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Edwin L. Cooper, Ph.D., Sc.D.
Professor, Laboratory of Comparative Immunology, Department of Neurobiology
David Geffen School Of Medicine at UCLA
Associate Member, Cousins Center for Psychoneuroimmunology, UCLA Neuropsychiatric Institute

Research Interests

My general research interests fall into several categories. First, immunobiology, second, comparative immunology with another subspecialization in invertebrate immunology. I have focused on an evolutionary approach in order to more fully understand the evolutionary basis for the origin and intricacies of the human immune system, including its cells, molecular products, and major organs (eg, tonsils). What has emerged is that the ancient immune systems of invertebrates more closely resemble the innate, natural, nonspecific non-clonal immune system of mammals including humans. The human immune system still depends upon its own "prehistoric" system but has evolved those characteristics that appeared later in fishes, amphibians, reptiles birds and mammals. This type of immune system is adaptive, induced, specific and


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clonal. The most highly significant conclusion and implication of invertebrate immune studies centers around the steadfast survival of invertebrates for millions of years despite the constant threat of extinction by microbial and neoplastic pathogens that destroy homeostasis. Clearly, if we could understand how invertebrates have managed this type of survival strategy, we might be able to design similar strategies to assist human survival in the face of infectious diseases often caused by microbes that are resistant to microbial flora. Since the protective system of importance is the immune system that guards against infectious pathogens, what better starting point to search for mechanisms of fighting pathogens than to examine long lived organisms, presumed relatives of extinct species? To understand major events in the development of immune competence, we have used several animal models: invertebrates (notably earthworms and tunicates, the latter group representing the protochordate ancestors of vertebrates including humans). Using cytofluorimetric analysis, microscopy, and mouse anti-human monoclonal antibodies, two types of leukocytes have been identified in earthworms: 1) small (8-11 µm) electron dense cells (SC) that stain by mAbs for epitopes present on human cell adhesion molecules (CD11a, CD45RA, CD45RO, CDw49b, CD54) and those for Beta 2-microglobulin and Thy-1; and 2) large (12-15 µm) electron lucent cells (LC) negative for these same markers; by serologic methods Beta 2-microglobulin had been previously demonstrated . Both cell types were negative for other CD and MHC class I and class II markers. Recently, we have extended this work showing that the small cells kill the tumor cell target K562 and that a component of the cytotoxic reaction may involve a primitive perforin molecule. The perforin gene transcript and its protein in the earthworm leukocytes has been analyzed utilizing immunohistochemistry, Western blot analysis and a mouse perforin antibody. RT-PCR and southern blot analysis were performed by perforin specific synthesizing primer and probe based on the human perforin cDNA sequence. Perforin antibody reacted with cytoplasmic granules in only small but not in large leukocytes. These cells also reacted with Thy-1 antibody. Molecular size of earthworm perforin analyzed by Western blot was about 70kDa. The perforin mRNAs from earthworm leukocytes, mouse spleen cells and human PBL revealed the same size which was identified by RT-PCR and southern blot analysis. These data indicated that perforin may be associated with earthworm leukocytes. The presence of a variety of molecules suggests that they have been conserved during evolution as common features of immune surveillance.

Publications

de Eguileor M, Tettamanti G, Grimaldi A, Boselli A, Scari G, Valvassori R, Cooper EL, Lanzavecchia G, Histopathological changes after induced injury in leeches., 1999, J Invertebr Pathol, 74, 14-28, Edition: 74

· Lange S, Kauschke E, Mohrig W, Cooper EL, Biochemical characteristics of Eiseniapore, a pore-forming protein in the coelomic fluid of earthworms., 1999, Eur J Biochem, 262, 547-56, Edition: 262

· Cikutovic MA, Fitzpatrick LC, Goven AJ, Venables BJ, Giggleman MA, Cooper EL, Wound healing in earthworms Lumbricus terrestris: a cellular-based biomarker for assessing sublethal chemical toxicity., 1999, Bull Environ Contam Toxicol, 62, 508-14, Edition: 62

· de Eguileor M, Grimaldi A, Tettamanti G, Valvassori R, Cooper EL, Lanzavecchia G, Different types of response to foreign antigens by leech leukocytes., 2000, Tissue Cell, 32, 40-48, Edition: 32

