Department of Pathology & Laboratory Medicine
Greg Retzinger, Ph.D., M.D.Pritzker School of Medicine, The University of Chicago, M.D., 1983 The University of Chicago, Ph.D., 1981
Of all the plasma proteins, fibrinogen, an adhesive protein and the precursor of the blood clot matrix, adsorbs preferentially to surfaces in contact with blood. Once bound, fibrinogen is predisposed to clot formation. A frequently observed consequence of this predisposition is the "clotting off" of circulatory prosthetics such as vascular grafts and heart valves. Thus, an aim of biomedical materials research is the synthesis of materials that do not bind fibrinogen in vivo. But fibrinogen does not adsorb to synthetic materials alone. Indeed, a host of naturally-occurring lipid surfaces -- both physiologic and pathophysiologic -- bind fibrinogen. Such surfaces include the cytoplasmic membrane of activated platelets and macrophages, the cytoplasmic membrane of tumor cells, the luminal face of atherosclerotic plaques, and even the cell wall of virulent tubercle bacilli. Once bound to these surfaces, fibrinogen is also predisposed to clot. By focusing clot formation on these surfaces, fibrinogen makes the surfaces adhesive. This fibrin-mediated adhesion operates during a number of important processes as seemingly unrelated as platelet plug formation, phagocytosis, metastasis and atherogenesis. Thus, by studying the interactions of fibrin(ogen) with surfaces, lipid surfaces in particular, some mechanistic insight might be gleaned relevant to the treatment of human disease.
Gregory Retzinger, Ph.D., M.D., has developed model systems with which to probe the role of lipid surfaces in the biologic processing of adsorbed fibrin(ogen). Dr. Retzinger's laboratory is now exploiting information derived from the study of these model systems to: 1) prepare a platelet analogue for use as a hemostatic agent, 2) develop an adjuvant for general use with vaccines, 3) formulate a method for delivering drugs to formed clots, and 4) inhibit tumor cell metastasis.
Recent Publications:
1. O'Connor SM, DeAnglis AP, Gehrke SH, Retzinger GS: Absorption of plasma proteins onto poly(ethylene oxide)/poly(propylene oxide) triblock copolymer films: a focus on fibrinogen. Biotechnol Appl Biochem 31:185-196, 2000.2. Mazzella FM, Retzinger GS, Acquired factor VIII
inhibitors. Clin Hematol 6:1-14, 2000.
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