of granulomas in many organs. CGD affects about 1 in 200,000 people in the United States, with about 20 new cases diagnosed each year.
In chemistry and biology, reactive oxygen species (ROS) are highly reactive chemicals formed from diatomic oxygen (O2), water, and hydrogen peroxide. Some prominent ROS are hydroperoxide (O2H), superoxide (O2-), hydroxyl radical (OH.), and singlet oxygen. ROS are pervasive because they are readily produced from O2, which is abundant. ROS are important in many ways, both beneficial and otherwise. ROS function as signals, that turn on and off biological functions. They are intermediates in the redox behavior of O2, which is central to fuel cells. ROS are central to the photodegradation of organic pollutants in the atmosphere. Most often however, ROS are discussed in a biological context, ranging from their effects on aging and their role in causing dangerous genetic mutations.
Respiratory burst is the rapid release of the reactive oxygen species (ROS), superoxide anion and hydrogen peroxide, from different cell types.
In cell biology, a phagosome is a vesicle formed around a particle engulfed by a phagocyte via phagocytosis. Professional phagocytes include macrophages, neutrophils, and dendritic cells (DCs).
NADPH oxidase is a membrane-bound enzyme complex that faces the extracellular space. It can be found in the plasma membrane as well as in the membranes of phagosomes used by neutrophil white blood cells to engulf microorganisms. Human isoforms of the catalytic component of the complex include NOX1, NOX2, NOX3, NOX4, NOX5, DUOX1, and DUOX2.
NADPH oxidase 2 (Nox2), also known as cytochrome b(558) subunit beta or Cytochrome b-245 heavy chain, is a protein that in humans is encoded by the NOX2 gene. The protein is a superoxide generating enzyme which forms reactive oxygen species (ROS).
An alveolar macrophage, pulmonary macrophage, is a type of macrophage, a professional phagocyte, found in the airways and at the level of the alveoli in the lungs, but separated from their walls.
Apocynin, also known as acetovanillone, is a natural organic compound structurally related to vanillin. It has been isolated from a variety of plant sources and is being studied for its variety of pharmacological properties.
Voltage-gated proton channels are ion channels that have the unique property of opening with depolarization, but in a strongly pH-sensitive manner. The result is that these channels open only when the electrochemical gradient is outward, such that their opening will only allow protons to leave cells. Their function thus appears to be acid extrusion from cells.
Neutrophil cytosol factor 2 is a protein that in humans is encoded by the NCF2 gene.
Neutrophil cytosol factor 1, also known as p47phox, is a protein that in humans is encoded by the NCF1 gene.
NADPH oxidase 1 is an enzyme that in humans is encoded by the NOX1 gene.
Cytochrome b-245 light chain is a protein that in humans is encoded by the CYBA gene involved in superoxide production and phagocytosis.
RHO protein GDP dissociation inhibitor of Rho proteins regulates GDP/GTP exchange. The protein plays an important role in the activation of the oxygen superoxide-generating NADPH oxidase of phagocytes. This process requires the interaction of membrane-associated cytochrome b559 with 3 cytosolic components: p47-phox, p67-phox and a heterodimer of the small G-protein p21Rac1 and rho GDI. The association of p21rac and GDI inhibits dissociation of GDP from p21rac, thereby maintaining it in an inactive form. The proteins are attached via a lipid tail on p21rac that binds to the hydrophobic region of GDI. Dissociation of these proteins might be mediated by the release of lipids from membranes through the action of phospholipases. The lipids may then compete with the lipid tail on p21rac for the hydrophobic pocket on GDI.
Rac2 is a small signaling G protein, and is a member of the Rac subfamily of the family Rho family of GTPases. It is encoded by the gene RAC2.
Neutrophil cytosol factor 4 is a protein that in humans is encoded by the NCF4 gene.
Dual oxidase 1, also known as DUOX1 or ThOX1, is an enzyme which in humans is encoded by the DUOX1 gene. DUOX1 was first identified in the mammalian thyroid gland. In humans, two isoforms are found; hDUOX1 and hDUOX2. Human DUOX protein localization is not exclusive to thyroid tissue; hDUOX1 is prominent in airway epithelial cells and hDUOX2 in the salivary glands and gastrointestinal tract.
NADPH oxidase, EF-hand calcium binding domain 5, also known as NOX5, is a protein which in humans is encoded by the NOX5 gene.
NADPH oxidase organizer 1 is an enzyme that in humans is encoded by the NOXO1 gene.
p22phox Protein, also known as the human neutrophil cytochrome b light chain (CYBA), is an essential component of the membrane-associated enzyme phagocyte NADPH-oxidase This enzyme uses NADH or NADPH as the electron donor for the one electron reduction of oxygen to produce superoxide anion, a reactive oxygen species (ROS), and a functionally important step for the antimicrobial activity of phagocytic cells. p22phox is also expressed in many other human cells such as endothelial and vascular smooth muscle cells, including those within the coronary arteries. Specific polymorphisms of the CYBA gene have been identified that are associated with a decreased risk of coronary artery disease (CAD).
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