· de Eguileor M, Grimaldi A, Tettamanti G, Valvassori R, Cooper EL, Lanzavecchia G, Lipopolysaccharide-dependent induction of leech leukocytes that cross-react with vertebrate cellular differentiation markers., 2000, Tissue Cell, 32, 437-45, Edition: 32

· Kauschke E, Komiyama K, Moro I, Eue I, Konig S, Cooper EL, Evidence for perforin-like activity associated with earthworm leukocytes., 2001, Zoology, 32, 13-24, Edition: 32

· Kasahara S, Fugo H, Cooper EL, Wago H, Preliminary evidence of modulating Th1 cytokine after allergen challenge., 2001, Int J Immunopath Pharmacol, 14, 63-69, Edition: 14

· Kasahara S, Aizawa K, Okamiya M, Kazuno N, Mutoh S, Fugo H, Cooper EL, Wago H, UVB irradiation suppresses cytokine production and innate cellular immune functions in mice., 2001, Cytokine, 14, 104-11, Edition: 14

· Cabrera PV, Blanco G, Ernst G, Alvarez E, Cooper EL, Hajos S, Coelomocyte locomotion in the sipunculan Themiste petricola induced by exogenous and endogenous chemoattractants: role of a CD44-like antigen-HA interaction., 2002, J Invertebr Pathol, 79, 111-19, Edition: 79

· Engelmann P, Pal J, Berki T, Cooper EL, Nemeth P, Earthworm leukocytes react with different mammalian antigen-specific monoclonal antibodies., 2002, Zoology, 105, 257-65, Edition: 105

· de Eguileor M, Tettamanti G, Grimaldi A, Congiu T, Ferrarese R, Perletti G, Valvassori R, Cooper EL, Lanzavecchia G, Leeches: immune response, angiogenesis and biomedical applications., 2003, Curr Pharm Des, 2, 133-47, Edition: 2

· Koenig S, Wagner F, Kauschke E, Peter-Katalinic J, Cooper EL, Eue I, Mass spectrometric analyses of CL39, CL41 and H1,H2, H3 confirm identity with fetidin and lysenin produced by earthworm leukocytes., 2003, Dev Comp Immunol, 27, 513-20, Edition: 27

· Vazzana M, Cammarata M, Cooper EL, Parrinello N, Confinement stress in sea bass (Dicentrarchus labrax) depresses peritoneal leukocyte cytotoxicity., 2002, Aquaculture, 210, 231-43, Edition: 210

· Vojdani A, Pangborn JB, Vojdani E, Cooper EL, Infections, toxic chemicals and dietary peptides binding to lymphocyte receptors and tissue enzymes are major instigators of autoimmunity in autism., 2003, Int J Immunopathol Pharmacol, 16, 189-200, Edition: 16

· Grether GF, Kasahara S, Kolluru GR, Cooper EL, Sex-specific effects of carotenoid intake on the immunological response to allografts in guppies (Poecilia reticulata)., 2004, Proc R Soc Lond B, 271, 45-49, Edition: 271

· Wiesner L, Hahn ME, Karchner SI, Cooper EL, Kauschke E, Does an aryl hydrocarbon receptor (AHR)-like molecule exist in earthworms? Some implications for immunity., 2004, Pedobiologia, 47, 646-50, Edition: 47

· Cooper EL, Roch P, Earthworm immunity: a model of immune competence., 2004, Pedobiologia, 47, 676-88, Edition: 47

· Komiyama K, Okaue M, Miki Y, Ohkubo M, Moro I, Cooper EL, Non-specific cellular function of Eisenia fetida regulated by polycyclic aromatic hydrocarbons., 2004, Pedobiologia, 47, 717-23, Edition: 47

· Cooper EL, Parrinello N, Immunodefense in Tunicates: cells and molecules., 2001, The Biology of Ascidians, , 383-94.

Edwin L. Cooper, Ph.D., Sc.D.
Professor
Laboratory of Comparative Immunology
Department of Neurobiology
David Geffen School Of Medicine at UCLA
University of California, Los Angeles
Los Angeles California 90095-1763
Tel: (310) 825-9567; Fax: (310) 825-2224
email: [email protected]